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Trial record 1 of 1 for:    NCT04280705
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Adaptive COVID-19 Treatment Trial (ACTT)

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ClinicalTrials.gov Identifier: NCT04280705
Recruitment Status : Recruiting
First Posted : February 21, 2020
Last Update Posted : April 6, 2020
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief 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 75 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. Subjects will be assessed daily while hospitalized. Discharged subjects will be asked to attend study visits at Days 15 and 29. All subjects will undergo a series of efficacy, safety, and laboratory assessments. The primary objective of the study is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19.

Condition or disease Intervention/treatment Phase
Corona Virus Infection Other: Placebo Drug: Remdesivir Phase 3

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 75 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 calculated to be approximately 440 subjects, and if any additional therapeutic arms are added, the sample size will be recalculated. Subjects will be assessed daily while hospitalized. Discharged subjects will be asked to attend study visits at Days 15 and 29. All subjects will undergo a series of efficacy, safety, and laboratory assessments. The primary objective of the study is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19. The secondary objectives of the study are to 1) evaluate the clinical efficacy of different investigational therapeutics as compared to the control arm as assessed by clinical severity, hospitalization, and mortality, and 2) evaluate the safety of different investigational therapeutics as compared to the control arm.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 440 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults
Actual Study Start Date : February 21, 2020
Estimated Primary Completion Date : April 1, 2023
Estimated Study Completion Date : April 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo
200 mg of Remdesivir placebo administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir placebo for the duration of the hospitalization up to a 10 days total course. n=220.
Other: Placebo
The supplied matching placebo lyophilized formulation is identical in physical appearance to the active lyophilized formulation and contains the same inactive ingredients.

Experimental: Remdesivir
200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir for the duration of the hospitalization up to a 10 days total course. n=220.
Drug: Remdesivir
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.




Primary Outcome Measures :
  1. Percentage of subjects reporting each severity rating on an 8-point ordinal scale [ Time Frame: Day 15 ]
    The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.


Secondary Outcome Measures :
  1. Change from baseline in alanine transaminase (ALT) [ Time Frame: Day 1 through Day 29 ]
  2. Change from baseline in aspartate transaminase (AST) [ Time Frame: Day 1 through Day 29 ]
  3. Change from baseline in creatinine [ Time Frame: Day 1 through Day 29 ]
  4. Change from baseline in glucose [ Time Frame: Day 1 through Day 29 ]
  5. Change from baseline in hemoglobin [ Time Frame: Day 1 through Day 29 ]
  6. Change from baseline in platelets [ Time Frame: Day 1 through Day 29 ]
  7. Change from baseline in prothrombin time (PT) [ Time Frame: Day 1 through Day 29 ]
  8. Change from baseline in total bilirubin [ Time Frame: Day 1 through Day 29 ]
  9. Change from baseline in white blood cell count with differential [ Time Frame: Day 1 through Day 29 ]
  10. Change in National Early Warning Score (NEWS) from baseline [ Time Frame: Day 1 through Day 29 ]
    The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

  11. Clinical status using ordinal scale [ Time Frame: Day 3 through Day 29 ]
    The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

  12. Cumulative incidence of Grade 3 and 4 adverse events (AEs) [ Time Frame: Day 1 through Day 29 ]

    Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating.

    Grade 4 AEs are defined as events that are potentially life threatening.


  13. Cumulative incidence of serious adverse events (SAEs) [ Time Frame: Day 1 through Day 29 ]
    An SAE is defined as an AE or suspected adverse reaction is considered serious is, in the view of either the investigator or the sponsor, if results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.

  14. Discontinuation or temporary suspension of infusions [ Time Frame: Day 1 through Day 29 ]
    For any reason.

  15. Duration of hospitalization [ Time Frame: Day 1 through Day 29 ]
    Measured in days.

  16. Duration of new non-invasive ventilation or high flow oxygen use [ Time Frame: Day 1 through Day 29 ]
  17. Duration of new oxygen use [ Time Frame: Day 1 through Day 29 ]
  18. Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use [ Time Frame: Day 1 through Day 29 ]
  19. Incidence of new non-invasive ventilation or high flow oxygen use [ Time Frame: Day 1 through Day 29 ]
  20. Incidence of new oxygen use [ Time Frame: Day 1 through Day 29 ]
  21. Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use [ Time Frame: Day 1 through Day 29 ]
  22. Mean change in the ordinal scale [ Time Frame: Day 1 through Day 29 ]
    The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

  23. Number of non-invasive ventilation/high flow oxygen free days [ Time Frame: Day 1 to Day 29 ]
  24. Number of oxygenation free days [ Time Frame: Day 1 to Day 29 ]
  25. Subject 14-day mortality [ Time Frame: Day 1 through Day 15 ]
    Date and cause of death (if applicable).

  26. Subject 28-day mortality [ Time Frame: Day 1 through Day 29 ]
    Date and cause of death (if applicable).

  27. Time to an improvement of one category using an ordinal scale [ Time Frame: Day 1 through Day 29 ]
    The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

  28. Time to an improvement of two categories using an ordinal scale [ Time Frame: Day 1 through Day 29 ]
    The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

  29. Time to discharge or to a National Early Warning Score (NEWS) of </= 2 and maintained for 24 hours, whichever occurs first [ Time Frame: Day 1 through Day 29 ]
    The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

  30. Ventilator/extracorporeal membrane oxygenation (ECMO) free days [ Time Frame: Day 1 through Day 29 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Admitted to a hospital with symptoms suggestive of COVID-19 infection.
  2. Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
  3. Understands and agrees to comply with planned study procedures.
  4. Agrees to the collection of oropharyngeal (OP) swabs.
  5. Male or non-pregnant female adult > / = 18 years of age at time of enrollment.
  6. Has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay in any specimen collected < 72 hours prior to randomization.

    Note - 72 hours is not necessarily time from initial diagnosis. If > / = 72 hours since positive PCR, the PCR may be repeated to assess eligibility.

  7. Illness of any duration, and at least one of the following:

    • Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR
    • Clinical assessment (evidence of rales/crackles on exam) AND SpO2 < / = 94% on room air, OR
    • Requiring supplemental oxygen, OR
    • Requiring mechanical ventilation.
  8. 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.
  9. 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)/Aspartate Transaminase (AST) > 5 times the upper limit of normal.
  2. Estimated glomerular filtration rate (eGFR) < 50 or requiring dialysis.
  3. Pregnancy or breast feeding.
  4. Anticipated transfer to another hospital which is not a study site within 72 hours.
  5. Allergy to any study medication.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04280705


Contacts
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Contact: 20-0006 Central Contact 13017617948 DMIDClinicalTrials@niaid.nih.gov

Locations
Show Show 54 study locations
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT04280705    
Other Study ID Numbers: 20-0006
First Posted: February 21, 2020    Key Record Dates
Last Update Posted: April 6, 2020
Last Verified: March 20, 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Adaptive
COVID-19
Efficacy
Multicenter
novel coronavirus
Safety
Additional relevant MeSH terms:
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Coronavirus Infections
Severe Acute Respiratory Syndrome
Virus Diseases
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Respiratory Tract Infections
Respiratory Tract Diseases