Blood Clot Treatments for Stroke

(MOST Trial)

Recruiting at 70 trial locations

Overseen By Andrew Barreto, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Washington University School of Medicine

Must be taking: Thrombolytics

Must not be taking: Anticoagulants, Glycoprotein IIb/IIIa inhibitors

Disqualifiers: Pregnancy, Recent stroke, Hypertension, others

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: 1

Duration: 12 hours

514 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to determine if the drugs argatroban (an anticoagulant) or eptifibatide (a platelet aggregation inhibitor) can improve recovery after an acute ischemic stroke, a type of stroke caused by a blood clot in the brain. Researchers are comparing these treatments to a placebo to identify which works best alongside standard clot-busting medications. Individuals who have recently experienced an ischemic stroke, received clot-dissolving drugs within three hours of symptom onset, and can begin the trial drug within 75 minutes of the initial treatment may be suitable candidates. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to groundbreaking stroke recovery research.

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

Research has shown that argatroban is generally well-tolerated by patients with acute ischemic stroke. Studies have found that it can improve brain function without increasing the risk of bleeding. In one study, about 80.5% of patients treated with argatroban experienced a good recovery after 90 days. Additionally, the occurrence of unexpected problems was low, indicating that argatroban is safe for these patients.

For eptifibatide, research suggests it may be safe for patients with acute ischemic stroke, although some studies report a higher risk of bleeding. Specifically, there is an increased risk of certain types of bleeding during specific procedures. However, overall, it shows potential for successful treatment. These findings are important to consider when evaluating treatment options. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Argatroban and Eptifibatide for treating strokes caused by blood clots because they offer new approaches compared to standard treatments like tissue plasminogen activator (tPA). Argatroban works as a direct thrombin inhibitor, which helps prevent clot growth, offering an alternative for patients who might not be eligible for tPA. Eptifibatide, on the other hand, is a platelet aggregation inhibitor, which prevents platelets from clumping together and forming new clots. These distinct mechanisms of action could potentially offer more options and improve outcomes for stroke patients, making them promising additions to the current treatment landscape.

What evidence suggests that this trial's treatments could be effective for stroke?

In this trial, participants will receive either Argatroban or Eptifibatide, with some receiving a placebo. Research has shown that Argatroban, a medication that prevents blood clots, holds promise for treating sudden strokes caused by blocked blood flow (acute ischemic stroke). One study found that 80.5% of patients who received Argatroban had a good recovery after 90 days, compared to 73.3% of those who did not receive it. Argatroban has also improved brain function and is considered safer than some other treatments, such as heparin.

For Eptifibatide, research results are mixed. While it can aid in stroke recovery and is safe to use, one study found it did not reduce disability after a stroke and was linked to higher death rates. However, using it with other treatments, like rt-PA, has been safe for stroke patients if administered within a critical time period. ^{3 6 7 8 9}

Who Is on the Research Team?

Opeolu Adeoye, MD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults over 18 with acute ischemic stroke who've received IV thrombolysis within 3 hours of symptom onset. They must have an NIHSS score ≥ 6 and be able to get the study drug within 60-75 minutes after starting thrombolysis. Exclusions include recent surgery, uncontrolled high blood pressure, severe kidney issues, certain medication use, other clinical trials participation, known allergies to the drugs tested, pregnancy, previous strokes or brain injuries.

Inclusion Criteria

I received clot-busting medication within 3 hours after my stroke started.

I can take the study medication within 60 to 75 minutes after starting IV thrombolysis.

You have a score of 6 or higher on the NIH Stroke Scale before receiving IV thrombolytic treatment.

Exclusion Criteria

Informed consent from the patient or the legally authorized representative was not or could not be obtained

Women who could become pregnant have a positive pregnancy test in their urine or blood.

I have taken blood thinners like Fondaparinux, apixaban, or rivaroxaban in the last 2 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive argatroban or eptifibatide or placebo in addition to standard thrombolysis treatment

12 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

What Are the Treatments Tested in This Trial?

Interventions

• Argatroban
• Eptifibatide
• Placebo

Trial Overview The MOST trial is testing whether argatroban or eptifibatide improves recovery at 90 days compared to a placebo in patients receiving standard clot-dissolving treatments for stroke. The study also allows additional mechanical clot removal as part of usual care.

How Is the Trial Designed?

Group I: Eptifibatide Experimental Treatment 1 Intervention

135µg/kg bolus followed by 0.75µg/kg/min infusion for two hours

Group II: Argatroban Experimental Treatment 1 Intervention

100µg/kg bolus followed by 3µg/kg per minute for 12 hours

Group III: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10775075/

Argatroban in Patients With Acute Ischemic Stroke With Early ... The number of patients with good functional outcome at 90 days was 240 (80.5%) in the argatroban group and 222 (73.3%) in the control group ( ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2324242625000737

Efficacy and Safety of Argatroban in Acute Branch ... Studies of argatroban in stroke have suggested that it can yield better clinical outcomes. However, there is currently a lack of clinical ...

3. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1364895/full

Efficacy and safety of Argatroban in patients with acute ... The results of this study suggested that Argatroban could improve neurological deterioration in AIS patients, with a low incidence of adverse ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04275180

NCT04275180 | Efficacy Argatroban in Ischemic Stroke ... According to a study in Japan, argatroban is superior to heparin in the treatment of cardiogenic stroke and has higher safety; a meta-analysis involving 14 ...

5. neurology.org neurology.org/doi/10.1212/WNL.0000000000211993

Adjunctive Argatroban Therapy in Patients with Acute ... Argatroban, a direct thrombin inhibitor, has emerged as a novel treatment for AIS in recent trials and shows improved neurological outcomes.

6. sciencedirect.com sciencedirect.com/science/article/pii/S1052305724005949

Safety and efficacy of argatroban combined with ... Our study suggested that argatroban can improve neurological outcomes for mild to moderate LAA patients but not increase the risk of bleeding.

7. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/2813359

Argatroban in Patients With Acute Ischemic Stroke ... The number of patients with good functional outcome at 90 days was 240 (80.5%) in the argatroban group and 222 (73.3%) in the control group ( ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10957773/

The effect of argatroban on early neurological deterioration ... Argatroban was found to be the only anticoagulant that achieved significant positive results in the early stage of large-artery ischemic stroke ...

9. ahajournals.org ahajournals.org/doi/10.1161/strokeaha.117.016720

Randomized, Multicenter Trial of ARTSS-2 (Argatroban ... We conducted a randomized exploratory study to assess safety and the probability of a favorable outcome with adjunctive argatroban, a direct thrombin-inhibitor.