Adaptive COVID-19 Treatment Trial (ACTT)
Condition: COVID-19
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 3

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.
    

Detailed description: 
      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.

      The initial sample size is projected to be 572 subjects to achieve 400 subjects with a
      "recovered" status (per the primary objective). The primary analysis will be based on those
      subjects enrolled in order to 400 recoveries. An additional analysis of the moderate severity
      subgroup (those with baseline status of "Hospitalized, requiring supplemental oxygen" or
      "Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care") is also
      of public health importance. Hence, enrollment will be permitted until the date of April 20,
      2020 to ensure 400 recoveries and provide additional data about this important subgroup. With
      recent enrollment rates, the total sample size may be 600 to over 800.

      Subjects will be assessed daily while hospitalized. If the subjects are discharged from the
      hospital, they will have a study visit at Days 15, 22, and 29 as an outpatient. For
      discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain
      safety laboratory tests and OP swab and blood (serum only) samples for secondary research as
      well as clinical outcome data. However, infection control or other restrictions may limit the
      ability of the subject to return to the clinic. In this case, Day 15 and 29 visits may be
      conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have
      laboratory tests or collection of samples and may also be conducted by phone.

      All subjects will undergo a series of efficacy, safety, and laboratory assessments. Safety
      laboratory tests and blood (serum and plasma) research samples and oropharyngeal (OP) swabs
      will be obtained on Days 1 (prior to infusion) and Days 3, 5, 8, and 11 (while hospitalized).
      OP swabs and blood (serum only) plus safety laboratory tests will be collected on Day 15 and
      29 (if the subject attends an in-person visit or are still hospitalized).

      The primary outcome is time to recovery by Day 29. A key secondary outcome evaluates
      treatment-related improvements in the 8-point ordinal scale at Day 15. As little is known
      about the clinical course of COVID-19, a pilot study will be used for a blinded sample size
      reassessment.

      Contacts:

      20-0006 Central Contact

      Telephone: 1 (301) 7617948

      Email: DMIDClinicalTrials@niaid.nih.gov
    

Intervention name(s): Placebo; Remdesivir
Intervention type(s): Other; Drug
Intervention description(s): 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
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Adaptive; COVID-19; Efficacy; Multicenter; novel coronavirus; Safety; ACTT