Clinical Data
ACTT-2 Trial Design
The Adaptive COVID-19 Treatment Trial 2 (ACTT-2) study was a randomized, double-blind, placebo-controlled clinical trial of hospitalized adults with confirmed SARS-CoV-2 infection that compared treatment with baricitinib and remdesivir (combination group; n=515) to treatment with placebo and remdesivir (placebo group; n=518). Patients had to have laboratory-confirmed SARS-CoV-2 infection, as well as at least one of the following to be enrolled in the trial: radiographic infiltrates by imaging, SpO2 ≤94% on room air, a requirement for supplemental oxygen, or a requirement for mechanical ventilation.
Patients treated with the combination received the following regimen:
- Baricitinib 4 mg once daily (orally) for 14 days or until hospital discharge.
- Remdesivir 200 mg on Day 1 and 100 mg once daily (via intravenous infusion) on subsequent days for a total treatment duration of 10 days or until hospital discharge.
The primary endpoint, for the intent to treat population, was time to recovery within 29 days after randomization.
Recovery was defined as:
- Being discharged from the hospital without limitations on activities,
- Being discharged from the hospital with limitations on activities and/or requiring home oxygen, or
- Hospitalized but not requiring supplemental oxygen and no longer requiring medical care.
The key secondary endpoint was clinical status on Day 15, as assessed on an 8-point ordinal scale (OS).
SELECT IMPORTANT SAFETY INFORMATION RELATED TO SERIOUS INFECTIONS AND THROMBOSIS
Serious Infections: Serious infections have occurred in patients receiving baricitinib. Avoid the use of baricitinib with known active tuberculosis. Consider if the potential benefits outweigh the potential risks of baricitinib treatment in patients with active serious infections other than COVID-19 or chronic/recurrent infections.
Thrombosis: In hospitalized patients with COVID-19, prophylaxis for venous thromboembolism is recommended unless contraindicated. If clinical features of deep vein thrombosis or pulmonary embolism occur, patients should be evaluated promptly and treated appropriately.
ACTT-2 Ordinal Scale
Patient Characteristics for ACTT-2
Patient Characteristics
| All subjects (N=1033) | BARI + RDV (n=515) | PBO + RDV (n=518) | |
|---|---|---|---|
| Age | |||
| Mean, years (SD) | All subjects (N=1033): 55.4 (15.7) | BARI + RDV (n=515): 55.0 (15.4) | PBO + RDV (n=518): 55.8 (16.0) |
| Distribution, n (%) | |||
| <40 years | All subjects (N=1033): 173 (16.7) | BARI + RDV (n=515): 87 (16.9) | PBO + RDV (n=518): 86 (16.6) |
| 40-64 years | All subjects (N=1033): 555 (53.7) | BARI + RDV (n=515): 281 (54.6) | PBO + RDV (n=518): 274 (52.9) |
| ≥65 years | All subjects (N=1033): 305 (29.5) | BARI + RDV (n=515): 147 (28.5) | PBO + RDV (n=518): 158 (30.5) |
| All subjects (N=1033) | BARI + RDV (n=515) | PBO + RDV (n=518) | |
|---|---|---|---|
| Sex, n (%) | |||
| Male | All subjects (N=1033): 652 (63.1) | BARI + RDV (n=515): 319 (61.9) | PBO + RDV (n=518): 333 (64.3) |
| Female | All subjects (N=1033): 381 (36.9) | BARI + RDV (n=515): 196 (38.1) | PBO + RDV (n=518): 185 (35.7) |
| All subjects (N=1033) | BARI + RDV (n=515) | PBO + RDV (n=518) | |
|---|---|---|---|
| Race, n (%)a | |||
| Asian | All subjects (N=1033): 101 (9.8) | BARI + RDV (n=515): 49 (9.5) | PBO + RDV (n=518): 52 (10.0) |
| Black | All subjects (N=1033): 156 (15.1) | BARI + RDV (n=515): 77 (15.0) | PBO + RDV (n=518): 79 (15.3) |
| White | All subjects (N=1033): 496 (48.0) | BARI + RDV (n=515): 251 (48.7) | PBO + RDV (n=518): 245 (47.3) |
| Other or Unknown | All subjects (N=1033): 280 (27.1) | BARI + RDV (n=515): 138 (26.8) | PBO + RDV (n=518): 142 (27.4) |
| Ethnic group, n (%)a | |||
| Hispanic or Latino | All subjects (N=1033): 531 (51.4) | BARI + RDV (n=515): 263 (51.1) | PBO + RDV (n=518): 268 (51.7) |
| Not Hispanic or Latino | All subjects (N=1033): 486 (47.0) | BARI + RDV (n=515): 246 (47.8) | PBO + RDV (n=518): 240 (46.3) |
| Not reported or unknown | All subjects (N=1033): 16 (1.5) | BARI + RDV (n=515): 6 (1.2) | PBO + RDV (n=518): 10 (1.9) |
aRace and ethnic group were reported by the patients. With respect to “other” race, the categories that were used when data on race were reported included American Indian or Alaska Native and Native Hawaiian or other Pacific Islander.
| All subjects (N=1033) | BARI + RDV (n=515) | PBO + RDV (n=518) | |
|---|---|---|---|
| Comorbidities as baseline, n (%)b | |||
| Obesity | All subjects (N=1033): 567 (56) | BARI + RDV (n=515): 295 (58) | PBO + RDV (n=518): 272 (53) |
| Hypertension | All subjects (N=1033): 522 (52) | BARI + RDV (n=515): 258 (51) | PBO + RDV (n=518): 264 (52) |
| Type 2 diabetes | All subjects (N=1033): 370 (37) | BARI + RDV (n=515): 195 (39) | PBO + RDV (n=518): 175 (35) |
| Coronary artery disease | All subjects (N=1033): 101 (10) | BARI + RDV (n=515): 50 (10) | PBO + RDV (n=518): 51 (10) |
| Asthma | All subjects (N=1033): 97 (10) | BARI + RDV (n=515): 53 (10) | PBO + RDV (n=518): 44 (9) |
| Chronic respiratory disease | All subjects (N=1033): 69 (7) | BARI + RDV (n=515): 39 (8) | PBO + RDV (n=518): 30 (6) |
| Chronic kidney disease | All subjects (N=1033): 64 (6) | BARI + RDV (n=515): 31 (6) | PBO + RDV (n=518): 33 (7) |
| Congestive heart failure | All subjects (N=1033): 62 (6) | BARI + RDV (n=515): 31 (6) | PBO + RDV (n=518): 31 (6) |
| Cancer | All subjects (N=1033): 37 (4) | BARI + RDV (n=515): 20 (4) | PBO + RDV (n=518): 17 (3) |
| Immune deficiency | All subjects (N=1033): 30 (3) | BARI + RDV (n=515): 17 (3) | PBO + RDV (n=518): 13 (3) |
| Chronic liver disease | All subjects (N=1033): 28 (3) | BARI + RDV (n=515): 13 (3) | PBO + RDV (n=518): 15 (3) |
| Any history of DVT or PE | All subjects (N=1033): 22 (2) | BARI + RDV (n=515): 11 (2) | PBO + RDV (n=518): 11 (2) |
| Cardiac valvular disease | All subjects (N=1033): 22 (2) | BARI + RDV (n=515): 10 (2) | PBO + RDV (n=518): 12 (2) |
| Chronic oxygen requirement | All subjects (N=1033): 17 (2) | BARI + RDV (n=515): 8 (2) | PBO + RDV (n=518): 9 (2) |
| Type 1 diabetes | All subjects (N=1033): 10 (1) | BARI + RDV (n=515): 5 (1) | PBO + RDV (n=518): 5 (1) |
| Coagulopathy | All subjects (N=1033): 7 (1) | BARI + RDV (n=515): 3 (1) | PBO + RDV (n=518): 4 (1) |
| Summary of coexisting conditions, n/total n (%)2 | |||
| None | All subjects (N=1033): 155/994 (15.6) | BARI + RDV (n=515): 64/496 (12.9) | PBO + RDV (n=518): 91/498 (18.3) |
| One | All subjects (N=1033): 270/994 (27.2) | BARI + RDV (n=515): 148/496 (29.8) | PBO + RDV (n=518): 122/498 (24.5) |
| Two or more | All subjects (N=1033): 569/994 (57.2) | BARI + RDV (n=515): 284/496 (57.3) | PBO + RDV (n=518): 285/498 (57.2) |
bPercentages are based on the number of subjects with data available for the individual comorbidity.
SELECT IMPORTANT SAFETY INFORMATION RELATED TO ABNORMAL LABORATORY VALUES
Evaluate estimated glomerular filtration rate (eGFR), liver enzymes, and complete blood count at baseline and thereafter according to local patient management practice. Monitor closely when treating patients with abnormal baseline and post-baseline laboratory values. Follow dose adjustments as recommended in the Fact Sheet for Healthcare Providers for patients with abnormal renal, hematological and hepatic laboratory values. Manage patients according to routine clinical guidelines.
Data Analyses
ACTT-2 Primary Endpoint and Subgroup Analyses - Recovery Outcomes
For the overall population, the median time to recovery (defined as discharged from hospital or hospitalized but not requiring supplemental oxygen or ongoing medical care) was 7 days for baricitinib and remdesivir compared to 8 days for placebo and remdesivir (p=0.047), HR: 1.15 (95% CI, 1.00 to 1.31).
ACTT-2: Recovery Outcomes in the ITT Population According to Baseline Ordinal Scale Score
4a Not requiring supplemental oxygen
Recoveries, n
BARI + RDV (n=70): 67
PBO + RDV (n=72): 69
Median time to recovery, days (95% CI)
BARI + RDV (n=70): 5 (4-6)
PBO + RDV (n=72): 4 (4-6)
HR (95% CI)
0.88 (0.63-1.23)
aUnder this Emergency Use Authorization, baricitinib, in combination with remdesivir, is not authorized for use in patients who do not require supplemental oxygen. The combination is only authorized for use in hospitalized patients requiring supplemental oxygen, invasive mechanical ventilation, or ECMO.1
5 Low-flow oxygen
Recoveries, n
BARI + RDV (n=288): 262
PBO + RDV (n=276): 243
Median time to recovery, days (95% CI)
BARI + RDV (n=288): 5 (5-6)
PBO + RDV (n=276): 6 (5-6)
HR (95% CI)
1.17 (0.98-1.39)
6 High-flow oxygen/NIMV
Recoveries, n
BARI + RDV (n=103): 82
PBO + RDV (n=113): 73
Median time to recovery, days (95% CI)
BARI + RDV (n=103): 10 (9-13)
PBO + RDV (n=113): 18 (13-21)
HR (95% CI)
1.51 (1.10-2.08)
7 Mechanical ventilation/ECMO
Recoveries, n
BARI + RDV (n=54): 22
PBO + RDV (n=57): 21
Median time to recovery, days (95% CI)
BARI + RDV (n=54): NE (25-NE)
PBO + RDV (n=57): NE (26-NE)
HR (95% CI)
1.08 (0.59-1.97)
| 4a Not requiring supplemental oxygen | 5 Low-flow oxygen | 6 High-flow oxygen/NIMV | 7 Mechanical ventilation/ECMO | |||||
|---|---|---|---|---|---|---|---|---|
| BARI + RDV (n=70) | PBO + RDV (n=72) | BARI + RDV (n=288) | PBO + RDV (n=276) | BARI + RDV (n=103) | PBO + RDV (n=113) | BARI + RDV (n=54) | PBO + RDV (n=57) | |
| Recoveries, n | 67 | 69 | 262 | 243 | 82 | 73 | 22 | 21 |
| Median time to recovery, days (95% CI) | 5 (4-6) | 4 (4-6) | 5 (5-6) | 6 (5-6) | 10 (9-13) | 18 (13-21) | NE (25-NE) | NE (26-NE) |
| HR (95% CI) | 0.88 (0.63-1.23) | 1.17 (0.98-1.39) | 1.51 (1.10-2.08) | 1.08 (0.59-1.97) | ||||
aUnder this Emergency Use Authorization, baricitinib, in combination with remdesivir, is not authorized for use in patients who do not require supplemental oxygen. The combination is only authorized for use in hospitalized patients requiring supplemental oxygen, invasive mechanical ventilation, or ECMO.1
Analyses by baseline ordinal scale score, while prespecified, were not adjusted for multiplicity and therefore cannot be used to conclude treatment effects within or between subgroups.
ACTT-2=Adaptive COVID-19 Treatment Trial 2; BARI=baricitinib; ECMO=extracorporeal membrane oxygenation; HR=hazard ratio; ITT=intent-to-treat; NE=not possible to estimate; NIMV=non-invasive mechanical ventilation; PBO=placebo; RR=rate ratio; RDV=remdesivir.
ACTT-2 Secondary Endpoint and Subgroup Analyses - Ordinal Scale Score on Day 15
"In the overall population, patients assigned to baricitinib and remdesivir were more likely to have a better clinical status (according to an 8-point ordinal scale) at Day 15 compared to patients assigned to placebo and remdesivir [odds ratio: 1.26 (95% CI 1.01, 1.57); p=0.044].
Ordinal Scale Score at Day 15 According to Baseline Score:
4a Not requiring supplemental oxygen
Day 15 Ordinal Scale Score - 1
BARI + RDV (n=70) n (%): 33 (47.1)
PBO + RDV (n=72) n (%): 44 (61.1)
Day 15 Ordinal Scale Score - 2
BARI + RDV (n=70) n (%): 25 (35.7)
PBO + RDV (n=72) n (%): 20 (27.8)
Day 15 Ordinal Scale Score - 3
BARI + RDV (n=70) n (%): 5 (7.1)
PBO + RDV (n=72) n (%): 2 (2.8)
Day 15 Ordinal Scale Score - 4
BARI + RDV (n=70) n (%): 7 (10.0)
PBO + RDV (n=72) n (%): 6 (8.3)
Day 15 Ordinal Scale Score - 5
BARI + RDV (n=70) n (%): 0 (0)
PBO + RDV (n=72) n (%): 0 (0)
Day 15 Ordinal Scale Score - 6
BARI + RDV (n=70) n (%): 0 (0)
PBO + RDV (n=72) n (%): 0 (0)
Day 15 Ordinal Scale Score - 7
BARI + RDV (n=70) n (%): 0 (0)
PBO + RDV (n=72) n (%): 0 (0)
Day 15 Ordinal Scale Score - 8
BARI + RDV (n=70) n (%): 0 (0)
PBO + RDV (n=72) n (%): 0 (0)
OR (95% CI)
0.6 (0.3-1.1)
aUnder this Emergency Use Authorization, baricitinib, in combination with remdesivir, is not authorized for use in patients who do not require supplemental oxygen. The combination is only authorized for use in hospitalized patients requiring supplemental oxygen, invasive mechanical ventilation, or ECMO.1
5 Low-flow oxygen
Day 15 Ordinal Scale Score - 1
BARI + RDV (n=288) n (%): 114 (39.6)
PBO + RDV (n=276) n (%): 101 (36.6)
Day 15 Ordinal Scale Score - 2
BARI + RDV (n=288) n (%): 120 (41.7)
PBO + RDV (n=276) n (%): 115 (41.7)
Day 15 Ordinal Scale Score - 3
BARI + RDV (n=288) n (%): 2 (0.7)
PBO + RDV (n=276) n (%): 1 (0.4)
Day 15 Ordinal Scale Score - 4
BARI + RDV (n=288) n (%): 14 (4.9)
PBO + RDV (n=276) n (%): 7 (2.5)
Day 15 Ordinal Scale Score - 5
BARI + RDV (n=288) n (%): 18 (6.2)
PBO + RDV (n=276) n (%): 27 (9.8)
Day 15 Ordinal Scale Score - 6
BARI + RDV (n=288) n (%): 9 (3.1)
PBO + RDV (n=276) n (%): 1 (0.4)
Day 15 Ordinal Scale Score - 7
BARI + RDV (n=288) n (%): 8 (2.8)
PBO + RDV (n=276) n (%): 19 (6.9)
Day 15 Ordinal Scale Score - 8
BARI + RDV (n=288) n (%): 3 (1.0)
PBO + RDV (n=276) n (%): 5 (1.8)
OR (95% CI)
1.2 (0.9-1.6)
6 High-flow oxygen/NIMV
Day 15 Ordinal Scale Score - 1
BARI + RDV (n=103) n (%): 27 (26.2)
PBO + RDV (n=113) n (%): 17 (15.0)
Day 15 Ordinal Scale Score - 2
BARI + RDV (n=103) n (%): 30 (29.1)
PBO + RDV (n=113) n (%): 24 (21.2)
Day 15 Ordinal Scale Score - 3
BARI + RDV (n=103) n (%): 0 (0)
PBO + RDV (n=113) n (%): 0 (0)
Day 15 Ordinal Scale Score - 4
BARI + RDV (n=103) n (%): 7 (6.8)
PBO + RDV (n=113) n (%): 3 (2.7)
Day 15 Ordinal Scale Score - 5
BARI + RDV (n=103) n (%): 15 (14.6)
PBO + RDV (n=113) n (%): 20 (17.7)
Day 15 Ordinal Scale Score - 6
BARI + RDV (n=103) n (%): 7 (6.8)
PBO + RDV (n=113) n (%): 16 (14.2)
Day 15 Ordinal Scale Score - 7
BARI + RDV (n=103) n (%): 15 (14.6)
PBO + RDV (n=113) n (%): 28 (24.8)
Day 15 Ordinal Scale Score - 8
BARI + RDV (n=103) n (%): 2 (1.9)
PBO + RDV (n=113) n (%): 5 (4.4)
OR (95% CI)
2.2 (1.4 -3.6)
7 Mechanical ventilation/ECMO
Day 15 Ordinal Scale Score - 1
BARI + RDV (n=54) n (%): 3 (5.6)
PBO + RDV (n=57) n (%): 3 (5.3)
Day 15 Ordinal Scale Score - 2
BARI + RDV (n=54) n (%): 2 (3.7)
PBO + RDV (n=57) n (%): 4 (7.0)
Day 15 Ordinal Scale Score - 3
BARI + RDV (n=54) n (%): 1 (1.9)
PBO + RDV (n=57) n (%): 0 (0)
Day 15 Ordinal Scale Score - 4
BARI + RDV (n=54) n (%): 3 (5.6)
PBO + RDV (n=57) n (%): 2 (3.5)
Day 15 Ordinal Scale Score - 5
BARI + RDV (n=54) n (%): 10 (18.5)
PBO + RDV (n=57) n (%): 3 (5.3)
Day 15 Ordinal Scale Score - 6
BARI + RDV (n=54) n (%): 4 (7.4)
PBO + RDV (n=57) n (%): 2 (3.5)
Day 15 Ordinal Scale Score - 7
BARI + RDV (n=54) n (%): 25 (46.3)
PBO + RDV (n=57) n (%): 36 (63.2)
Day 15 Ordinal Scale Score - 8
BARI + RDV (n=54) n (%): 6 (11.1)
PBO + RDV (n=57) n (%): 7 (12.3)
OR (95% CI)
1.7 (0.8 – 3.4)
| 4a Not requiring supplemental oxygen | 5 Low-flow oxygen | 6 High-flow oxygen/NIMV | 7 Mechanical ventilation/ECMO | |||||
|---|---|---|---|---|---|---|---|---|
| Ordinal scale score at Day 15 | BARI + RDV (n=70) n (%) | PBO + RDV (n=72) n (%) | BARI + RDV (n=288) n (%) | PBO + RDV (n=276) n (%) | BARI + RDV (n=103) n (%) | PBO + RDV (n=113) n (%) | BARI + RDV (n=54) n (%) | PBO + RDV (n=57) n (%) |
| Ordinal scale score at Day 15: 1 | 33 (47.1) | 44 (61.1) | 114 (39.6) | 101 (36.6) | 27 (26.2) | 17 (15.0) | 3 (5.6) | 3 (5.3) |
| Ordinal scale score at Day 15: 2 | 25 (35.7) | 20 (27.8) | 120 (41.7) | 115 (41.7) | 30 (29.1) | 24 (21.2) | 2 (3.7) | 4 (7.0) |
| Ordinal scale score at Day 15: 3 | 5 (7.1) | 2 (2.8) | 2 (0.7) | 1 (0.4) | 0 (0) | 0 (0) | 1 (1.9) | 0 (0) |
| Ordinal scale score at Day 15: 4 | 7 (10.0) | 6 (8.3) | 14 (4.9) | 7 (2.5) | 7 (6.8) | 3 (2.7) | 3 (5.6) | 2 (3.5) |
| Ordinal scale score at Day 15: 5 | 0 (0) | 0 (0) | 18 (6.2) | 27 (9.8) | 15 (14.6) | 20 (17.7) | 10 (18.5) | 3 (5.3) |
| Ordinal scale score at Day 15: 6 | 0 (0) | 0 (0) | 9 (3.1) | 1 (0.4) | 7 (6.8) | 16 (14.2) | 4 (7.4) | 2 (3.5) |
| Ordinal scale score at Day 15: 7 | 0 (0) | 0 (0) | 8 (2.8) | 19 (6.9) | 15 (14.6) | 28 (24.8) | 25 (46.3) | 36 (63.2) |
| Ordinal scale score at Day 15: 8 | 0 (0) | 0 (0) | 3 (1.0) | 5 (1.8) | 2 (1.9) | 5 (4.4) | 6 (11.1) | 7 (12.3) |
| OR (95% CI) | 0.6 (0.3-1.1) | 1.2 (0.9-1.6) | 2.2 (1.4 -3.6) | 1.7 (0.8 – 3.4) | ||||
aUnder this Emergency Use Authorization, baricitinib, in combination with remdesivir, is not authorized for use in patients who do not require supplemental oxygen. The combination is only authorized for use in hospitalized patients requiring supplemental oxygen, invasive mechanical ventilation, or ECMO.1
Analyses by baseline ordinal scale score, while prespecified, were not adjusted for multiplicity and therefore cannot be used to conclude treatment effects within or between subgroups.
The ordinal score at Day 15 (±2 days visit window) is the patient’s worst score on the ordinal scale during the previous day.
In the overall population, the proportion of patients who progressed to noninvasive ventilation/high-flow oxygen or invasive mechanical ventilation or died by Day 29 was lower in baricitinib and remdesivir (23%) compared to placebo and remdesivir (28%) odds ratio: 0.74 (95% CI 0.56, 0.99); p=0.039]. Patients who required noninvasive ventilation/high-flow oxygen or invasive mechanical ventilation (including ECMO) at baseline needed to worsen by at least 1 point on an 8-point ordinal scale to progress.
ACTT-2=Adaptive COVID-19 Treatment Trial 2; BARI=baricitinib; ECMO=extracorporeal membrane oxygenation; NIMV=non-invasive mechanical ventilation; OR=odds ratio; PBO=placebo; RDV=remdesivir.
ACTT-2 Secondary Endpoint and Subgroup Analyses - Mortality
In the overall population, the proportion of patients who died by Day 29 was 4.7% (24/515) for baricitinib and remdesivir vs 7.1% (37/518) for placebo and remdesivir [Kaplan-Meier estimated difference in Day 29 probability of mortality: -2.6% (95% CI -5.8%, 0.5%)].
Mortality According to Baseline Ordinal Scale Score:
4a Not requiring supplemental oxygen
Mortality over first 14 daysb
HR (95% CI)
NE
No. of deaths
BARI + RDV (n=70): 0
PBO + RDV (n=72): 0
Kaplan-Meier estimate of mortality, % (95% CI)
BARI + RDV (n=70): 0 (NE-NE)
PBO + RDV (n=72): 0 (NE-NE)
Mortality over 28 daysb
HR (95% CI)
NE
No. of deaths
BARI + RDV (n=70): 0
PBO + RDV (n=72): 0
Kaplan-Meier estimate of mortality, % (95% CI)
BARI + RDV (n=70): 0 (NE-NE)
PBO + RDV (n=72): 0 (NE-NE)
aUnder this Emergency Use Authorization, baricitinib, in combination with remdesivir, is not authorized for use in patients who do not require supplemental oxygen. The combination is only authorized for use in hospitalized patients requiring supplemental oxygen, invasive mechanical ventilation, or ECMO.1
bDays post-randomization noted as “over first 14 days/over 28 days” correspond to study Days 15 and 29, respectively.
5 Low-flow oxygen
Mortality over first 14 daysb
HR (95% CI)
0.73 (0.16-3.26)
No. of deaths
BARI + RDV (n=288): 3
PBO + RDV (n=276): 4
Kaplan-Meier estimate of mortality, % (95% CI)
BARI + RDV (n=288): 1.1 (0.4-3.4)
PBO + RDV (n=276): 1.5 (0.6-3.9)
Mortality over 28 daysb
HR (95% CI)
0.40 (0.14-1.14)
No. of deaths
BARI + RDV (n=288): 5
PBO + RDV (n=276): 12
Kaplan-Meier estimate of mortality, % (95% CI)
BARI + RDV (n=288): 1.9 (0.8-4.4)
PBO + RDV (n=276): 4.7 (2.7-8.1)
bDays post-randomization noted as “over first 14 days/over 28 days” correspond to study Days 15 and 29, respectively.
6 High-flow oxygen/NIMV
Mortality over first 14 daysb
HR (95% CI)
0.21 (0.02-1.80)
No. of deaths
BARI + RDV (n=103): 1
PBO + RDV (n=113): 5
Kaplan-Meier estimate of mortality, % (95% CI)
BARI + RDV (n=103): 1.0 (0.1-6.7)
PBO + RDV (n=113): 4.6 (2.0-10.8)
Mortality over 28 daysb
HR (95% CI)
0.55 (0.22-1.38)
No. of deaths
BARI + RDV (n=103): 7
PBO + RDV (n=113): 13
Kaplan-Meier estimate of mortality, % (95% CI)
BARI + RDV (n=103): 7.5 (3.6-15.2)
PBO + RDV (n=113): 12.9 (7.7-21.3)
bDays post-randomization noted as “over first 14 days/over 28 days” correspond to study Days 15 and 29, respectively.
7 Mechanical ventilation/ECMO
Mortality over first 14 daysb
HR (95% CI)
0.69 (0.19-2.44)
No. of deaths
BARI + RDV (n=54): 4
PBO + RDV (n=57): 6
Kaplan-Meier estimate of mortality, % (95% CI)
BARI + RDV (n=54): 7.6 (2.9-19.1)
PBO + RDV (n=57): 11.3 (5.3-23.5)
Mortality over 28 daysb
HR (95% CI)
1.00 (0.45-2.22)
No. of deaths
BARI + RDV (n=54): 12
PBO + RDV (n=57): 12
Kaplan-Meier estimate of mortality, % (95% CI)
BARI + RDV (n=54): 23.1 (13.8-37.1)
PBO + RDV (n=57): 22.6 (13.5-36.4)
bDays post-randomization noted as “over first 14 days/over 28 days” correspond to study Days 15 and 29, respectively.
| 4a Not requiring supplemental oxygen | 5 Low-flow oxygen | 6 High-flow oxygen/NIMV | 7 Mechanical ventilation/ECMO | |||||
|---|---|---|---|---|---|---|---|---|
| BARI + RDV (n=70) | PBO + RDV (n=72) | BARI + RDV (n=288) | PBO + RDV (n=276) | BARI + RDV (n=103) | PBO + RDV (n=113) | BARI + RDV (n=54) | PBO + RDV (n=57) | |
| Mortality over first 14 daysb | ||||||||
| HR (95% CI) | NE | 0.73 (0.16-3.26) | 0.21 (0.02-1.80) | 0.69 (0.19-2.44) | ||||
| No. of deaths | 0 | 0 | 3 | 4 | 1 | 5 | 4 | 6 |
| Kaplan-Meier estimate of mortality, % (95% CI) | 0 (NE-NE) | 0 (NE-NE) | 1.1 (0.4-3.4) | 1.5 (0.6-3.9) | 1.0 (0.1-6.7) | 4.6 (2.0-10.8) | 7.6 (2.9-19.1) | 11.3 (5.3-23.5) |
| Mortality over 28 daysb | ||||||||
| HR (95% CI) | NE | 0.40 (0.14-1.14) | 0.55 (0.22-1.38) | 1.00 (0.45-2.22) | ||||
| No. of deaths | 0 | 0 | 5 | 12 | 7 | 13 | 12 | 12 |
| Kaplan-Meier estimate of mortality, % (95% CI) | 0 (NE-NE) | 0 (NE-NE) | 1.9 (0.8-4.4) | 4.7 (2.7-8.1) | 7.5 (3.6-15.2) | 12.9 (7.7-21.3) | 23.1 (13.8-37.1) | 22.6 (13.5-36.4) |
aUnder this Emergency Use Authorization, baricitinib, in combination with remdesivir, is not authorized for use in patients who do not require supplemental oxygen. The combination is only authorized for use in hospitalized patients requiring supplemental oxygen, invasive mechanical ventilation, or ECMO.1
bDays post-randomization noted as “over first 14 days/over 28 days” correspond to study Days 15 and 29, respectively.
Analyses by baseline ordinal scale score, while prespecified, were not adjusted for multiplicity and therefore cannot be used to conclude treatment effects within or between subgroups.
ACTT-2=Adaptive COVID-19 Treatment Trial 2; BARI=baricitinib; ECMO=extracorporeal membrane oxygenation; HR=hazard ratio; NE=not possible to estimate; NIMV=non-invasive mechanical ventilation; PBO=placebo; RDV=remdesivir.
Adverse Events
Comparisons and Confidence Intervals for Adverse Events in the As-Treated Populationa
| Patients with at least 1 | Placebo + remdesivir (N=509) n (%) | Baricitinib + remdesivir (N=507) n (%) | Risk difference % (95% CI) |
|---|---|---|---|
| Patients with at least 1: AE | Placebo + remdesivir (N=509) n (%): 242 (48) | Baricitinib + remdesivir (N=507) n (%): 210 (41) | Risk difference, % (95% CI): -6 (-12, 0) |
| Patients with at least 1: Grade 3-4 AE | Placebo + remdesivir (N=509) n (%): 238 (47) | Baricitinib + remdesivir (N=507) n (%): 207 (41) | Risk difference, % (95% CI): -6 (-12, 0) |
| Patients with at least 1: SAE | Placebo + remdesivir (N=509) n (%): 103 (20) | Baricitinib + remdesivir (N=507) n (%): 77 (15) | Risk difference, % (95% CI): -5 (-10, 0) |
| Patients with at least 1: SAE with fatal outcome | Placebo + remdesivir (N=509) n (%): 31 (6) | Baricitinib + remdesivir (N=507) n (%): 19 (4) | Risk difference, % (95% CI): -2 (-5, 0) |
| Patients with at least 1: AE leading to discontinuation of study drug | Placebo + remdesivir (N=509) n (%): 59 (12) | Baricitinib + remdesivir (N=507) n (%): 34 (7) | Risk difference, % (95% CI): -5 (-8, -1) |
| Patients with at least 1: Infections | Placebo + remdesivir (N=509) n (%): 50 (10) | Baricitinib + remdesivir (N=507) n (%): 32 (6) | Risk difference, % (95% CI): -4 ( -7, 0) |
| Patients with at least 1: VTE | Placebo + remdesivir (N=509) n (%): 16 (3) | Baricitinib + remdesivir (N=507) n (%): 21 (4) | Risk difference, % (95% CI): 1 (-1, 3) |
| Patients with at least 1: Pulmonary Embolism | Placebo + remdesivir (N=509) n (%): 2 (0.4) | Baricitinib + remdesivir (N=507) n (%): 5 (1) | Risk difference, % (95% CI): 0.6 (-0.4, 1.6) |
aPatients are counted for each category regardless of the number of events.
AE=adverse event; CI=confidence interval; N=number of patients in the as-treated population; n=number of patients reporting at least 1 event; SAE=serious adverse event; VTE=venous thromboembolic events.