Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 ACUTE

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Matthew Neal MD
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Calcium heparin; Canagliflozin; Clopidogrel; Dalteparin; Dapagliflozin; Empagliflozin; Enoxaparin; Enoxaparin sodium; Ertugliflozin; Heparin; Heparin, Low-Molecular-Weight; Sodium-Glucose Transporter 2 Inhibitors; Ticagrelor; Tinzaparin

Criteria

Inclusion Criteria:

• ≥ 18 years of age

• Hospitalized for COVID-19

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

• Expected to require hospitalization for > 72 hours

Exclusion Criteria:

• Imminent death

• Requirement for chronic mechanical ventilation via tracheostomy prior to hospitalization

• Pregnancy

Inclusion Criteria for Arm E

Inclusion criteria contained in the master protocol in addition to the following:

Moderate illness severity - defined as non-ICU level of care at the time of randomization (not receiving high flow nasal oxygen (HFNO), non-invasive ventilation (NIV), invasive ventilation (IV), vasopressors or inotropes, or extracorporeal membrane oxygenation (ECMO) OR Severe illness severity - defined as ICU level of care at the time of randomization (receiving HFNO, NIV, IV, vasopressors or inotropes, or ECMO)

For moderate illness severity, participants are required to meet one or more of the following risk criteria:

1. Age ≥ 65 years or

2. ≥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

Exclusion Criteria for Arm E

• Exclusion criteria contained in the master protocol, and

• Any condition that, in the opinion of the investigator, precludes the use of crizanlizumab such as uncontrolled bleeding or severe anemia (hemoglobin<4 g/dL)

• Open label treatment with crizanlizumab within the past three months

Inclusion Criteria for Arm F

Inclusion criteria contained in the master protocol in addition to the following:

Moderate illness severity - defined as non-ICU level of care at the time of randomization (not receiving high flow nasal oxygen (HFNO), non-invasive ventilation (NIV), invasive ventilation (IV), vasopressors or inotropes, or extracorporeal membrane oxygenation (ECMO)) OR Severe illness severity - defined as ICU level of care at the time of randomization (receiving HFNO, NIV, IV, vasopressors or inotropes, or ECMO)

For moderate illness severity, participants are required to meet one or more of the following risk criteria:

1. Age ≥ 65 years or

2. ≥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

Exclusion Criteria for Arm F

In addition to the exclusion criteria noted in the master protocol, arm-specific exclusion criteria are as follows:

• Known hypersensitivity to any SGLT2 inhibitors

• Type 1 diabetes

• History of diabetic ketoacidosis

• eGFR <20 and/or requirement for renal replacement therapy

• Open label treatment with any SGLT2 inhibitor

• Based on a recommendation from the ACTIV4 DSMB on December 19, 2020, enrollment of patients requiring ICU level of care into the therapeutic anti-coagulation arm was stopped due to meeting a futility threshold and a potential for harm for this sub-group could not be excluded. Enrollment continues for moderately ill hospitalized COVID-19 patients.

• Based on a recommendation from the ACTIV4 DSMB on June 18, 2021, enrollment of patients not requiring ICU level of care and randomized to P2Y12 or standard care was stopped due to meeting a futility threshold. Enrollment continues for severely ill (ICU level of care) hospitalized COVID-19 patients.