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Monoclonal Antibodies

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

Phase 4

Waitlist Available

Led By Mikhail Kosiborod, MD

Research Sponsored by Matthew Neal MD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

For moderate illness severity, participants are required to meet one or more of the following risk criteria: Age ≥ 65 years or ≥2 of the following - O2 supplementation > 2 liters per minute, BMI ≥ 35, GFR ≤ 60, History of Type 2 diabetes, History of heart failure (regardless of ejection fraction), D dimer ≥ 2x the site's upper limit of normal (ULN), Troponin ≥ 2x the site's ULN, BNP≥100 pg/mL or NT-proBNP≥300 pg/mL, CRP ≥50 mg/L

Severe illness severity - defined as ICU level of care at the time of randomization (receiving HFNO, NIV, IV, vasopressors or inotropes, or ECMO)

Must not have

Open label treatment with any SGLT2 inhibitor

Requirement for chronic mechanical ventilation via tracheostomy prior to hospitalization

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 90 days from enrollment

Awards & highlights

Drug Has Already Been Approved

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing different ways to prevent blood clots in people who have COVID-19.

Who is the study for?

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.

What is being tested?

The 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.

What are the potential side effects?

Potential side effects may include bleeding risks from antithrombotic agents like heparin, possible kidney issues from SGLT2 inhibitors, and reactions such as anemia or uncontrolled bleeding related to Crizanlizumab.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I am in the ICU receiving critical care treatments.

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I have a history of Type 2 diabetes.

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I need more than 2 liters of oxygen per minute.

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I have a history of heart failure.

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I am 18 years old or older.

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I am currently hospitalized due to COVID-19.

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I am hospitalized but not in the ICU or on advanced support like ventilators or ECMO.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am currently taking an SGLT2 inhibitor medication.

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I needed a machine to help me breathe through a tube in my neck before I was hospitalized.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 90 days from enrollment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~90 days from enrollment

This trial's timeline: 3 weeks for screening, Varies for treatment, and 90 days from enrollment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

21 Day Organ Support (respiratory or vasopressor) Free Days

Secondary study objectives

Acute kidney injury

Days free of death

Death Composite

+2 more

Other study objectives

Primary Safety Endpoint of Major Bleeding

Secondary Safety Endpoint of HIT

Awards & Highlights

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

6Treatment 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: 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 VI: 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)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

SGLT2 inhibitor

2019

Completed Phase 4

~17870

0 / 10Eligibility criteria met