Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 ACUTE
Source: ClinicalTrials.gov NCT04505774 ↗Summary
Linked Publications (5)
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Effect of the P-Selectin Inhibitor Crizanlizumab on Survival Free of Organ Support in Patients Hospitalized for COVID-19: A Randomized Controlled Trial.
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Effect of sodium-glucose co-transporter-2 inhibitors on survival free of organ support in patients hospitalised for COVID-19 (ACTIV-4a): a pragmatic, multicentre, open-label, randomised, controlled, platform trial.
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Antiplatelet agents for the treatment of adults with COVID-19.
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Symptoms and Impaired Quality of Life After COVID-19 Hospitalization: Effect of Therapeutic Heparin in Non-ICU Patients in the Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 Acute Trial: Effect on 3-Month Symptoms and Quality of Life.
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Soluble Thrombomodulin Links Viremia and Mortality During COVID-19: Results From the ACTIV-4a Trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 21 Day Organ Support (Respiratory or Vasopressor) Free Days |
22; 22; 17; 17; 22; 22 | .6778 |
| SECONDARY Death Within 28 Days |
39; 52; 120; 114; 37; 42 | .1959 |
| SECONDARY Acute Kidney Injury |
0; 0; 38; 36; 5; 5 | 1.0 |
| SECONDARY Major Thrombotic Event or in Hospital Death |
450; 462; 174; 177; 28; 33 | .0577 |
| SECONDARY Any Thrombotic Event or in Hospital Death |
450; 463; 187; 177; 28; 33 | .0732 |
| SECONDARY Any Renal Replacement Therapy |
12; 12; 37; 36; 1; 1 | .8837 |
| SECONDARY Days Free of Organ Support and Renal Replacement Therapy |
29; 29; 24; 24; 29; 29 | .6636 |
| SECONDARY Ventilator Free Days up to Day 28 |
24.89; 24.63; 21.09; 20.83; 26.22; 26.42 | .6780 |
| SECONDARY Days Free of Vasopressors |
29; 29; 29; 29; 29; 29 | .4016 |
| SECONDARY Progression to Intubation or Death |
450; 463; 768; 735; 273; 278 | .3135 |
| SECONDARY Survival Until Discharge |
406; 409; 633; 598; 264; 266 | .3575 |
Eligibility 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:
- 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 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.
Data sourced from ClinicalTrials.gov (NCT04505774) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.