Timing to Restart Direct Oral Anticoagulants After Traumatic Intracranial Haemorrhage

NCT06322953 | Recruiting Phase 3 DMC

• 1 other identifier: RG442-21
• Study Type: interventional
• Target: 1,084
• Locations: 1 country
• Sites: 2

Brief Summary

Older people falling from a standing height is the most common cause of hospital admission for head injury. Up to 1 in 3 patients admitted are taking a tablet medication which thins the blood, known as an oral anticoagulant. This type of medication can increase the likelihood of bleeding in the brain. Many patients are taking oral anticoagulation due to having an irregular heartbeat (called atrial fibrillation) or because of having a previous stroke or blood clots. When a scan shows blood in the brain, oral anticoagulation is nearly always stopped. However, this leaves the question of when it is safe to restart them. The risk of making the bleeding in the brain worse must be balanced against the risk of having a stroke or blood clots. There is no clear evidence on the safest time to restart oral anticoagulation, but most neurosurgeons advise restarting them 1-4 weeks after head injury. The number of people who have a bleed on their brain after a head injury is increasing and further brain bleeding or a stroke can have a serious effect on patients' lives and their on-going healthcare needs. Public and patient groups have highlighted that many patients want to stop taking oral anticoagulation after a bleed but they may be unaware of the vital importance of restarting this medication to prevent strokes and blood clots. The most popular oral anticoagulation prescribed has changed in recent years from warfarin to newer medications called Direct Oral Anti-Coagulants (DOACs). This trial will recruit 1084 people who are admitted to hospital with a bleed on the brain caused by a head injury who were taking oral anticoagulation before their head injury and have been prescribed a Direct Oral Anti-Coagulant (DOAC) for previously diagnosed medical condition. Patients on other Oral Anti-Coagulants, such as Warfarin may also be able to take part. The main purpose of the trial is to determine when is most beneficial time for people to start or restart a DOAC after their head injury. People will be asked to start the medication either 1 week or 4 weeks after their head injury. They will be then followed closely for 12 weeks and any major bleeding events or a blood clots (thrombotic events) such as a stroke or heart attack will be recorded. The study will also look at the person's overall quality of life, how they recover physically, the number of people who die, the costs of the treatment, and the attitudes of people and their caregivers to starting or restarting a DOAC.

Conditions

Traumatic Intracranial Haemorrhage

Keywords

Direct Oral Anticoagulants; Randomised Trial

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with haemorrhagic or thrombotic event within 12 weeks following tICrH.

  The total number of patients that have a haemorrhagic or thrombotic event within 12 weeks following tICrH.

  12 weeks

Secondary Outcomes (10)

• Time to first haemorrhagic or thrombotic event.

  12 weeks

• Time to first haemorrhagic event

  12 weeks

• Time to first thrombotic event

  12 weeks

• Time to death

  12 and 26 weeks

• Functional outcome measured using modified Rankin Scale (mRS)

  12 and 26 weeks

Study Arms (2)

Start/Restart DOAC at 1 week

ACTIVE COMPARATOR

Participants will be restarted/started on DOAC 1 week post traumatic intracranial hemorrhage (tICrH).

Drug: Direct-Acting Oral Anticoagulants (used as per local standard practice)

Start/Restart DOAC at 4 weeks

ACTIVE COMPARATOR

Participants will be restarted/started on DOAC 4 weeks post traumatic intracranial hemorrhage (tICrH).

Drug: Direct-Acting Oral Anticoagulants (used as per local standard practice)

Interventions

Direct-Acting Oral Anticoagulants (used as per local standard practice) DRUG

Direct-acting oral anticoagulants to be prescribed as per local standard practice at either 1 or 4 weeks.

Also known as: Apixaban, Dabigatran Etexilate Mesilate, Edoxaban, Rivaroxaban

Start/Restart DOAC at 1 week; Start/Restart DOAC at 4 weeks

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent obtained from participant / participants' legal representative / participants' Consultee and ability to comply with the requirements of the trial
• Adult ≥18 years with traumatic intracranial haemorrhage (tICrH) in the past 1 week who were taking oral anticoagulants (OAC) prior to admission
• Oral anticoagulants include any DOAC or Vitamin K antagonist (VKA) (e.g. Warfarin), prescribed for atrial fibrillation (AF) or venous thromboembolism (VTE) prior to admission for tICrH
• At high risk for thromboembolic complications (CHA2DS2VASc ≥2 in men and ≥3 in women)

You may not qualify if:

• Patients whose traumatic intracranial haemorrhage is a chronic subdural haematoma
• Patients with mechanical heart valve
• Patients with plan to start/restart anti-platelet therapy within 12 weeks of tICrH
• Abbreviated Injury Scale other than head with a score \>3
• Pregnancy
• Participants with a hypersensitivity or contraindication to Direct Oral Anticoagulant (DOAC)
• Participant with bleeding where it would be unsafe to restart DOAC at 1 week
• Participant with clinical reason to restart DOAC before 4 weeks or complete within 12 weeks
• Concomitant p-gp and CYP3A4 inducers/inhibitors
• Indication to stay on VKA (Warfarin) rather than switching to DOAC (e.g. severe renal impairment)

Sponsors & Collaborators

• Walton Centre NHS Foundation Trust: lead
• University of Liverpool: collaborator
• National Institute for Health Research, United Kingdom: collaborator
• University Hospital Plymouth NHS Trust: collaborator

Study Sites (2)

University Hospitals Plymouth NHS Trust

Plymouth, Devon, PL6 8DH, United Kingdom

RECRUITING

The Walton Centre NHS Foundation Trust

Liverpool, Mersyside, L9 7LJ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Intracranial Hemorrhage, Traumatic

Interventions

Factor Xa Inhibitors; apixaban; Dabigatran; edoxaban; Rivaroxaban

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Anticoagulants; Hematologic Agents; Therapeutic Uses; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines

Study Officials

• Catherine McMahon

  Northern Care Alliance NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura Wright

CONTACT

+44(0)151 795 8751; restart.trial@liverpool.ac.uk

Ben Hardwick

CONTACT

+44(0)151 795 8751; restart.trial@liverpool.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomised Controlled Trial

Study Record Dates

• First Submitted: February 26, 2024
• First Posted: March 21, 2024
• Study Start: March 10, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): July 31, 2028
• Last Updated: April 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)