Status:
COMPLETED
Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 ACUTE
Lead Sponsor:
Matthew Neal MD
Collaborating Sponsors:
National Heart, Lung, and Blood Institute (NHLBI)
Conditions:
Covid19
Eligibility:
All Genders
18+ years
Phase:
PHASE4
Brief 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
Detailed Description
The severe acute respiratory syndrome coronavirus 2, which causes the highly contagious coronavirus disease 2019 (COVID-19), has resulted in a global pandemic. The clinical spectrum of COVID-19 infec...
Eligibility Criteria
Inclusion
- ≥ 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
- 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:
- 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
- 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:
- 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
- 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.
Key Trial Info
Start Date :
September 4 2020
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
January 26 2024
Estimated Enrollment :
3591 Patients enrolled
Trial Details
Trial ID
NCT04505774
Start Date
September 4 2020
End Date
January 26 2024
Last Update
December 30 2024
Active Locations (101)
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1
University of Alabama
Birmingham, Alabama, United States, 35233
2
University of Arizona
Tucson, Arizona, United States, 85719
3
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
4
Kaiser Permanente Fontana
Fontana, California, United States, 92335