Phase 3
N=1,062
Adaptive COVID-19 Treatment Trial (ACTT)
COVID-19
Bottom Line
View on ClinicalTrials.gov: NCT04280705 ↗Enrolled (actual)
1,062
Serious AEs
28.1%
Results posted
Sep 2020
Primary outcome: Primary: Time to Recovery — 15; 10 Days — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Placebo (Other); Remdesivir (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Primary completion
- May 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to Recovery |
15; 10 | <0.001 sig |
| PRIMARY Time to Recovery by Race |
12.0; 11.0; 15.0; 10.0; 15.0; 9.0 | — |
| PRIMARY Time to Recovery by Ethnicity |
15.0; 10.0; 12.5; 10.0 | — |
| PRIMARY Time to Recovery by Sex |
15.0; 9.0; 15.0; 10.0 | — |
| SECONDARY Change From Baseline in Alanine Transaminase (ALT) |
14.3; 2.9; 23.1; 10.8; 24.2; 8.9 | — |
| SECONDARY Change From Baseline in Aspartate Transaminase (AST) |
13.7; -2.0; 12.8; 6.0; 13.1; 1.1 | — |
| SECONDARY Change From Baseline in Creatinine |
0.037; 0.038; -0.695; 0.075; -0.882; 0.158 | — |
| SECONDARY Change From Baseline in Glucose |
-0.2; -3.0; 6.3; 2.1; 2.2; 3.2 | — |
| SECONDARY Change From Baseline in Hemoglobin |
-0.52; -0.69; -0.83; -0.99; -1.22; -0.49 | — |
| SECONDARY Change From Baseline in Platelets |
39.3; 46.0; 76.5; 90.1; 111.8; 130.8 | — |
| SECONDARY Change From Baseline in Prothrombin Time (PT) |
-0.18; 0.44; -0.30; 1.15; 0.01; 1.43 | — |
| SECONDARY Change From Baseline in Total Bilirubin |
0.08; -0.04; 0.58; -0.03; 0.22; 0.01 | — |
| SECONDARY Change From Baseline in White Blood Cell Count (WBC) |
18.691; -18.970; 9.886; -28.209; 27.223; -45.997 | — |
| SECONDARY Change From Baseline in Neutrophils |
9.429; -8.093; 4.177; -15.067; 17.916; -28.179 | — |
| SECONDARY Change From Baseline in Lymphocytes |
5.883; -7.847; 4.064; -11.723; 8.006; -15.455 | — |
| SECONDARY Change From Baseline in Monocytes |
2.448; -2.940; 1.498; -2.628; 2.324; -3.645 | — |
| SECONDARY Change From Baseline in Basophils |
0.020; 0.005; 0.038; 0.005; 0.196; 0.005 | — |
| SECONDARY Change From Baseline in Eosinophils |
0.634; 0.016; 0.666; -0.066; 0.596; -0.221 | — |
| SECONDARY Change in National Early Warning Score (NEWS) From Baseline |
0.1; -0.3; 0.3; -0.4; -0.3; -0.5 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 1 |
0; 0; 30; 24; 19; 18 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 3 |
1; 1; 36; 28; 17; 16 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 5 |
2; 2; 37; 28; 14; 12 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 8 |
7; 3; 33; 24; 9; 9 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 11 |
8; 4; 28; 22; 7; 6 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 15 |
11; 6; 22; 15; 4; 4 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 22 |
13; 9; 14; 9; 2; 2 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 29 |
15; 11; 9; 6; 2; 1 | — |
| SECONDARY Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs) |
57; 51 | 0.058 |
| SECONDARY Percentage of Participants Reporting Serious Adverse Events (SAEs) |
32; 24 | 0.010 sig |
| SECONDARY Percentage of Participants Discontinued or Temporarily Suspended From Investigational Therapeutics |
30; 41; 4; 3; 2; 2 | — |
| SECONDARY Duration of Hospitalization |
17; 12; 14; 10 | — |
| SECONDARY Duration of New Non-invasive Ventilation or High Flow Oxygen Use |
4; 3; 3; 3 | — |
| SECONDARY Duration of New Oxygen Use |
5.5; 4; 3; 3.5 | — |
| SECONDARY Duration of New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use |
23; 21.5; 16; 14 | — |
| SECONDARY Percentage of Participants Requiring New Non-invasive Ventilation or High-flow Oxygen Use |
24; 17 | — |
| SECONDARY Percentage of Participants Requiring New Oxygen Use |
44; 36 | — |
| SECONDARY Percentage of Participants Requiring New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use |
23; 13 | — |
| SECONDARY Mean Change in the Ordinal Scale |
0.2; 0.1; 0.1; 0.0; 0.0; -0.2 | — |
| SECONDARY 14-day Participant Mortality |
0.12; 0.07 | — |
| SECONDARY 29-day Participant Mortality |
0.15; 0.11 | — |
| SECONDARY Time to an Improvement by at Least One Category Using an Ordinal Scale |
9; 7 | 0.002 sig |
| SECONDARY Time to an Improvement of at Least Two Categories Using an Ordinal Scale |
14; 11 | <0.001 sig |
| SECONDARY Time to Discharge or to a NEWS of 2 or Less and Maintained for 24 Hours, Whichever Occurs First |
12; 8 | <0.001 sig |
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
- Admitted to a hospital with symptoms suggestive of COVID-19 infection.
- Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures.
- Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
- Male or non-pregnant female adult > / = 18 years of age at time of enrollment.
- 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:
- 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.
- Illness of any duration, and at least one of the following:
- Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR
- SpO2 5 times the upper limit of normal.
- Estimated glomerular filtration rate (eGFR) < 30 ml/min (including patients receiving hemodialysis or hemofiltration).
- Pregnancy or breast feeding.
- Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours.
- Allergy to any study medication.
Data sourced from ClinicalTrials.gov (NCT04280705). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.