Restarting Early Versus Later Anticoagulation for Chronic Subdural Hematoma With Atrial Fibrillation (RELACS)

Restarting Early Versus Later Anticoagulation for Chronic Subdural Hematoma With Atrial Fibrillation (RELACS): An International Multicenter, Randomized Controlled, Two-arm, Assessor-blinded, Trial

The goal of this randomized clinical trial is to assess the benefit of early resumption versus late resumption of oral anticoagulation medication in adults with atrial fibrillation undergoing surgery for chronic subdural hematoma. The main questions it aims to answer are:

• Does anticoagulation resumption 5 days after surgery as compared to 30 days after surgery result in fewer thromboembolic complications, without increasing the risk for bleeding?
• Does anticoagulation resumption 5 days after surgery as compared to 30 days after surgery affect the risk of reoperation, functional outcome, mortality, and healthcare use?

Researchers will compare early anticoagulation resumption (5 days) and late anticoagulation resumption (30 days) after chronic subdural hematoma surgery.

Participants will either resume the medication 5 days or 30 days after the surgery. The participants will be followed up for 3 months after the surgery.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation (AF); Chronic Subdural Hematoma
• Intervention / Treatment: Drug: Early Resumption of Oral Anticoagulation Therapy; Drug: Late Resumption of Oral Anticoagulation Therapy

• Study Type: Interventional
• Enrollment (Estimated): 332
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rahul Raj, MD, PhD; Phone Number: +358504272516; Email: rahul.raj@hus.fi
• Study Contact Backup: Name: Jarno Satopää, MD, PhD; Phone Number: +358504286743‬; Email: jarno.satopaa@hus.fi

Study Locations

• Finland
  • Pirkanmaa
    • Tampere, Pirkanmaa, Finland, 33520
      • Not yet recruiting
      • Tampere University Hospital
      • Contact: Teemu Luoto, MD, PhD; Phone Number: ‭+35840703 9696‬; Email: teemu.luoto@pirha.fi
      • Principal Investigator: Teemu Luoto, MD, PhD
      • Sub-Investigator: Minna J Rauhala, MD, PhD
  • Pohjois-Pohjanmaa
    • Oulu, Pohjois-Pohjanmaa, Finland, 90220
      • Not yet recruiting
      • Oulu University Hospital
      • Contact: Oula Knuutinen, MD, PhD; Phone Number: ‭+358405842879‬; Email: oula.knuutinen@oulu.fi
      • Principal Investigator: Oula Knuutinen, MD, PhD
      • Sub-Investigator: Tommi Korhonen, MD, PhD
      • Sub-Investigator: Sami Tetri, MD, PhD
  • Pohjois-Savo
    • Kuopio, Pohjois-Savo, Finland, 70200
      • Not yet recruiting
      • Kuopio University Hospital
      • Contact: Nils Danner, MD, PhD; Phone Number: ‭+358400911568‬; Email: nils.danner@pshyvinvointialue.fi
      • Principal Investigator: Nils Danner, MD, PhD
      • Sub-Investigator: Ville Leinonen, MD, PhD
      • Sub-Investigator: Timo Koivisto, MD, PhD
  • Uusimaa
    • Helsinki, Uusimaa, Finland, 00260
      • Recruiting
      • Helsinki University Hospital
      • Contact: Rahul Raj, MD, PhD; Phone Number: +358504272516; Email: rahul.raj@hus.fi
      • Contact: Jarno Satopää, MD, PhD; Phone Number: +358504286743‬; Email: jarno.satopaa@hus.fi
      • Sub-Investigator: Pihla Tommiska, MD, PhD
      • Sub-Investigator: Miikka Korja, MD, PhD
      • Sub-Investigator: Riku Kivisaari, MD, PhD
      • Sub-Investigator: Teemu Luostarinen, MD, PhD
      • Sub-Investigator: Jyri J Virta, MD, PhD
      • Sub-Investigator: Simo Taimela, MD, PhD
      • Sub-Investigator: Teppo LN Järvinen, MD, PhD
      • Principal Investigator: Rahul Raj, MD, PhD
      • Principal Investigator: Jarno Satopää, MD, PhD
  • Varsinais-Suomi
    • Turku, Varsinais-Suomi, Finland, 20520
      • Not yet recruiting
      • Turku University Hospital
      • Contact: Jussi P Posti, MD, PhD; Phone Number: ‭+358443804143‬; Email: jussi.posti@tyks.fi
      • Principal Investigator: Jussi P Posti, MD, PhD
      • Sub-Investigator: Dan Laukka, MD, PhD
• Sweden
  • Region Stockholm
    • Stockholm, Region Stockholm, Sweden, 17164
      • Not yet recruiting
      • Karolinska University Hospital
      • Contact: Jiri Bartek, MD, PhD; Phone Number: +46707948670‬; Email: jiri.bartek@regionstockholm.se
      • Principal Investigator: Jiri Bartek, MD, PhD
      • Sub-Investigator: Alexander Fletcher-Sandersjöö, MD, PhD
      • Sub-Investigator: Bjartur Saemundsson, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years.
• Patients with a symptomatic unilateral or bilateral CSDH requiring burr-hole evacuation with drainage (CSDH is predominantly hypodense or isodense on imaging [CT/MRI]; clinical symptoms attributable to the CSDH; patients with bilaterally operated CSDHs will be treated with the same protocol on both sides and analyzed as a single study participant).
• Patients that are on an oral anticoagulation medication due to permanent, persistent or paroxysmal spontaneous atrial fibrillation previously known
• Randomization done within 4 days of the surgery

Exclusion Criteria:

• Intraoperative or immediate postoperative hemorrhagic complication
• CSDH requiring surgical treatment other than burr-hole evacuation (e.g. craniotomy)
• Prior CSDH surgery within 12 months
• Cerebrospinal fluid shunt
• CSDH is in an arachnoid cyst
• If the operated hematoma is revealed to be a cerebrospinal fluid collection (hygroma)
• Conditions other than atrial fibrillation that require anticoagulation, including therapeutical dose of low molecular-weight heparin or heparin (for example, pulmonary embolism, deep vein thrombosis, hypercoagulability syndromes)
• Mechanical heart valve(s)
• Moderate or severe mitral stenosis (other valvular diseases and biological valves are eligible)
• Contraindication to anticoagulation medication (for example bleeding disorder, documented high risk of fall [e.g. due to severe alcoholism], severe thrombocytopenia, severe anemia)
• Concomitant use of antiplatelet medication
• Moderate to severe renal insufficiency (creatinine clearance <30 ml/min or on dialysis)
• Not a permanent resident in Finland (for Finnish patients) or not a permanent resident in Region Stockholm (for Swedish patients)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early resumption; Oral anticoagulation therapy is resumed on the 5th postoperative day following burr-hole surgery for chronic subdural hematoma.	Drug: Early Resumption of Oral Anticoagulation Therapy; The patient's prescribed anticoagulant therapy for atrial fibrillation is resumed on the 5th postoperative day following burr-hole surgery for chronic subdural hematoma. This early resumption strategy is compared to the standard practice of resuming anticoagulation therapy on the 30th postoperative day.
Active Comparator: Late resumption; Oral anticoagulation therapy is resumed on the 30th postoperative day following burr-hole surgery for chronic subdural hematoma.	Drug: Late Resumption of Oral Anticoagulation Therapy; The patient's prescribed anticoagulant therapy for atrial fibrillation is resumed on the 30th postoperative day following burr-hole surgery for chronic subdural hematoma. This standard resumption strategy is compared to the early approach of resuming anticoagulation therapy on the 5th postoperative day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of composite outcome of vascular events	Rate of the composite outcome that combines thromboembolic events (ischemic stroke, systemic embolism), hemorrhagic events (intracranial hemorrhage, major extracranial bleeding), and vascular death.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of different components of the primary composite outcome	Separation of the components of the primary composite outcome (thromboembolic, hemorrhagic, vascular death).	90 days
Rate of patients with favorable functional outcome	Assessed using the modified Rankin Scale (mRS), which ranges from 0 (no symptoms) to 6 (death).	90 days
Rate of reoperation	Reoperation for the initially treated chronic subdural hematoma.	90 days
Rate of all-cause mortality		90 days and 12 months
Participants' healthcare use	Number and type of unscheduled emergency radiological examinations, - number of emergency department visits, postoperative total hospitalization days	90 days

Collaborators and Investigators

• Sponsor: Rahul Raj
• Collaborators: Karolinska University Hospital; Turku University Hospital; Oulu University Hospital; Kuopio University Hospital; Tampere University Hospital
• Investigators: Study Chair: Rahul Raj, MD, PhD, Helsinki University Hospital & University of Helsinki; Principal Investigator: Jarno Satopää, MD, PhD, Helsinki University Hospital & University of Helsinki; Principal Investigator: Jussi P Posti, MD, PhD, Turku University Hospital and University of Turku; Principal Investigator: Teemu Luoto, MD, PhD, Tampere University Hospital and Tampere University; Principal Investigator: Nils Danner, MD, PhD, Kuopio University Hospital and University of Eastern Finland; Principal Investigator: Oula Knuutinen, MD, PhD, Oulu University Hospital and University of Oulu; Principal Investigator: Jiri Bartek, MD, PhD, Karolinska University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: November 18, 2024
• First Submitted That Met QC Criteria: November 18, 2024
• First Posted (Actual): November 19, 2024

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 21, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: stroke; surgery; atrial fibrillation; prognosis; hemorrhage; warfarin; oral anticoagulation; chronic subdural hematoma; direct oral anticoagulants
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Pathologic Processes; Heart Diseases; Chronic Disease; Disease Attributes; Arrhythmias, Cardiac; Hemorrhage; Craniocerebral Trauma; Trauma, Nervous System; Intracranial Hemorrhages; Intracranial Hemorrhage, Traumatic; Atrial Fibrillation; Hematoma, Subdural; Hematoma, Subdural, Chronic; Hematoma
• Other Study ID Numbers: HUS/7351/2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Researcher-initiated data sharing is not possible due to the Finnish Secondary Use Act (552/2019). Thus, all requests to process data for purposes permitted by the Secondary Use Act are given based on an official decision made by FINDATA (https://findata.fi/en/).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No