ACTIV-3b: Therapeutics for Severely Ill Inpatients With COVID-19

• Status: Recruiting
• Trial end date: 2023-04-01
• Target enrollment: 0
• Participant gender: All

Summary

This study looks at the safety and effectiveness of different drugs in treating COVID-19 in people who have been hospitalized with the infection and who have acute respiratory failure. Participants in the study will be treated with either a study drug plus current standard of care (SOC), or with placebo plus current SOC.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: AIDS Clinical Trials Group; Cardiothoracic Surgical Trials Network (CTSN); Gilead Sciences; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT); Kirby Institute; Medical Research Council; National Heart, Lung, and Blood Institute (NHLBI); NeuroRx, Inc.; Prevention and Early Treatment of Acute Lung Injury (PETAL); University of Copenhagen; US Department of Veterans Affairs; Washington D.C. Veterans Affairs Medical Center
• Treatments: Phentolamine; Remdesivir; Vasoactive Intestinal Peptide

Criteria

Inclusion Criteria:

• Signed informed consent.

• Requiring admission to hospital for acute medical care (not for purely public health or quarantine purposes).

• Current respiratory failure (i.e. receipt of high-flow nasal cannula, non-invasive ventilation, invasive mechanical ventilation, or ECMO (extracorporeal membrane oxygenation) used to treat acute hypoxemic respiratory failure).

• SARS-CoV-2 (COVID-19) infection, documented by a nucleic acid test (NAT) or equivalent testing with most recent rest within 14 days prior to randomization.

• Respiratory failure is believed to be due to SARS-CoV-2 pneumonia.

Exclusion Criteria:

• Known allergy to investigational agent or vehicle.

• More than 4 days since initiation of support for respiratory failure.

• Chronic/home mechanical ventilation (invasive or non-invasive) for chronic lung or neuromuscular disease (non-invasive ventilation used solely for sleep-disordered breathing is not an exclusion).

• Moribund patient (i.e. not expected to survive 24 hours).

• Active use of "comfort care" or other hospice-equivalent standard of care.

• Expected inability to participate in study procedures.

• In the opinion of the investigator, any condition for which, participation would not be in the best interest of the participant or that could limit protocol-specified assessments.

• Previous enrollment in TESICO

Agent-specific exclusion criteria

• Prior receipt of any dose of remdesivir during present illness (remdesivir agent).

• GFR (glomerular filtration rate) < 30 ml/min and not receiving dialysis (remdesivir agent).

• ALT (alanine aminotransferase) or AST (aspartate aminotransferase) > 10 times upper limit of normal (remdesivir agent).

• Unwillingness to commit to avoid sex that may result in pregnancy for at least 7 days after completion of remdesivir vs. placebo (remdesivir agent).

• Refractory hypotension (aviptadil agent).

• Severe diarrhea (Aviptadil agent).

• Current C. difficile infection (aviptadil agent).

• Pregnancy or current breast-feeding (aviptadil agent).

• End-stage liver disease (aviptadil agent).