Trial NCT04311697
Publication Youssef J, SSRN, 2021 (preprint)
Dates: 2020-05-15 to 2020-12-24
Funding: Mixed (NeuroRx, Inc. and Relief Therapeutics, AG)
Conflict of interest: Yes
| Methods | |
| RCT Blinding: double blinding | |
| Location :
Multicenter / USA Follow-up duration (days): 60 | |
| Inclusion criteria | Respiratory failure by FDA definition of requiring High Flow Nasal Cannula >20L, noninvasive ventilation, or mechanical ventilation, PCR+ test for Covid-19, and less than seven days since onset of respiratory failure |
| Exclusion criteria | Pregnancy; Mechanical ventilation for more than 7 days in primary cohort; Mechanical ventilation>21 days in the exploratory cohort; Mean Arterial Pressure < 65 mm Hg with use of pressor per ICU protocol; Irreversible condition (other than COVID-19) with projected fatal course; ECMO; Current or recent (within 30 d) enrollment in another investigational trial of anti-IL6 drug; Active diagnosis of Acquired immune deficiency syndrome; Transplant patients currently immunosuppressed; Chemotherapy-induced neutropenia (granulocyte count <1000/mm3); Cardiogenic shock; congestive heart failure - NYHA Class 3 or 4; Recent myocardial infarction - within last 6 months and troponin > 0.5 Anuria (urine output < 50 ml/d) or other signs of multi-organ failure Severe liver disease with portal hypertension; Recent stroke or head trauma within last 12 months; Increased intracranial pressure, or other serious neurologic disorder; |
| Interventions | |
| Treatment
Aviptadil Three 12-hour intravenous infusions over 3 days at graduating doses of 50, 100, and 150 pmol/kg/hr. |
|
| Control
Placebo | |
| Participants | |
| Randomized 203 participants (n1=136 / n2= 67) | |
| Characteristics of participants N=203 Mean age : 61 135 males Severity : Mild: n=0 / Moderate: n=0/ Severe: n=* Critical: n=* | |
| Primary outcome | |
| In the register Resolution of Respiratory Failure (Composite Endpoint) [ Time Frame: Day 0 through day 28 (interim) and 60 ] Cumulative distribution of the time to respiratory failure resolution (without relapse over 7 days) with concurrent survival through day 28 | |
| In the report Alive at day 60 and free of respiratory failure | |
| Documents available |
Protocol NR Statistical plan NR Data-sharing stated Unclear |
| Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Some concerns |
| General comment |
In addition to the pre-print articles, the study registry was used in data extraction and risk of bias assessment. The study achieved the target sample size specified in the trial registry. There is no change from the trial registration in the intervention and control treatments. The primary and secondary outcomes in the prospective versions of the registry do not reflect those reported in the paper. However, the study highlights that day 60 outcomes were added retrospectively, since patients were still in ICU after 28 days of follow-up. Further, adverse events were added following the recommendation of the DSMB. Baseline severity of patients by proportion per arm were not reported.
On 25th of May, 2021, this study was updated based on the pre-print of the final follow-up. |