Table 3.
Safety Outcomes for the Aviptadil versus Placebo Comparison: Modified Intention to Treat Cohort
| Outcomes | Aviptadil (n=231), n (%) | Placebo (n=230), n (%) | Odds or Hazard Ratio for Aviptadil/Placebo (95% CI) | p value |
|---|---|---|---|---|
| Infusion reactions of any grade, Days 0–2 a | ||||
| Any reaction | 200 (86.6) | 132 (57.4) | -- | <0.001 |
| Facial flushing | 34 (14.7) | 14 (6.1) | -- | 0.002 |
| Diarrhea | 92 (39.8) | 26 (11.3) | -- | <0.001 |
| Tachycardia | 22 (9.5) | 11 (4.8) | -- | 0.049 |
| Hypotension | 135 (58.4) | 95 (41.3) | -- | <0.001 |
| Infusion adjustments due to AEb, Days 0–2 | ||||
| Pause | 71 (30.7) | 35 (15.2) | -- | |
| Reduction in rate | 53 (22.9) | 20 (8.7) | -- | |
| Discontinuation | 24 (10.4) | 13 (5.7) | ||
| Safety through Day 5 c | ||||
| Composite safety outcome of SAE, Grade 3/4 AE, Organ Failure/Serious Infection, or Death | 146 (63.2) | 129 (56.1) | 1. | 0.10 |
| Select components | ||||
| Deathc | 13 (5.6) | 11 (4.8) | 1.19 (0.52, 2.71) | 0.68 |
| Hypotension or shockc,d | 69 (29.9) | 64 (27.8) | 0.62 | |
| Diarrheac,e | 4 (1.7) | 2 (0.9) | 0.42 | |
| Cardiacc,f | 24 (10.4) | 22 (9.6) | -- | 0.76 |
| Renalc,g | 20 (9.4) | 12 (5.4) | -- | 0.10 |
| Barotraumac,h | 5 (2.2) | 1 (0.4) | 0.14 | |
| Safety through Day 28 i | ||||
| Composite safety outcome of SAE, Grade 3/4 AE, Organ Failure/Serious Infection, or Death | 181 (78.4) | 172 (74.8) | 1.17 (0.95,1.44) | 0.15 |
| Select components | ||||
| Deathi | 69 (29.9) | 66 (28.7) | 1.05 (0.75, 1.47) | 0.77 |
| Hypotension or shockd,i | 112 (48.5) | 114 (49.6) | -- | 0.82 |
| Diarrheae,i | 7 (3.0) | 4 (1.7) | -- | 0.37 |
| Cardiac f,i | 56 (24.2) | 49 (21.3) | -- | 0.49 |
| Renalg,i | 41 (19.2) | 40 (17.9) | 0.56 | |
| Barotrauma h,i | 11 (4.8) | 14 (6.1) | 0.55 |
SAE=serious adverse event; AE=adverse event; MedDRA=Medical Dictionary for Regulatory Activities; SOC=System Organ Class.
P-value for comparing infusion reactions between treatment groups from Cochran-Mantel-Haenszel tests, stratified by disease severity at baseline.
Infusion adjustments are not mutually exclusive, see Table S17 for mutually exclusive representation.
Odds ratio for experiencing the event, aviptadil vs. placebo. Logistic regression model with 1 indicator for treatment group, stratified by disease severity at baseline. P-values for treatment group comparisons for select components from separate similar logistic regression models.
Any grade 3/4 hypotension during infusion, any organ failure report of hypotension with vasopressor use, any grade 3/4 AE, SAE, or death with MedDRA PT for hypotension, shock, shock haemorrhagic, distributive shock
Any grade 3/4 AE report if diarrhea. Per protocol, infusion-related diarrhea events excluded unless event led to discontinuation of blinded aviptadil.
Any grade 3/4 AE, SAE, or death with MedDRA Cardiac SOC, and any organ failure report of myocardial infarction, congestive heart failure III/IV, or atrial/ventricular tachyarrhythmia
Any grade 3/4 AE, SAE, or death with MedDRA PT for acute kidney injury, and organ failure report of new renal replacement therapy. Limited to patients without dialysis at baseline, Aviptadil= 213 and Placebo= 223
Any grade 3/4 AE, SAE, or death with MedDRA PT for pneumomediastinum or pneumothorax.
Hazard ratio for time to first event, aviptadil vs. placebo. Cox proportional hazards regression model with 1 indicator for treatment group stratified by disease severity. P-values for treatment group comparisons for select components from separate similar logistic regression models.