Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 ACUTE

Trial ID or NCT#

NCT04505774

Status

not recruiting iconNOT RECRUITING

Purpose

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

Official Title

A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic and Additional Strategies in Hospitalized Adults With COVID-19

Eligibility Criteria

Ages Eligible for Study: Older than 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers: No
Inclusion Criteria:
  1. * ≥ 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:
  1. * Imminent death* Requirement for chronic mechanical ventilation via tracheostomy prior to hospitalization* Pregnancy
    1. Inclusion Criteria for Arm E
    2. Inclusion criteria contained in the master protocol in addition to the following:
    3. 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)
    4. For moderate illness severity, participants are required to meet one or more of the following risk criteria:
      1. 1. Age ≥ 65 years or2. ≥2 of the following -
  2. * 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
    1. Exclusion Criteria for Arm E
  3. * 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
    1. Inclusion Criteria for Arm F
    2. Inclusion criteria contained in the master protocol in addition to the following:
    3. 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)
    4. For moderate illness severity, participants are required to meet one or more of the following risk criteria:
      1. 1. Age ≥ 65 years or2. ≥2 of the following-
  4. * 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
    1. Exclusion Criteria for Arm F
    2. In addition to the exclusion criteria noted in the master protocol, arm-specific exclusion criteria are as follows:
  5. * 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
  6. * 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.
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Investigator(s)

Nidhi Rohatgi, MD MS
Nidhi Rohatgi, MD MS
Hospitalist
Clinical Professor, Medicine Clinical Professor (By courtesy), Neurosurgery Clinical Professor (By courtesy), Anesthesiology, Perioperative and Pain Medicine
Joseph Levitt, MD, MS
Joseph Levitt, MD, MS
Pulmonary critical care specialist, Pulmonologist, Critical care specialist
Associate Professor of Medicine (Pulmonary and Critical Care Medicine)

View on ClinicalTrials.gov