Blood Clot Prevention Therapies for COVID-19
(ACTIV-4A Trial)

Recruiting in Palo Alto (17 mi)

+99 other locations

Overseen byMikhail Kosiborod, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Waitlist Available

Sponsor: Matthew Neal MD

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a randomized, open label, adaptive platform trial to compare the effectiveness of antithrombotic and additional strategies for prevention of adverse outcomes in COVID-19 positive inpatients

Eligibility Criteria

This trial is for hospitalized COVID-19 patients aged 18 or older with Type 2 diabetes, heart failure, severe illness requiring ICU care, or moderate illness with additional risk factors like oxygen needs over 2 liters per minute. Patients must be enrolled within 72 hours of hospital admission or positive COVID test and expected to stay in the hospital for more than 72 hours.

Inclusion Criteria

Criterion: Two or more of the following -

I am over 65 or have at least two of the listed health conditions.

Enrolled within 72 hours of hospital admittance or 72 hours of positive COVID test

See 10 more

Exclusion Criteria

You are expected to pass away very soon.

Pregnancy

I am currently taking an SGLT2 inhibitor medication.

See 3 more

Treatment Details

Interventions

Crizanlizumab Injection (Monoclonal Antibodies)
P2Y12 (Antiplatelet agent)
prophylactic heparin (Anticoagulant)
SGLT2 inhibitor (SGLT2 Inhibitor)
theraputic heparin (Anticoagulant)

Trial OverviewThe study compares antithrombotic strategies (like heparin) and other treatments (such as SGLT2 inhibitors and Crizanlizumab Injection) to prevent adverse outcomes in COVID-19 inpatients. It's a randomized trial where patients are assigned different treatments by chance.

Participant Groups

8Treatment groups

Experimental Treatment

Group I: Therapeutic Dose Anticoagulation + P2Y12 inhibitorExperimental Treatment2 Interventions

increased dose of heparin above standard of care with an added P2Y12 inhibitor This Arm enrolled moderate illness patients only. Enrollment of moderate illness patients in the trial was ended per DSMB on June 19, 2021 and results are published in PMID: PMID: 35040887 (JAMA, January, 2022) (see reference section for citation)

Group II: Therapeutic Dose AnticoagulationExperimental Treatment1 Intervention

increased dose of heparin above standard of care. 1.0 - This arm was stopped in severe patients in December 2020 and results are published in PMID: 34351722 (NEJM, August, 2021) (see reference section for citation). This arm was stopped for moderate patients in January 2021.

Group III: Standard of Care + SGLT2 inhibitorExperimental Treatment1 Intervention

Standard of care plus SGLT2 inhibitor This arm will enroll moderate and severe illness patients This arm was ended in March 2023

Group IV: Standard of Care + CrizanlizumabExperimental Treatment1 Intervention

Standard of care plus crizanlizumab infusion This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022.

Group V: Standard of Care (SGLT2 arm)Experimental Treatment1 Intervention

Standard of care only This arm will enroll moderate and severe illness patients This arm was ended in March 2023

Group VI: Standard of Care (Criza)Experimental Treatment1 Intervention

Standard of care only This arm will enroll moderate and severe illness patients This arm was ended for all patients per the DSMB in September 2022.

Group VII: Prophylactic Dose Anticoagulation + P2Y12 inhibitorExperimental Treatment2 Interventions

Heparin standard of care with an added P2Y12 inhibitor This Arm enrolled severe illness patients only. Enrollment of severe illness patients in the trial was ended per DSMB in June 2022.

Group VIII: Prophylactic Dose AnticoagulationExperimental Treatment1 Intervention

Heparin standard of care 1.0 - this arm was stopped for all patients in January, 2021 and results are published in PMID: 34351721 (NEJM, August, 2021) (see reference section for citation)