Timing of Anticoagulation After Intracranial Hemorrhage

(Restart tICrH Trial)

Overseen By Patrick Lawrence

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Texas at Austin

Must be taking: Direct oral anticoagulants

Must not be taking: Antiplatelet therapy

Disqualifiers: Mechanical valve, Pregnancy, Renal function, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 64

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal time to restart blood thinners (anticoagulants) after a brain bleed due to injury, to reduce the risk of clots and serious bleeding. It compares restarting the medication after 1, 2, or 4 weeks. Individuals who have experienced a brain bleed while on blood thinners for conditions like atrial fibrillation (irregular heartbeat) and are at risk for strokes or clots may be suitable candidates. The goal is to identify which timing minimizes the risk of further bleeding or dangerous clots. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment decisions.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop your current medications, but it focuses on restarting anticoagulation after a brain bleed. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that restarting blood thinners after a brain bleed can be safe if timed correctly. Waiting more than 30 days to restart them has been linked to worse outcomes, such as a higher risk of new strokes and death in the hospital. However, starting them too soon can also be risky.

One study found that over 70% of patients experienced some increase in bleeding within the first 24 hours after a brain bleed. This suggests that waiting more than a day before restarting blood thinners might be safer. Another study showed that restarting blood thinners can lower the risk of death from all causes compared to not restarting them at all.

These findings suggest that restarting blood thinners after a short delay might be safer. However, the exact timing can vary, and this trial aims to find the safest option. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores the optimal timing for starting anticoagulation therapy after an intracranial hemorrhage. Unlike the standard practice, which often involves a cautious delay, this study aims to determine if starting anticoagulation after 1, 2, or 4 weeks can improve outcomes without increasing risks. By carefully examining these different timeframes, the trial hopes to find a balance that maximizes the benefits of anticoagulation while minimizing the potential for further bleeding. This could lead to more personalized and effective care for patients recovering from such injuries.

What evidence suggests that this trial's treatments could be effective for minimizing thrombotic events and major bleeding after intracranial hemorrhage?

This trial will compare the timing of restarting anticoagulation after intracranial hemorrhage. Research has shown that restarting blood thinners after brain bleeding can help prevent additional strokes, especially in individuals with conditions like atrial fibrillation. Studies have found that resuming these medications within 14 to 28 days after the bleeding can be beneficial, depending on the severity of the initial brain bleed. In this trial, participants will be randomized to initiate anticoagulation 1 week, 2 weeks, or 4 weeks following injury. Restarting blood thinners within 2 weeks has been linked to a low risk of bleeding, about 4.5%, and generally good outcomes. Observational evidence suggests that resuming treatment around 7 to 8 weeks can effectively prevent blood clots while reducing the risk of further bleeding. Therefore, timing is crucial to maximize benefits and minimize risks. ^{6 7 8 9 10}

Who Is on the Research Team?

Truman J Milling, MD

Principal Investigator

Seton Dell Medical School Stroke Institute

Are You a Good Fit for This Trial?

This trial is for patients who've had a traumatic brain bleed while on blood thinners for atrial fibrillation or clot prevention. They should be at high risk of stroke, with specific criteria met (CHA2DS2-VASc score >3), and their doctors are considering restarting anticoagulants within 1 to 4 weeks after the bleeding event.

Inclusion Criteria

I am at high risk for stroke with a CHA2DS2-VASc score over 3.

I have a recent brain bleed while on blood thinners for AF or VTE.

My doctor plans to restart my blood thinner medication after a brain bleed.

Exclusion Criteria

If you have bleeding that your doctor thinks is not safe to start or stop a specific medication after a week or four weeks.

I am not taking medication that strongly affects certain liver enzymes.

You are allergic to the drug or have a specific reason not to take it according to the label.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to restart anticoagulation at 1 week, 2 weeks, or 4 weeks following injury

4 weeks

Weekly visits for 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 days

Weekly visits for 60 days

What Are the Treatments Tested in This Trial?

Interventions

• Anticoagulants

Trial Overview The study tests when it's best to restart blood thinners (DOACs) after a brain bleed due to injury: at 1 week, 2 weeks, or 4 weeks. The goal is to balance preventing clots against the risk of more bleeding. It uses random assignment and looks at thrombotic and bleeding events over two months.

How Is the Trial Designed?

Group I: 4 weeks Experimental Treatment 1 Intervention

Time to delay the initiation of anticoagulation is determined at randomization. Patients will be randomized to initiate anticoagulation 1 week, 2 weeks, or 4 weeks following injury.

Group II: 2 weeks Experimental Treatment 1 Intervention

Time to delay the initiation of anticoagulation is determined at randomization. Patients will be randomized to initiate anticoagulation 1 week, 2 weeks, or 4 weeks following injury.

Group III: 1 week Experimental Treatment 1 Intervention

Time to delay the initiation of anticoagulation is determined at randomization. Patients will be randomized to initiate anticoagulation 1 week, 2 weeks, or 4 weeks following injury.

Who Is Running the Clinical Trial?

University of Texas at Austin

Lead Sponsor

Trials

387

Recruited

86,100+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12098311/

Oral Anticoagulation following intracranial haemorrhage in ... Oral anticoagulation (OAC) is highly effective at preventing stroke in the setting of AF, but is consistently underused.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2772374724004885

Outcomes of Reinitiating Direct Oral Anticoagulants After ... Reinitiating DOACs within 14 and 28 days after discharge most benefited patients with low and high ICH severity, respectively.

3. heartrhythmjournal.com heartrhythmjournal.com/article/S1547-5271(25)02602-5/fulltext

Effect of oral anticoagulant therapy on adverse outcomes in ... Observational evidence suggests that resuming anticoagulation 7–8 weeks after ICH may strike a favorable balance between thrombotic protection ...

4. ahajournals.org ahajournals.org/doi/10.1161/strokeaha.116.013343

Anticoagulant-Associated Intracranial Hemorrhage in the ... In patients taking oral anticoagulants (OACs), the annual rate of intracranial hemorrhage is 0.3% to 0.6%. Of these bleeds, 46% to 86% are ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06322953

Timing to Restart Direct Oral Anticoagulants After ... The bleeding rate was only 4.5% in those who restarted their OAC within 2 weeks, with a net benefit (Hazard ratio 0.384 combining thrombosis, bleeding and death ...

6. ahajournals.org ahajournals.org/doi/10.1161/JAHA.123.032094

Optimal Timing for Resumption of Anticoagulation After ... Withholding anticoagulation >30 days was associated with severe baseline ICH, higher in‐hospital case fatality, and elevated AIS risk.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10249073/

Management of oral anticoagulant therapy after intracranial ... A wide range of optimal time range from 72 h (92) to 10–30 weeks (91) has been reported. A recent retrospective study performed in Korea showed ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1538783623007900

resumption of oral anticoagulant therapy after intracranial ... The first 24 hours post-ICH are particularly high risk with >70% of patients reported to develop at least some hematoma expansion during this time [19], and ...

9. ahajournals.org ahajournals.org/doi/10.1161/01.str.26.8.1471

Oral Anticoagulants and Intracranial Hemorrhage | Stroke Anticoagulation to conventional intensities increases the risk of intracranial hemorrhage 7- to 10-fold, to an absolute rate of nearly 1%/y for many stroke- ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11934040/

Balancing Risks and Timing: Reinitiating DOACs After ... Reinitiating DOAC therapy was associated with a lower risk of all-cause mortality compared with withholding antithrombotic treatment.