Active subperiosteal versus passive subdural 24-hour drainage following single burr hole evacuation of chronic subdural haematoma (the SUPERDURA trial): protocol for a multicentre, randomised non-inferiority trial - PMC Skip to main content An official website of the United States government Here's how you know Here's how you know Official websites use .gov A .gov website belongs to an official government organization in the United States. Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites. Search Log in Dashboard Publications Account settings Log out Search… Search NCBI Primary site navigation Search Logged in as: Dashboard Publications Account settings Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide PERMALINK Copy As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice BMJ Open . 2026 Apr 15;16(4):e102410. doi: 10.1136/bmjopen-2025-102410 Search in PMC Search in PubMed View in NLM Catalog Add to search Active subperiosteal versus passive subdural 24-hour drainage following single burr hole evacuation of chronic subdural haematoma (the SUPERDURA trial): protocol for a multicentre, randomised non-inferiority trial Rares Miscov Rares Miscov 1 Department of Neurosurgery, Aalborg University Hospital, Aalborg, North Denmark Region, Denmark Find articles by Rares Miscov 1, ✉ , Mads Grønhøj Mads Grønhøj 2 Department of Neurosurgery, Odense University Hospital, Odense, Region Syddanmark, Denmark 3 BRIDGE - Brain Research Inter-DIsciplinary Guided Excellence, University of Southern Denmark Department of Clinical Research, Odense, Region Syddanmark, Denmark Find articles by Mads Grønhøj 2, 3 , Thorbjørn Søren Rønn Jensen Thorbjørn Søren Rønn Jensen 4 Department of Neurosurgery, Rigshospitalet, Copenhagen, Capital Region of Denmark, Denmark Find articles by Thorbjørn Søren Rønn Jensen 4 , Anders Emil Schack Anders Emil Schack 4 Department of Neurosurgery, Rigshospitalet, Copenhagen, Capital Region of Denmark, Denmark Find articles by Anders Emil Schack 4 , Anders Rosendal Korshoej Anders Rosendal Korshoej 5 Department of Neurosurgery, Aarhus University Hospital, Aarhus, Central Denmark Region, Denmark 6 Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Central Denmark Region, Denmark Find articles by Anders Rosendal Korshoej 5, 6 , Mette Haldrup Mette Haldrup 5 Department of Neurosurgery, Aarhus University Hospital, Aarhus, Central Denmark Region, Denmark 6 Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Central Denmark Region, Denmark Find articles by Mette Haldrup 5, 6 , Markus Harboe Olsen Markus Harboe Olsen 7 Depatment of Neuroanesthesiology, Rigshospitalet, Copenhagen, Capital Region of Denmark, Denmark 8 The Neuroscience Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Capital Region of Denmark, Denmark Find articles by Markus Harboe Olsen 7, 8 , Jacob Holmen Terkelsen Jacob Holmen Terkelsen 1 Department of Neurosurgery, Aalborg University Hospital, Aalborg, North Denmark Region, Denmark Find articles by Jacob Holmen Terkelsen 1 , Frantz Rom Poulsen Frantz Rom Poulsen 2 Department of Neurosurgery, Odense University Hospital, Odense, Region Syddanmark, Denmark 3 BRIDGE - Brain Research Inter-DIsciplinary Guided Excellence, University of Southern Denmark Department of Clinical Research, Odense, Region Syddanmark, Denmark Find articles by Frantz Rom Poulsen 2, 3 , Kaare Fugleholm Kaare Fugleholm 4 Department of Neurosurgery, Rigshospitalet, Copenhagen, Capital Region of Denmark, Denmark Find articles by Kaare Fugleholm 4 , Carsten Bjarkam Carsten Bjarkam 1 Department of Neurosurgery, Aalborg University Hospital, Aalborg, North Denmark Region, Denmark Find articles by Carsten Bjarkam 1 Author information Article notes Copyright and License information 1 Department of Neurosurgery, Aalborg University Hospital, Aalborg, North Denmark Region, Denmark 2 Department of Neurosurgery, Odense University Hospital, Odense, Region Syddanmark, Denmark 3 BRIDGE - Brain Research Inter-DIsciplinary Guided Excellence, University of Southern Denmark Department of Clinical Research, Odense, Region Syddanmark, Denmark 4 Department of Neurosurgery, Rigshospitalet, Copenhagen, Capital Region of Denmark, Denmark 5 Department of Neurosurgery, Aarhus University Hospital, Aarhus, Central Denmark Region, Denmark 6 Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Central Denmark Region, Denmark 7 Depatment of Neuroanesthesiology, Rigshospitalet, Copenhagen, Capital Region of Denmark, Denmark 8 The Neuroscience Center, Copenhagen University Hospital Rigshospitalet, Copenhagen, Capital Region of Denmark, Denmark ✉ Dr Rares Miscov; [email protected] None declared. Received 2025 Mar 18; Accepted 2026 Feb 24; Collection date 2026. Copyright © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/4.0/ . PMC Copyright notice PMCID: PMC13084802 PMID: 41985955 Abstract Introduction The main treatment of chronic subdural haematoma (CSDH) is neurosurgical evacuation with subsequent drainage. However, consensus on optimal drain modality and placement is lacking. Aim To examine whether 24-hour active subperiosteal drainage is non-inferior to 24-hour passive subdural drainage after a single burr hole evacuation of a symptomatic CSDH. Methods and analysis SUPERDURA is a multicentre randomised non-inferiority trial encompassing all neurosurgical units in Denmark. Adult patients with symptomatic CSDH admitted to a Danish neurosurgical unit for single burr hole evacuation will be screened for inclusion. Patients who are not able to give informed consent, and patients with recurrent CSDH, known cerebrospinal fluid abnormalities and other known brain pathologies will be excluded. Patients with bilateral CSDH will be registered as one case and treated similarly on both sides. Before surgical haematoma evacuation, patients will be randomised to 24-hour passive subdural drainage or 24-hour active subperiosteal drainage. The patients included and the two study statisticians will be blinded. The primary outcome is a composite outcome of 90-day mortality and symptomatic CSDH recurrence. Secondary outcomes are 90-day simplified modified Rankin score, 90-day serious adverse events and complications related to surgery or occurring during admission, including intracerebral haemorrhage due to misplaced drains, acute subdural haematoma, tension pneumocephalus, wound infection, drain seepage, subperiosteal haematoma, thromboembolic events, infections and seizures. A detailed statistical analysis plan is published separately. Sample size simulations of non-inferiority with a threshold of 7% increased relative risk show that a total of 354 participants will be required to demonstrate a relative risk reduction of recurrent CSDH and mortality of 30% for the cohort receiving active subperiosteal drainage given a stable power above 80% with an alpha of 5%. The study inclusion period is estimated to last 2 years. Ethics and dissemination Ethics approval for the inclusion of competent patients has been obtained from the North Denmark Region Committee on Health Research Ethics. Results of the primary and secondary outcomes will be submitted for publication in an international peer-reviewed journal and presented at relevant neurosurgical meetings. Trial registration number at ethics committee N-20240009, accepted 13 May 2024 and 13 December 2024. Trial registration number NCT06621407 . Keywords: NEUROSURGERY, STATISTICS & RESEARCH METHODS, Randomized Controlled Trial STRENGTHS AND LIMITATIONS OF THIS STUDY. SUPERDURA is a multicentre randomised trial designed to evaluate non-inferiority of 24-hour active subperiosteal drainage concerning a composite outcome of 90-day mortality and recurrence to 24-hour passive subdural drainage following evacuation of symptomatic chronic subdural haematoma (CSDH). National standardised CSDH management in Denmark will ensure high data quality. Limitations are the inability to blind the treating surgeons and nurses, and the lack of inclusion of incapacitated patients. Introduction The incidence of chronic subdural haematoma (CSDH) is increasing due to an ageing population. 1 , 4 The surgical treatment of symptomatic CSDH is haematoma evacuation followed by drain placement to facilitate postoperative drainage. 5 6 No international consensus exists on drain placement (subdural or subperiosteal), and drainage method (time, active vs passive drainage). 5 , 8 In Denmark, CSDH is surgically treated in four neurosurgical departments using a standardised treatment protocol, 9 , 12 enabling two recent larger prospective national multicentre trials evaluating the optimal postoperative drainage time in relation to CSDH recurrence rate. 13 14 These above-mentioned steps have resulted in the current Danish CSDH treatment algorithm recommending evacuation of symptomatic CSDH by a single 13 mm burr hole above the maximum width of the haematoma followed by 37°C subdural Ringer saline irrigation and subsequent placement of a subdural drain for 24 hours. 12 , 14 The subdural drain placement has, however, been much debated as subdural drain placement may result in direct brain lesions, bleeding, seizures and intracranial infections. 15 Therefore, burr hole craniostomy with subperiosteal drainage (also known as subgaleal drainage) has been suggested as a safer and equally effective treatment of CSDH due to less invasiveness and lower risk of drain inflicted brain parenchyma injury. 15 , 19 Neurosurgeons have generally been reluctant to use active (vacuum) drainage on subdural drains due to the proximity to the brain, whereas active drainage is more common with subperiosteal drainage. 20 21 Although a direct comparison is lacking, it has been shown in a study by Sjåvik et al comparing three different Scandinavian centres using active subperiosteal drainage, passive subdural drainage and subdural drainage with continuous irrigation, that patients receiving passive drainage had the highest recurrence rate (20% vs 11%) with similar non-significant complication (8.1% vs 7.3%) and mortality rates (7.3% vs 5.8%) compared with active subperiosteal drainage. 20 Similarly, a post hoc analysis of the cSDH-Drain 15 and the TOSCAN 22 studies revealed a higher recurrence rate (23.1% vs 14.1%) in patients receiving passive compared with active drainage. 21 Accordingly, as active subperiosteal drainage might be safer 15 , 19 and more efficient, 20 21 we find it justified to examine if 24 hours active subperiosteal drainage is non-inferior to our current gold standard of 24-hour passive subdural drainage in a randomised clinical trial—the SUPERDURA trial. 12 , 14 The results obtained from the SUPERDURA trial will not only have major relevance for our neurosurgical practice but also be of international relevance as we perform the first direct comparison between two commonly used drainage methods on a national level. Methods The SUPERDURA trial is an investigator-initiated multicentre, randomised non-inferiority clinical trial involving all four neurosurgical centres in Denmark (Aalborg, Aarhus, Odense and Copenhagen). The objective is to investigate whether 24-hour active subperiosteal drainage is non-inferior to 24-hour passive subdural drainage after a single burr hole evacuation of symptomatic CSDH. Since passive subdural drainage is current treatment standard in Denmark, it is here defined as the control intervention, while active subperiosteal drainage is defined as the experimental intervention. Eligibility All patients admitted to a Danish neurosurgical department due to symptomatic CSDH confirmed on brain CT or MRI will be eligible for inclusion if they fulfil all the inclusion criteria and none of the exclusion criteria. Inclusion criteria Adult patients (≥18 years). Symptomatic CSDH confirmed on recent, for example, less than 10-day old brain CT or MRI. Admitted to a Danish neurosurgical department for surgical treatment. Patients undergoing a single burr-hole evacuation (bilateral CSDH treated with single burr-hole on both sides). Informed written and oral consent obtained prior to surgery. Exclusion criteria Patients who are mentally incapacitated (eg, not able to provide written and oral consent). Patients with known changes or abnormalities in their normal cerebrospinal fluid dynamics, for example, obstructive hydrocephalus, normal pressure hydrocephalus, intracranial hypotension and ventricular peritoneal shunt. Patients with recurrent CSDH or with previous craniotomy or other transcranial surgery within the last 5 years (for any reason). Screening and recruitment The annual number of patients receiving surgery for CSDH in Denmark is approximately 400–500 and steadily rising. 1 All Danish patients considered relevant for surgery are referred to the four participating departments. It is estimated that more than 80% of these will fulfil all the inclusion criteria and none of the exclusion criteria. 13 14 All adult patients admitted to a Danish neurosurgical department with symptomatic CSDH confirmed on recent, for example, less than 10-day old brain CT or MRI will be screened. Patient screening will be performed on admission (to determine eligibility for study participation) by the local DACHSUS representative and/or the on-call neurosurgical team. All patients screened will be listed in a screening log to evaluate the external validation of the trial and for a post-trial analysis of potential differences in the demography, clinical condition and outcome of included versus excluded patients. Informed consent procedures Informed consent will be obtained by a member of the research team on admission. Candidates will receive oral and written information about the trial before consent and randomisation. The patients will be made aware of the right to a reflection period and that they can withdraw their consent at any stage. Those not included will receive postoperative passive subdural drainage for a period of 24 hours, which is the current standard treatment in Denmark. 12 Intervention All eligible patients will be randomised preoperatively in a 1:1 ratio to either subdural or subperiosteal drain placement. Surgery is then commenced with a straight skin incision and placement of a single 13 mm burr hole above the maximum width of the haematoma 12 with use of a perforator. The dura mater and outer haematoma membrane will be opened with a cruciate incision and coagulated with bipolar diathermy. A syringe will be used to wash out the subdural collection with 37°C isotonic saline solution. When the haematoma evacuation is complete, a multichannel 3.2 mm soft silicone drain (Spiral Drain, Redax) will be inserted through the burr hole into the subdural cavity (control group—as shown in figure 1 ) 13 14 or an FG10 drain incorporated in a closed suction system (Exudrain) will be placed subperiosteally above the burr hole (experimental group—as shown in figure 2 ) depending on randomisation. Figure 1. Drain placement technique for subdural drainage. 12 (a and b) The drain is ‘doubled up’ with an anatomy forceps and introduced in the burr hole. (c) The grip is released and the drain will unfold on the surface of the inner haematoma membrane/brain. (d) The drain tip can be advanced a few centimetres without penetration of internal haematoma capsule or brain. Open in a new tab Figure 2. Drain placement technique for subperiosteal drainage. Subperiosteal drain insertion and anchorage after evacuation of chronic subdural haematoma via a single burr hole. (a) Insert the proximal end of the drain through the skin incision. (b) Puncture the scalp from below using the drain trocar at the drain exit mark. Pull on the proximal end of the drain until the most proximal fenestrae align with the border of the burr hole. Cut the distal fenestrated end of the drain, so the distal tip is just further than the end of the skin incision. (c) Insert the 2–0 Vicryl suture through the skin just further than the end of the skin incision down to the subperiosteal space, and through the distal hole of the drain and the most distal fenestra. (d) Continue the suture from the subperiosteal space through the skin from below. Gently pull on the proximal end of the drain so the drain is tight and located straight across the burr hole. Anchor the proximal end of the drain to the skin at the proximal drain exit using a simple interrupted 2–0 Vicryl suture. Close the skin incision. Open in a new tab Participants with bilateral haematomas will be registered as one case and treated similarly (single burr hole, same drainage method) on both sides. Control group: For passive subdural drains, a multichannel soft silicone drain (Spiral Drain, Redax) will be used. The direction and subdural position of the drain tip will be determined at the surgeon’s discretion and depend on the subdural space conditions. 12 The proximal part of the drain will be tunnelled 3–5 centimetres away from the scalp incision and fixed to the exit site with a proximal drain suture. The skin is closed in two layers and the proximal drain tube is connected to a soft collection bag to be fixed by a special adhesive bandage above the collar bone. 12 Experimental group: For active subperiosteal drainage, the distal part of the drain (Exudrain) will be placed subperiosteal across the burr hole and anchored by a distal drain suture. The proximal drain part will be tunnelled 3–5 centimetres away from the scalp incision and fixed to the exit site with a proximal drain suture. The skin is closed in two layers and the proximal drain tube connected to a soft collection bag with vacuum box device and fixed by a special adhesive bandage above the collar bone. 12 Vacuum (75 mm Hg) will then be applied to the drain by manual compression of the vacuum box. Both groups will subsequently be returned to the ward and allowed to mobilise immediately postoperatively, with the drains open. Routine checks will be performed every 8 hours until drain removal, to ensure that vacuum is present on subperiosteal drains and to note the drain output for both types of drain. Both drains will be removed 24 hours postoperatively, and the exact time of drain removal will be registered. In both groups, the national protocol for pausing of anti-thrombotic therapy (ATT) is followed. 23 Resumption of ATT depends on the ATT indication and medication type, but will generally, according to DACSUHS consensus, 13 14 take place 7–14 days after surgery. Medical treatment, either as an adjunct or stand-alone treatment of conservatively or surgically treated CSDH, is not used as part of standard practice in Denmark. 12 , 14 Surgery in local anaesthesia, sometimes with light intravenous sedation, will be preferred; general anaesthesia will be used primarily owing to lack of cooperation. Antibiotic prophylaxis is provided per operatively, but not regularly in the postoperative phase. According to DASCHUS guidelines 9 and Choose Wisely paradigms, postoperative CT scanning will only be used to evaluate patients with no treatment effect or clinical worsening. Randomisation and blinding Randomisation is performed using the Research Electronic Data Capture (REDCap) randomisation module. The allocation sequence will be concealed from the investigators, employing blinded block sizes and stratification by site and bilateral CSDH. The randomisation will be performed at the latest possible time before drain placement. Blinding the treating personnel is unfeasible due to the visible difference in collection bags with or without vacuum. However, the patients and the two study statisticians will be blinded to the allocation. Furthermore, statistical analyses and initial interpretation of the results will be performed using data with blinded treatment allocation. Outcomes Primary outcome The primary outcome measure is a composite outcome of 90-day mortality and recurrent symptomatic CSDH requiring ipsilateral or bilateral reoperation within 90 days. For both unilateral and bilateral haematomas, recurrence will be considered as one reoperation. Secondary outcomes Functional outcome at 90 days measured using simplified modified Rankin score questionnaire (smRSq) obtained through telephone interview between day 80 and 100. The smRSq will be dichotomised and analysed with 0–2 as favourable clinical outcome and 3–6 as unfavourable outcome. 24 Serious adverse events (SAE) necessitating new hospitalisation in the 90 days postoperative period. Complications occurring during and after surgery (intracerebral haemorrhage due to misplaced drains, acute subdural haematoma, tension pneumocephalus, wound infection, drain seepage, subperiosteal haematoma and seizures). Postoperative adverse events during the admission (thromboembolic events, infections). Length of hospitalisation. Exploratory outcomes Simplified mRSq as an ordinal outcome. Each of the components of the primary outcome. Discharge destination (home, nursing home, rehabilitation facility or other hospital department). Subgroup analyses will be performed on the primary outcome with the following subgroups: use of antithrombotics (its preoperative time of cessation, and its postoperative time of restart); time to surgery (split between median time of population); and unilateral versus bilateral CSDH. Additionally, we will analyse the recurrence rate per haematoma side. Data collection Data will be collected at enrolment, during the admission at the neurosurgery department, at discharge and at the 90-day follow-up ( table 1 , figure 3 ). Data will be obtained from hospital records, the participants and/or relatives, and will be entered into a web-based electronic case report form (eCRF) by the site investigator. Perioperative complications, drain type, drain production and exact drainage duration will be recorded at the time of drain removal by the assigned nurse and registered in REDCap by a member of the DACSUHS research team. The modified Rankin score (mRS) will be obtained at enrolment and at discharge by a member of the DACSUHS research team. An smRSq will be obtained per telephone 90 (80–100) days after surgery by a member of the DACSUHS team. Recurrence, death, time of discharge, discharge destination, complications and SAEs necessitating new hospitalisation will be recorded after the 90-day period and registered in REDCap by a member of the DACSUHS research team. Table 1. Participant timeline depicting major study events. Study period Enrolment Surgery Post-surgery Time point Admission Intraoperative Drain removal after 24 hours Discharge from neurosurgical ward 90 days follow-up Enrolment: Eligibility screen X Informed consent X Randomisation X Interventions: Placement of active SPD or passive SDD X Assessments: GCS X X mRS X X Clinical examination X X smRSq X SAE X Open in a new tab GCS, Glascow coma scale; mRS, modified Rankin score; SAE, serious adverse event; SDD, subdural drainage; smRSq, simplified modified Rankin score questionnaire; SPD, subperiosteal drainage. Figure 3. Schematic illustration of the participant timeline with major milestones. GCS, Glascow coma scale;mRS, modified Rankin score; SDD, subdural drainage; smRSq, simplified modified Rankin score questionnaire; SPD, subperiosteal drainage. Open in a new tab Data management All adult patients admitted to the neurosurgical departments with a symptomatic CSDH will be registered in the screening log in REDCap, which is a worldwide online system developed specifically for non-commercial clinical research. REDCap is administered by the Open Patient data Explorative Network at Odense University Hospital, Odense, Denmark. The data entered will be stored on secure servers in the Region of Southern Denmark. Variables will be collected directly into the case file by site investigators. Data are entered via an encrypted connection, are anonymised and fulfil the demands for data protection. All data entries and changes will be logged in REDCap and will meet the Good Clinical Practice (GCP) requirements for the use of eCRF in medical trials. The members of the research team will be responsible for all data entry. Baseline data obtained from the medical record will be registered at admission. After patient consent is obtained, online randomisation will be performed in REDCap. The database will be updated when the patient is discharged and at 90-day follow-up when the smRSq is completed. To promote data quality, eCRFs will have several built-in mechanisms to prevent data entry errors such as range checks for data values. The generated database will be monitored on a weekly basis by the principal DACSUHS investigators (JHT, RM and CB) to secure proper data filing and subsequent patient follow-up. Sample size Based on a presumed 90-day mortality of 2% and a 90-day recurrence rate of 14% in the control group (24-hour passive subdural drainage) 13 the rate of the composite outcome is 16%. We expect a relative risk reduction of recurrent CSDH and mortality of 30% for the cohort receiving active subperiosteal drainage corresponding to a composite outcome of 11.2%. The non-inferiority threshold is set at 7% increased risk, that is, if the upper confidence limit for the absolute risk difference is above 0% but below 7% active subperiosteal drainage would be classified as non-inferior. Using statistical simulations with 1000 iterations for every even sample size between 100 and 1500, we would need to include 354 participants (177 in each group) to achieve a stable power above 80% with an alpha of 5%. A sample size of 354 corresponds to a power to detect superiority of 26%. Statistical methods Dichotomous outcomes will be presented as number and percentage and analysed using mixed effect logistic regression with site as a random effect and stratification variable as fixed effects. Results will be presented as relative risks and with 95% CIs calculated by bootstrapping, G-computation or an equivalent method. Continuous outcomes will be presented as mean and 95% CIs and analysed using mixed effect linear regression with site as a random effect and stratification variables as fixed effects. Results will be presented as mean difference and 95% CIs. Count outcomes will be presented using median and IQR and analysed using van Elteren test (or a corresponding test in R) a non-parametric test able to stratify by site. Results will be presented as Hodges-Lehmann median difference and 95% CIs. Analyses will be carried out by two study statisticians blinded to the intervention (groups randomly assigned A and B) and two abstracts will be written and approved by the steering committee based on the blinded analyses. After approval of the blinded abstract, data will be unblinded. Missing data will be handled according to Jakobsen et al . 25 A detailed statistical analysis plan will be submitted before study initiation. 26 Sensitivity and subgroup analyses The primary composite outcome will be analysed per-protocol as a sensitivity analysis to the intention-to-treat principle. Subgroup analyses will be performed on the primary outcome with the following subgroups: Antithrombotic use versus no antithrombotic use. Time to surgery (split between median time of population). Unilateral versus bilateral CSDH. Recurrence of CSDH within 90 days with patients stratified on antithrombotic resumption within 7 days postoperative or after 7 days. Recurrence of CSDH within 90 days per treated haematoma side. Trial termination and stopping rules (interim analyses) Interim analyses for safety and efficacy/futility will be performed after the inclusion of 120 and 240 patients, respectively. The safety analyses will examine the occurrence of SAEs in the two groups. SAEs will be defined according to the Common Terminology Criteria for Adverse Events V.6.0. Causality will be assessed by the coordinating and principal investigators at the relevant site and reviewed and validated by the data safety monitoring committee. If the risk of SAEs is significantly different between groups (χ 2 test, alpha ≤0.05), the trial will be terminated for safety. The interim analyses of clinical efficacy/futility will be based on the primary outcome. The study will be terminated if the clinical non-inferiority threshold is reached (mixed logistic regression model with stratification variables as fixed effect and site as random effects, alpha will be adjusted based on Lan-DeMets O’Brien-Fleming approximation). At each interim analysis, an adjusted sample size will be simulated based on the current proportions. The trial will be stopped for futility if the revised sample size, conditioned on the observed primary outcomes, exceeds a total of 700 patients. Study start and end dates The study is initiated on 1 September 2025. The inclusion of 354 habile patients with CSDH is expected to last 2 years. Thus, the last inclusion is expected to occur in August 2027, meaning that the final 90-day data collection will then take place in November 2027. Final data analysis and study reporting are expected to take 6 months and the primary study results should therefore be generally accessible around May 2028. Discussion In 2018, the treatment of CSDH in Denmark was standardised based on the best available evidence. 7 , 14 The current treatment algorithm recommends 24-hour passive subdural drainage based on a retrospective Danish prediction study showing that compared with no drain placement, the subdistribution HR (SHR) of subdural drain placement was 0.3 while the SHR of subperiosteal drainage was 0.6. 8 Whether the subperiosteal drains were active or passive was not indicated, 8 but we resume based on personal experience that most were passive. However, new international studies indicate that active subperiosteal drainage may have less recurrences 20 21 and avoid the risk of drain-inflicted damage to the brain. 15 , 19 The proposed study will, accordingly, in a Danish setting, examine whether 24-hour active subperiosteal drainage is non-inferior to 24-hour passive subdural drainage after single burr hole evacuation of CSDH. We intuitively expect the subperiosteal drain method to be safer; 15 , 19 however, previously Danish data have shown less recurrences with the subdural method. 8 We find, therefore, the proposed study scientifically and ethically sound, as we currently do not know which drainage method to be superior, and previous research 15 , 21 indicates pros and cons for each technique. As we expect the subperiosteal technique to be safer, 15 , 19 the proposed study is designed as a non-inferior trial so that we, in the case of a non-significant result in our primary endpoint, can change our treatment CSDH algorithm to 24-hour active subperiosteal drainage. The study strength is that it encompasses all mentally capable CSDH patients in Denmark and the obtained results should therefore be widely generalisable to other neurosurgical facilities using a similar treatment algorithm. Another strength is the Danish social security system enabling gratuitous treatment (free access) and a social security number that allows us to keep track of our patients after hospital discharge. We expect, therefore, to include most of the available patients with CSDH and that loss to follow-up will be low. We likewise expect the number of potential cross-overs to be very low, as the only possible way to cross over in our study is if a patient randomised to subdural drainage during the haematoma evacuation procedure has so much brain expansion that the allocated subdural drain cannot be placed in the resulting subdural space. As most patients with CSDH have some degree of brain atrophy, this is most rarely experienced (we estimate one to two cases a year), and in such a case, the patient will receive a subperiosteal drain and be excluded from further analysis. Due to the randomisation, we expect a similar number of bilateral haematomas in the two study groups. Likewise, we perform stratification to separate unilateral from bilateral CSDH cases. However, counting bilateral haematomas as a single entity might artificially inflate recurrence rates in contrast to counting each haematoma side separately. One should take this into consideration when comparing our study recurrence rate with existing studies counting recurrence per haematoma side. To aid this comparison, we will also register and perform subgroup analysis on treated haematoma sides. Postoperative imaging in patients with chronic subdural haematomas is not performed routinely in Denmark as part of the national guidelines for treating patients with CSDH. 9 A routine 24-hour postoperative CT scan before final drain removal could validate final drain location and minor complications in asymptomatic patients. However, being abandoned from Danish clinical practice and because we want to evaluate the clinical impact of the randomised treatment procedures and not their resulting 24-hour postoperative imaging scan, we will continue to adhere to our established guidelines. We did not receive ethical permission to include mentally incapacitated patients, a group previously shown to encompass around 15% of the Danish CSDH cohort. 14 We acknowledge that mental capacity is not decisive for the comparison of drain location, but leaving mentally incapacitated patients out will, in our view, weaken the overall generalisability of our study, as we expect these patients to be more inflicted by their CSDH and thus could represent a more vulnerable subgroup of the CSDH cohort. Another limitation is the inability to blind the treating surgeons and nurses as the drains need to be placed in two different anatomical locations and the need for handling of the active subperiosteal drain. However, the statistical data analysis and interim analyses will be carried out by blinded assessors outside the DACSUHS consortium, which should minimise the resulting bias. Ethics and dissemination Research ethics approval The SUPERDURA protocol V.1.0, informed consent forms and all other relevant trial documents have been approved on the 13 May 2024 and 13 December 2024 by The North Denmark Region Committee on Health Research Ethics with number N-202400009. This study involves human participants. Trial conduct The trial protocol is written in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guideline. We will ensure the trial conduct follows the letter of the Declaration of Helsinki, the conditions and principles of GCP, the protocol and applicable local regulatory requirements and laws. Data Safety Monitoring Committee The Data Safety Monitoring Committee (DSMC) will consist of two active Scandinavian CSDH researchers working outside Denmark who are both independent from sponsor and with no known competing interests. Furthermore, one protocol biostatistician will be included in the DSMC. The protocol statistician will ensure that planned data review materials are delivered to the DSMC, facilitating the closed session discussion, distributing restricted-access video conference information before each meeting, producing DSMC ad hoc requests as needed and the open and closed session meeting minutes. The protocol statistician is not a committee member and does not vote but will be the main point of contact concerning data and analysis-related materials. The DSMC and the protocol statistician have unblinding privileges and are granted unlimited access to the study data. Thus, the initial responsibility of the DSMC will be to review the safety data package at planned intervals during the trial. The overall DSMC responsibilities are to: Make recommendations on further study conduct. Continuation, termination or other modifications of the study should be based on observed beneficial or adverse effects of any treatment(s) under study or low probability of achieving study objectives. Consider essential parts of the study (eg, protocol adherence, subject withdrawals, protocol violation/deviations) that might be early indicators that may impact safety. Make recommendations about study conduct, enrolment and sample size and/or data collection. Perform a risk assessment to weigh possible safety disadvantages. Evaluate the Safety Management Plan and protocol in advance of the start of the studies and during the study. Make recommendations as to whether the trial will continue as initially designed, be modified or be terminated. Data access and dissemination A written request to gain access to the data sets obtained during this study can be sent to the corresponding author, which will be discussed in the DACSHUS research team. If approved, the corresponding author will be responsible for providing access to research data requested by third parties, unless access to the data is restricted by a legal obligation (eg, non-disclosure agreement), intellectual property protection, ethical approval requirements, ethical or security reasons or other legitimate reasons. All study results, whether positive or negative, will be published in international journals. Study period Recruitment is planned to start on the 1 September 2025, for example, first patient included in September 2025. The last patient is expected to be included in August 2027. The last endpoint collection is expected in November 2027. Protocol and amendments The protocol version outlined in this material is V.1.9. Should there be a need for amendments to the study based on updates in the literature published after trial initiation or new knowledge obtained during the trial, the research team will at first address them internally and with the data monitoring committee and inform the National Committees on Health Research Ethics and BMJ through an addendum to the initial protocol. Footnotes Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Prepublication history for this paper is available online. To view these files, please visit the journal online ( https://doi.org/10.1136/bmjopen-2025-102410 ). Patient consent for publication: Consent obtained directly from patient(s). Provenance and peer review: Not commissioned; externally peer reviewed. Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. References 1. Poulsen FR, Halle B, Pottegård A, et al. Subdural hematoma cases identified through a Danish patient register: diagnosis validity, clinical characteristics, and preadmission antithrombotic drug use. Pharmacoepidemiol Drug Saf. 2016;25:1253–62. doi: 10.1002/pds.4058. [ DOI ] [ PubMed ] [ Google Scholar ] 2. Balser D, Farooq S, Mehmood T, et al. Actual and projected incidence rates for chronic subdural hematomas in United States Veterans Administration and civilian populations. J Neurosurg. 2015;123:1209–15. doi: 10.3171/2014.9.JNS141550. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 3. Rauhala M, Luoto TM, Huhtala H, et al. The incidence of chronic subdural hematomas from 1990 to 2015 in a defined Finnish population. J Neurosurg. 2020;132:1147–57. doi: 10.3171/2018.12.JNS183035. [ DOI ] [ PubMed ] [ Google Scholar ] 4. Gaist D, García Rodríguez LA, Hellfritzsch M, et al. Association of Antithrombotic Drug Use With Subdural Hematoma Risk. JAMA. 2017;317:836–46. doi: 10.1001/jama.2017.0639. [ DOI ] [ PubMed ] [ Google Scholar ] 5. Santarius T, Kirkpatrick PJ, Ganesan D, et al. Use of drains versus no drains after burr-hole evacuation of chronic subdural haematoma: a randomised controlled trial. Lancet. 2009;374:1067–73. doi: 10.1016/S0140-6736(09)61115-6. [ DOI ] [ PubMed ] [ Google Scholar ] 6. Kolias AG, Chari A, Santarius T, et al. Chronic subdural haematoma: modern management and emerging therapies. Nat Rev Neurol. 2014;10:570–8. doi: 10.1038/nrneurol.2014.163. [ DOI ] [ PubMed ] [ Google Scholar ] 7. Andersen-Ranberg NC, Poulsen FR, Bergholt B, et al. Bilateral chronic subdural hematoma: unilateral or bilateral drainage? J Neurosurg. 2017;126:1905–11. doi: 10.3171/2016.4.JNS152642. [ DOI ] [ PubMed ] [ Google Scholar ] 8. Andersen-Ranberg NC, Debrabant B, Poulsen FR, et al. The Danish chronic subdural hematoma study-predicting recurrence of chronic subdural hematoma. Acta Neurochir (Wien) 2019;161:885–94. doi: 10.1007/s00701-019-03858-9. [ DOI ] [ PubMed ] [ Google Scholar ] 9. Jensen TSR, Andersen-Ranberg N, Poulsen FR, et al. Behandling af kronisk subduralt hæmatom. Ugeskr Laeg. 2018;180 [ Google Scholar ] 10. Jensen TSR, Andersen-Ranberg N, Poulsen FR, et al. The Danish Chronic Subdural Hematoma Study-comparison of hematoma age to the radiological appearance at time of diagnosis. Acta Neurochir (Wien) 2020;162:2007–13. doi: 10.1007/s00701-020-04472-w. [ DOI ] [ PubMed ] [ Google Scholar ] 11. Hjortdal Grønhøj M, Jensen TSR, Johannsson B, et al. Early spontaneous cessation of subdural drainage after burr hole evacuation of chronic subdural hematoma and risk of recurrence. PLoS One. 2023;18:e0285750. doi: 10.1371/journal.pone.0285750. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 12. Jensen TSR, Poulsen FR, Bergholt B, et al. Drain type and technique for subdural insertion after burr hole evacuation of chronic subdural hematoma. Acta Neurochir (Wien) 2020;162:2015–7. doi: 10.1007/s00701-020-04473-9. [ DOI ] [ PubMed ] [ Google Scholar ] 13. Jensen TSR, Haldrup M, Hjortdal Grønhøj M, et al. National randomized clinical trial on subdural drainage time after chronic subdural hematoma evacuation. J Neurosurg. 2022;137:799–806. doi: 10.3171/2021.10.JNS211608. [ DOI ] [ PubMed ] [ Google Scholar ] 14. Hjortdal Grønhøj M, Jensen TSR, Miscov R, et al. Optimal drainage time after evacuation of chronic subdural haematoma (DRAIN TIME 2): a multicentre, randomised, multiarm and multistage non-inferiority trial in Denmark. Lancet Neurol. 2024;23:787–96. doi: 10.1016/S1474-4422(24)00175-3. [ DOI ] [ PubMed ] [ Google Scholar ] 15. Soleman J, Lutz K, Schaedelin S, et al. Subperiosteal vs Subdural Drain After Burr-Hole Drainage of Chronic Subdural Hematoma: A Randomized Clinical Trial (cSDH-Drain-Trial) Neurosurgery. 2019;85:E825–34. doi: 10.1093/neuros/nyz095. [ DOI ] [ PubMed ] [ Google Scholar ] 16. Ding H, Liu S, Quan X, et al. Subperiosteal versus Subdural Drain After Burr Hole Drainage for Chronic Subdural Hematomas: A Systematic Review and Meta-Analysis. World Neurosurg. 2020;136:90–100. doi: 10.1016/j.wneu.2019.12.180. [ DOI ] [ PubMed ] [ Google Scholar ] 17. Greuter L, Hejrati N, Soleman J. Type of Drain in Chronic Subdural Hematoma-A Systematic Review and Meta-Analysis. Front Neurol. 2020;11:312. doi: 10.3389/fneur.2020.00312. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 18. Pranata R, Deka H, July J. Subperiosteal versus subdural drainage after burr hole evacuation of chronic subdural hematoma: systematic review and meta-analysis. Acta Neurochir (Wien) 2020;162:489–98. doi: 10.1007/s00701-019-04208-5. [ DOI ] [ PubMed ] [ Google Scholar ] 19. Xie Y, Lu Q, Lenahan C, et al. A Comparison of Subperiosteal or Subgaleal Drainage with Subdural Drainage on the Outcomes of Chronic Subdural Hematoma: A Meta-Analysis. World Neurosurg. 2020;135:e723–30. doi: 10.1016/j.wneu.2019.12.116. [ DOI ] [ PubMed ] [ Google Scholar ] 20. Sjåvik K, Bartek J, Sagberg LM, et al. Assessment of drainage techniques for evacuation of chronic subdural hematoma: a consecutive population-based comparative cohort study. J Neurosurg. 2020;133:1113–9. doi: 10.3171/2016.12.JNS161713. [ DOI ] [ PubMed ] [ Google Scholar ] 21. Ebel F, Greuter L, Lutz K, et al. The Role of Active or Passive Drainage after Evacuation of Chronic Subdural Hematoma: An Analysis of Two Randomized Controlled Trials (cSDH-Drain-Trial and TOSCAN Trial) Diagnostics (Basel) 2022;12:3045. doi: 10.3390/diagnostics12123045. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 22. Schucht P, Fischer U, Fung C, et al. Follow-up Computed Tomography after Evacuation of Chronic Subdural Hematoma. N Engl J Med. 2019;380:1186–7. doi: 10.1056/NEJMc1812507. [ DOI ] [ PubMed ] [ Google Scholar ] 23. Nielsen J, Husted S, Münster A. Perioperativ regulering af antitrombotisk behandling - DSTH.DK. 2023. https://www.dsth.dk/pdf/PRAB_2016_WEB.pdf Available. 24. Bruno A, Akinwuntan AE, Lin C, et al. Simplified modified rankin scale questionnaire: reproducibility over the telephone and validation with quality of life. Stroke. 2011;42:2276–9. doi: 10.1161/STROKEAHA.111.613273. [ DOI ] [ PubMed ] [ Google Scholar ] 25. Jakobsen JC, Gluud C, Wetterslev J, et al. When and how should multiple imputation be used for handling missing data in randomised clinical trials - a practical guide with flowcharts. BMC Med Res Methodol. 2017;17:162. doi: 10.1186/s12874-017-0442-1. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 26. Terkelsen JH, Miscov R, Jensen TSR, et al. Active subperiosteal vs. passive subdural 24-h drainage following single burr hole evacuation of chronic subdural hematoma: statistical analysis plan for the multicenter, randomized, non-inferiority clinical trial SUPERDURA. Trials. 2026;27:129. doi: 10.1186/s13063-026-09434-8. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] BMJ Open. 2026 Apr 15. Review Process File Copyright and License information PMC Copyright notice bmjopen-2025-102410.reviewer_comments.pdf (199.5KB, pdf) Open in a new tab Articles from BMJ Open are provided here courtesy of BMJ Publishing Group ACTIONS View on publisher site PDF (573.6 KB) Cite Collections Permalink PERMALINK Copy RESOURCES Similar articles Cited by other articles Links to NCBI Databases Cite Copy Download .nbib .nbib Format: AMA APA MLA NLM Add to Collections Create a new collection Add to an existing collection Name your collection * Choose a collection Unable to load your collection due to an error Please try again Add Cancel Follow NCBI NCBI on X (formerly known as Twitter) NCBI on Facebook NCBI on LinkedIn NCBI on GitHub NCBI RSS feed Connect with NLM NLM on X (formerly known as Twitter) NLM on Facebook NLM on YouTube National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894 Web Policies FOIA HHS Vulnerability Disclosure Help Accessibility Careers NLM NIH HHS USA.gov Back to Top