Phase 3
Completed N=1,010
Adaptive COVID-19 Treatment Trial 4 (ACTT-4)
COVID-19
Source: ClinicalTrials.gov NCT04640168 ↗
Enrolled (actual)
1,010
Serious AEs
19.2%
Results posted
Jun 2022
Primary outcomePrimary: The Proportion of Participants Not Meeting Criteria for One of the Following Two Ordinal Scale Categories at Any Time: 8) Death; 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) — 0.87; 0.88 Proportion of participants — p=0.909
◆ Published Evidence
Highly cited
152citations · ~30 / year
SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19.
Summary
ACTT-4 will evaluate the combination of baricitinib and remdesivir compared to dexamethasone and remdesivir. 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. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests, oropharyngeal (OP) swabs, plasma (Day 29), and serum for secondary research as well as clinical outcome data. However, if infection control or other restrictions limit the ability of the subject to return to the clinic, these 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 is conducted by phone. The primary objective is to evaluate the clinical efficacy of baricitinib + remdesivir versus dexamethasone + remdesivir as assessed by the mechanical ventilation free survival by Day 29.
Linked Publications (3)
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SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19.
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Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial.
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Temporal Improvements in COVID-19 Outcomes for Hospitalized Adults: A Post Hoc Observational Study of Remdesivir Group Participants in the Adaptive COVID-19 Treatment Trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY The Proportion of Participants Not Meeting Criteria for One of the Following Two Ordinal Scale Categories at Any Time: 8) Death; 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) |
0.87; 0.88 | 0.909 |
| PRIMARY The Proportion of Participants Not Meeting Criteria for One of the Following Two Ordinal Scale Categories at Any Time: 8) Death; 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) by Race |
0.76; 0.88; 0.91; 0.86; 0.87; 0.88 | — |
| PRIMARY The Proportion of Participants Not Meeting Criteria for One of the Following Two Ordinal Scale Categories at Any Time: 8) Death; 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) by Ethnicity |
0.87; 0.87; 0.88; 0.87 | — |
| PRIMARY The Proportion of Participants Not Meeting Criteria for One of the Following Two Ordinal Scale Categories at Any Time: 8) Death; 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) by Sex |
0.86; 0.87; 0.89; 0.88 | — |
| SECONDARY Change From Baseline in Alanine Aminotransferase (ALT) |
1.1; 4.3; 6.0; 15.9; 4.7; 16.1 | — |
| SECONDARY Change From Baseline in Aspartate Aminotransferase (AST) |
-5.9; -7.2; -4.0; -8.5; -10.8; -12.0 | — |
| SECONDARY Change From Baseline in C-reactive Protein (CRP) |
-41.1; -61.0; -39.4; -73.6; -53.0; -79.0 | — |
| SECONDARY Change From Baseline in Creatinine |
-0.207; -0.081; -0.287; -0.122; -0.434; -0.096 | — |
| SECONDARY Change From Baseline in D-dimer Concentration |
0.8; 0.2; 0.7; 0.7; 0.7; 0.9 | — |
| SECONDARY Change From Baseline in Glucose |
-46.9; 3.8; -43.2; -6.7; -35.0; -9.6 | — |
| SECONDARY Change From Baseline in Hemoglobin |
-0.51; -0.25; -0.64; -0.13; -1.08; -0.15 | — |
| SECONDARY Change From Baseline in Platelets |
53.1; 70.4; 107.4; 117.6; 178.9; 140.4 | — |
| SECONDARY Change From Baseline in Prothrombin International Normalized Ratio (INR) |
0.06; -0.01; 0.11; -0.03; 0.11; -0.08 | — |
| SECONDARY Change From Baseline in Total Bilirubin |
0.00; -0.09; 0.06; -0.03; 0.03; 0.03 | — |
| SECONDARY Change From Baseline in White Blood Cell Count (WBC) |
0.433; 1.292; 1.358; 2.072; 2.629; 4.048 | — |
| SECONDARY Change From Baseline in Neutrophils |
-0.500; 0.974; 0.356; 1.407; 1.421; 3.227 | — |
| SECONDARY Change From Baseline in Lymphocytes |
0.766; 0.142; 0.627; 0.356; 0.614; 0.317 | — |
| SECONDARY Change From Baseline in Monocytes |
0.114; 0.120; 0.164; 0.180; 0.257; 0.221 | — |
| SECONDARY Change From Baseline in Basophils |
0.008; 0.000; 0.016; 0.004; 0.015; 0.006 | — |
| SECONDARY Change From Baseline in Eosinophils |
0.034; -0.006; 0.104; 0.006; 0.115; 0.027 | — |
| SECONDARY Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs) |
28.4; 36.1 | — |
| SECONDARY Percentage of Participants Reporting Serious Adverse Events (SAEs) |
18.9; 19.5 | — |
| SECONDARY Days of Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) |
27; 28; 14; 15 | — |
| SECONDARY Days of Non-invasive Ventilation/High Flow Oxygen |
5; 8; 4; 6 | — |
| SECONDARY Duration of Supplemental Oxygen Use |
10; 10.5; 9; 8 | — |
| SECONDARY Desirability of Outcome Ranking (DOOR) at Day 15 |
76; 77; 3; 1; 1; 2 | — |
| SECONDARY Desirability of Outcome Ranking (DOOR) at Day 29 |
85; 84; 0.002; 0.002; 1; 1 | — |
| SECONDARY Duration of Hospitalization |
7; 6; 6; 6 | — |
| SECONDARY Number of Participants With Discontinuation or Temporary Suspension of Study Product Administration |
460; 444; 486; 452; 410; 387 | — |
| SECONDARY 14-day Participant Mortality |
0.03; 0.02 | — |
| SECONDARY 28-day Participant Mortality |
0.05; 0.06 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 1 |
0.2; 0.0; 0.0; 0.0; 16.1; 14.2 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 3 |
0.4; 0.4; 3.1; 1.0; 22.1; 21.5 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 5 |
0.6; 0.4; 5.2; 3.4; 19.4; 20.9 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 8 |
1.2; 0.8; 7.4; 6.1; 12.2; 14.6 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 11 |
2.1; 1.2; 7.8; 6.9; 6.6; 9.1 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 15 |
3.1; 2.6; 6.2; 6.1; 3.7; 5.3 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 22 |
4.9; 4.9; 4.3; 4.9; 2.1; 2.8 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 29 |
5.4; 6.9; 2.7; 2.6; 2.3; 2.6 | — |
| SECONDARY Percentage of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories |
3; 3; 6; 6; 4; 5 | — |
| SECONDARY The Proportion of Participants Not Meeting Criteria for One of the Three Most Severe Ordinal Scale Categories at Any Time. |
0.81; 0.78 | — |
| SECONDARY Time to an Improvement of One Category From Baseline Using an Ordinal Scale |
5.0; 4.0 | — |
| SECONDARY Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale |
6.0; 5.0 | — |
| SECONDARY Time to Recovery |
6.0; 5.0 | — |
Eligibility Criteria
Inclusion Criteria
- Hospitalized with symptoms suggestive of COVID-19.
- Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures and understands and agrees to comply with planned study procedures.
- Male or non-pregnant female adult > / = 18 years of age at time of enrollment.
- Illness of any duration and has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay (e.g. NAAT, antigen test) in any respiratory specimen or saliva / = 20 mg/day of prednisone po or IV (or equivalent for other glucocorticoids) for > / = 14 consecutive days in the 4 weeks prior to screening.
- Have diagnosis of current active or latent tuberculosis (TB), if known, treated for less than 4 weeks with appropriate therapy (by history only, no screening required).
- Serious infection (besides COVID-19), immunosuppressive state, or immunosuppressive medications that in the opinion of the investigator could constitute a risk when taking baricitinib or dexamethasone.
- Have received any live vaccine (that is, live attenuated) within 4 weeks before screening, or intend to receive a live vaccine (or live attenuated) during the study. Note: Use of non-live (inactivated) vaccinations including SARS-CoV-2 vaccine is allowed for all subjects.
- Had a known Venous thromboembolism (VTE)(deep vein thrombosis [DVT] or pulmonary embolism [PE]) during the current COVID-19 illness.
Data sourced from ClinicalTrials.gov (NCT04640168) and the linked publication. 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. Informational only — not medical advice.