Adaptive COVID-19 Treatment Trial (ACTT)
Condition: COVID-19
MeSH terms: COVID-19
Intervention: Placebo; Remdesivir
Intervention description: The supplied placebo lyophilized formulation is identical in physical appearance to the active lyophilized formulation and contains the same inactive ingredients. Alternatively, a placebo of normal saline of equal volume may be given if there are limitations on matching placebo supplies.; Drug Remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524. In addition to the active ingredient, the lyophilized formulation of Remdesivir contains the following inactive ingredients: water for injection, sulfobutylether beta-cyclodextrin sodium (SBECD), and hydrochloric acid and/or sodium hydroxide.
Intervention MeSH terms: Remdesivir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1062.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Adaptive; COVID-19; Efficacy; Multicenter; novel coronavirus; Safety; ACTT

Summary:

      This study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the
      safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with
      COVID-19. The study is a multicenter trial that will be conducted in up to approximately 100
      sites globally. The study will compare different investigational therapeutic agents to a
      control arm. There will be interim monitoring to introduce new arms and allow early stopping
      for futility, efficacy, or safety. If one therapy proves to be efficacious, then this
      treatment may become the control arm for comparison(s) with new experimental treatment(s).
      Any such change would be accompanied by an updated sample size. Because background standards
      of supportive care may evolve/improve over time as more is learned about successful
      management of COVID-19, comparisons of safety and efficacy will be based on data from
      concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will
      actively monitor interim data to make recommendations about early study closure or changes to
      study arms. To evaluate the clinical efficacy, as assessed by time to recovery, of different
      investigational therapeutics as compared to the control arm.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Admitted to a hospital with symptoms suggestive of COVID-19 infection.

          2. Subject (or legally authorized representative) provides informed consent prior to
             initiation of any study procedures.

          3. Subject (or legally authorized representative) understands and agrees to comply with
             planned study procedures.

          4. Male or non-pregnant female adult > / = 18 years of age at time of enrollment.

          5. Has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain
             reaction (PCR) or other commercial or public health assay in any specimen, as
             documented by either or the following:

               1. PCR positive in sample collected < 72 hours prior to randomization; OR

                  Exclusion Criteria:

               2. PCR positive in sample collected >/= 72 hours prior to randomization, documented
                  inability to obtain a repeat sample (e.g. due to lack of testing supplies,
                  limited testing capacity, results taking >24 hours, etc.) AND progressive disease
                  suggestive of ongoing SARS-CoV-2 infection.

          6. Illness of any duration, and at least one of the following:

               1. Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR

               2. SpO2 < / = 94% on room air, OR

               3. Requiring supplemental oxygen, OR

               4. Requiring mechanical ventilation.

          7. Women of childbearing potential must agree to either abstinence or use at least one
             primary form of contraception not including hormonal contraception from the time of
             screening through Day 29.

          8. Agrees to not participate in another clinical trial for the treatment of COVID-19 or
             SARS-CoV-2 through Day 29.

        Exclusion Criteria:

          1. Alanine Transaminase (ALT) or Aspartate Transaminase (AST) > 5 times the upper limit
             of normal.

          2. Estimated glomerular filtration rate (eGFR) < 30 ml/min (including patients receiving
             hemodialysis or hemofiltration).

          3. Pregnancy or breast feeding.

          4. Anticipated discharge from the hospital or transfer to another hospital which is not a
             study site within 72 hours.

          5. Allergy to any study medication.