Table 1.
Baseline Characteristics: Modified Intention to Treat Cohort for Aviptadil versus Placebo Comparison.
| Characteristic | Aviptadil n=231 | Aviptadil Placebo n=230 | Total N=461 |
|---|---|---|---|
|
Agent randomization/eligibility stratum, n(%)
Factorial (both agents) |
39 (16.9) |
46 (20.0) |
85 (18.4) |
| Aviptadil only, remdesivir contraindicated | 12 (5.2) | 10 (4.3) | 22 (4.8) |
| Aviptadil only, current/prior remdesivir use | 180 (77.9) | 174 (75.7) | 354 (76.8) |
| Age in years, median (IQR) | 58 (46, 67) | 57 (46, 66) | 57 (46, 66) |
| Female sex, n (%) | 94 (40.7) | 84 (36.5) | 178 (38.6) |
|
Race/ethnicity, n (%)
White |
102 (44.2) |
113 (49.1) |
215 (46.6) |
| Black | 40 (17.3) | 33 (14.3) | 73 (15.8) |
| Hispanic | 62 (26.8) | 57 (24.8) | 119 (25.8) |
| Asian | 7 (3.0) | 10 (4.3) | 17 (3.7) |
| Other | 20 (8.7) | 17 (7.4) | 37 (8.0) |
|
Body mass index in kg/m2, n (%)
30–39.9 |
92 (40.4) |
89 (39.0) |
181 (39.7) |
| ≥40.0 | 55 (24.1) | 61 (26.8) | 116 (25.4) |
| Days since onset of respiratory failure, median (IQR) | 2 (2, 3) | 2 (2, 3) | 2 (2, 3) |
|
Baseline respiratory support, n (%) HFNO device |
127 (55.0) |
118 (51.3) |
245 (53.1) |
| NIV | 9 (3.9) | 17 (7.4) | 26 (5.6) |
| IMV | 93 (40.3) | 92 (40.0) | 185 (40.1) |
| ECMO | 2 (0.9) | 3 (1.3) | 5 (1.1) |
| SF ratio (SPO2/FiO2) at randomization, median (IQR) | 134 (100, 176) | 131 (98, 186) | 133 (99, 182) |
| Estimated PF ratio (PaO2/FiO2) at randomizationa, median (IQR) | 83 (43, 133) | 79 (40, 145) | 74 (64, 86) |
| Bilateral lung infiltrates and SF ratio < 315, n (%) | 224 (97.4) | 221 (96.1) | 445 (96.7) |
| ARDS by Berlin criteriab, n (%) | 89 (38.7) | 90 (39.1) | 179 (38.9) |
| Vasopressor use at randomization, n (%) | 35 (15.2) | 29 (12.6) | 64 (13.9) |
|
Co-existing chronic illnessc n (%) Hypertension |
99 (42.9) |
92 (40.0) |
191 (41.4) |
| Diabetes mellitus | 82 (35.5) | 71 (30.9) | 153 (33.2) |
| Renal impairment | 45 (19.5) | 38 (16.5) | 83 (18.0) |
| Heart failure | 24 (10.4) | 15 (6.5) | 39 (8.5) |
| Immunocompromisedd n (%) | 36 (15.6) | 32 (13.9) | 68 (14.8) |
|
SARS-CoV-2 Vaccination Statuse, n (%)
No vaccine dose received Medication use prior to randomization, n% |
149 (64.5) |
151 (65.7) |
300 (65.1) |
| Remdesivir | 177 (76.6) | 172 (74.8) | 349 (75.7) |
| Corticosteroid | 219 (94.8) | 221 (96.1) | 440 (95.4) |
| Immunomodulator | 78 (33.8) | 78 (33.9) | 157 (33.9) |
|
Infecting variant (among the N=414 with positive nucleocapsid RT-PCRf), n (%)
Delta |
155 (74.9) |
150 (72.5) |
305 (73.7) |
| Omicron | 25 (12.1) | 25 (12.1) | 50 (12.1) |
| Other | 27 (13.0) | 32 (15.5) | 59 (14.3) |
| Genscript neutralising anti-spike antibody positiveg, n (%) | 157 (70.7) | 156 (70.0) | 313 (70.3) |
| BioRad anti-nucleocapsid antibody positiveh, n (%) | 171 (77.0) | 182 (81.6) | 355 (79.3) |
| Nucleocapsid antigen concentration (pg/mL)I, median (IQR) | 1246 (95, 6114) | 1502 (224, 6406) | 1294 (150, 6200) |
| Positive (concentration ≥3 pg/mL), n (%) | 211 (95.0) | 211 (94.6) | 422 (94.8) |
Abbreviations:HFNO, high flow nasal oxygen; NIV, non-invasive ventilation; IMV, invasive mechanical ventilation; ECMO; extracorporeal membrane oxygenation; IQR, interquartile range; n, number; kg, kilogram; m, meter; Covid-19, coronavirus disease 2019; RT-PCR, reverse transcription-polymerase chain reaction
Estimated PF ratio computed as PF ratio = (SF ratio – 64)/0.84. Rice TW, Wheeler AP, Bernard GR, et al. Comparison of the SpO2/FIO2 ratio and the PaO2/FIO2 ratio in patients with acute lung injury or ARDS. Chest. 2007 Aug;132(2):410–7. doi: 10.1378/chest.07-0617. Epub 2007 Jun 15. PMID: 17573487.
Bilateral lung infiltrates and PF ratio < 300 and (IMV or ECMO) at baseline.
Full list of co-existing chronic illness in the Supplementary Appendix (Table S6)
Immunocompromised defined as receiving antirejection medications, biologic medications to treat autoimmune disease or cancer, human immunodeficiency virus, or other immunosupmpressive condition
Not vaccinated = No known vaccine doses received before randomization (includes 18 with unknown vaccination status; 6 aviptadil, 12 placebo)
SARS-CoV-2 Delta variant was determined from a mid-turbinate swab at baseline based on RT-PCR detection of the N-terminal domain of the Delta spike. Omicron variant was determined by similar method. Data available for 414; 207 aviptadil and 207 placebo.
GenScript cPass surrogate SARS-CoV-2 neutralization assay (anti-spike); positive: ≥30% binding inhibition. Data available for 445; 222 aviptadil, 223 placebo.
BioRad Platelia anti-nucleocapsid assay (total antibody); positive: ≥1.0 sample/cutoff ratio. Data available for 445; 222 aviptadil, 223 placebo.
Quanterix Simoa nucleocapsid antigen; positive: ≥3 pg/mL. Data available for 445; 222 aviptadil, 223 placebo.