Phase 3
Completed N=1,033
Adaptive COVID-19 Treatment Trial 2 (ACTT-2)
Source: ClinicalTrials.gov NCT04401579 ↗Enrolled (actual)
1,033
Serious AEs
19.4%
Results posted
Apr 2021
Primary outcomePrimary: Time to Recovery — 7.0; 8.0 Days — p=0.047
◆ Published Evidence
Highly cited
1,912citations · ~382 / year
Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.
Summary
ACTT-2 will evaluate the combination of baricitinib and remdesivir compared to remdesivir alone. 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 and oropharyngeal (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, 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 outcome is time to recovery by Day 29.
Linked Publications (5)
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Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.
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SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19.
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Janus kinase inhibitors for the treatment of COVID-19.
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A Risk Profile Using Simple Hematologic Parameters to Assess Benefits From Baricitinib in Patients Hospitalized With COVID-19: A Post Hoc Analysis of the Adaptive COVID-19 Treatment Trial-2.
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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 Time to Recovery |
7.0; 8.0 | 0.047 sig |
| PRIMARY Time to Recovery by Race |
10; 10.0; 7.0; 6.0; 7.0; 7.0 | — |
| PRIMARY Time to Recovery by Ethnicity |
7.0; 9.0; 7.0; 7.0 | — |
| PRIMARY Time to Recovery by Sex |
7.0; 9.0; 7.0; 7.0 | — |
| SECONDARY Change From Baseline in Alanine Transaminase (ALT) |
3.3; 2.0; 16.8; 8.8; 7.9; 7.8 | — |
| SECONDARY Change From Baseline in Aspartate Transaminase (AST) |
3.1; 2.4; 27.4; 2.8; -5.6; -4.3 | — |
| SECONDARY Change From Baseline in Creatinine |
-0.036; -0.019; -0.078; 0.001; -0.082; 0.129 | — |
| SECONDARY Change From Baseline in Glucose |
-17.1; -6.0; -15.9; -1.6; -16.8; 5.0 | — |
| SECONDARY Change From Baseline in Hemoglobin |
-0.46; -0.34; -0.62; -0.64; -0.93; -1.08 | — |
| SECONDARY Change From Baseline in Platelets |
55.9; 52.6; 116.6; 106.1; 197.9; 158.9 | — |
| SECONDARY Change From Baseline in Prothrombin International Normalized Ratio (INR) |
-0.03; 0.05; 0.02; 0.08; 0.01; 0.08 | — |
| SECONDARY Change From Baseline in Total Bilirubin |
-0.06; -0.01; -0.04; 0.01; -0.06; 0.01 | — |
| SECONDARY Change From Baseline in White Blood Cell Count (WBC) |
-0.831; -0.037; -0.276; 0.392; 0.663; 1.606 | — |
| SECONDARY Change From Baseline in Neutrophils |
-1.925; -0.333; -1.334; -0.204; -0.813; 1.139 | — |
| SECONDARY Change From Baseline in Lymphocytes |
0.503; 0.074; 0.620; 0.205; 0.515; 0.304 | — |
| SECONDARY Change From Baseline in Monocytes |
0.004; 0.062; 0.094; 0.153; 0.105; 0.279 | — |
| SECONDARY Change From Baseline in Basophils |
0.000; 0.001; 0.007; 0.006; 0.011; 0.017 | — |
| SECONDARY Change From Baseline in Eosinophils |
0.050; 0.039; 0.104; 0.075; 0.088; 0.086 | — |
| SECONDARY Change in National Early Warning Score (NEWS) From Baseline |
-0.5; -0.1; -0.9; -0.4; -1.5; -0.8 | — |
| SECONDARY Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs) |
40.8; 46.8 | — |
| SECONDARY Percentage of Participants Reporting Serious Adverse Events (SAEs) |
16.0; 21.0 | — |
| SECONDARY Duration of Hospitalization |
8; 8; 8; 8 | — |
| SECONDARY Duration of New Non-invasive Ventilation or High Flow Oxygen Use |
6; 4.5; 5; 4 | — |
| SECONDARY Duration of New Oxygen Use |
3; 3; 3; 3 | — |
| SECONDARY Duration of New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use |
16; 27; 13; 20 | — |
| SECONDARY Duration of Oxygen Use |
10; 12; 9; 10 | — |
| SECONDARY Percentage of Participants Discontinued or Temporarily Suspended From Investigational Therapeutics |
55; 51; 0; 1; 66; 59 | — |
| SECONDARY Percentage of Participants Requiring New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use |
10; 15 | — |
| SECONDARY Percentage of Participants Requiring New Oxygen Use |
23; 40 | — |
| SECONDARY Mean Change in the Ordinal Scale |
0.1; 0.1; 0.0; 0.0; -0.3; -0.1 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 15 |
2; 3; 9; 16; 4; 4 | 0.44 |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 1 |
0; 0; 10; 11; 20; 22 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 3 |
0.4; 0; 15; 16; 22; 22 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 5 |
1; 0; 15; 18; 17; 18 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 8 |
1; 1; 13; 18; 11; 12 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 11 |
1; 2; 11; 16; 6; 7 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 22 |
4; 6; 6; 9; 3; 1 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 29 |
5; 7; 3; 7; 2; 1 | — |
| SECONDARY 14-day Participant Mortality |
0.02; 0.03 | — |
| SECONDARY 28-day Participant Mortality |
0.05; 0.08 | — |
| SECONDARY Time to an Improvement of One Category Using an Ordinal Scale |
6.0; 8.0 | 0.002 sig |
| SECONDARY Time to an Improvement of Two Categories Using an Ordinal Scale |
12.0; 13.0 | 0.005 sig |
| SECONDARY Time to Discharge or to a NEWS of 2 or Less and Maintained for 24 Hours, Whichever Occurs First |
6.0; 7.0 | 0.003 sig |
| SECONDARY Change From Baseline in C-reactive Protein (CRP) |
-23.035; -18.671; -58.935; -30.908; -78.411; -62.038 | — |
| SECONDARY Change From Baseline in D-dimer Concentration |
-0.374; 0.384; 0.053; -0.149; -0.271; 0.351 | — |
Eligibility Criteria
Inclusion Criteria
- Admitted to a hospital with symptoms suggestive of COVID-19.
- 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 of 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) /= 20 mg/day of prednisone or equivalent for >/=14 consecutive days in the 4 weeks prior to screening.
- Use of probenecid that cannot be discontinued at study enrollment.
- Have diagnosis of current active tuberculosis (TB) or, if known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening required).
- Suspected serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking investigational product.
- 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 is allowed for all subjects.
- Have a history of VTE (deep vein thrombosis [DVT] or pulmonary embolism [PE]) within 12 weeks prior to screening or have a history of recurrent (>1) VTE (DVT/PE).
- Immunocompromised patients, patients with a chronic medical condition, or those taking a medication that cannot be discontinued at enrollment, who, in the judgment of PI, are at increased risk for serious infections or other safety concerns given the study products.
Data sourced from ClinicalTrials.gov (NCT04401579) 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.