Primary outcomeCount of participants· Day 28
Resolution of Respiratory Failure (Alive and Free of Respiratory Failure)
| Group | Value (Participants) |
|---|---|
| Aviptadil IV in Escalating Doses + Standard of Care | 72 |
| Placebo + Standard of Care | 33 |
Trial · Interventional
CompletedPhase 2/3Results postedRegistry dataIntravenous Aviptadil for Critical COVID-19 With Respiratory Failure
Short name COVID-AIV
NCTNCT04311697 (opens ClinicalTrials.gov in a new tab)Other idCOVID-AIV
Overview
- Status
- Completed
- Phase
- Phase 2/3
- Enrollment
- 203 participants (actual)
- Sponsor
- APR Applied Pharma Research s.a. · Other
- Design
- Randomized · Quadruple masking
- Countries
1 country
United States
- Start
- 15 May 2020
- Primary completion
- 22 Feb 2021
- Completion
- 22 Feb 2021
- First posted
- 17 Mar 2020
- Last update posted
- 24 Jul 2023
- Conditions
- Critical COVID-19 With Respiratory Failure · Acute Respiratory Distress Syndrome (ARDS) · Corona Virus Infection · Acute Lung Injury
Timeline
1 trial · 1 completed · 1 with posted results
- Completed
- Ongoing
- Not yet recruiting
- Stopped
- Estimated dates (est.)
- Results posted
202020212022
- Ph 2/3
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
Novel Corona Virus (SARS-CoV-2) is known to cause Respiratory Failure, which is the hallmark of Acute COVID-19, as defined by the new NIH/FDA classification. Approximately 50% of those who develop Critical COVID-19 die, despite intensive care and mechanical ventilation. Patients with Critical COVID-19 and respiratory failure, currently treated with high flow nasal oxygen, non-invasive ventilation or mechanical ventilation will be treated with ZYESAMI (aviptadil), a synthetic form of Human Vasoactive Intestinal Polypeptide (VIP) plus maximal intensive care vs. placebo + maximal intensive care. Patients will be randomized to intravenous Aviptadil will receive escalating doses from 50 -150 pmol/kg/hr over 12 hours.
Interventions
- Aviptadil by intravenous infusion + standard of careDrug
- Normal Saline Infusion + standard of careDrug
Arms2
Experimental
Aviptadil IV in escalating doses + standard of care
Patients will be administered Aviptadil IV in escalating doses of 50 pmol, 100 pmol, 150 pmol/kg/hr
Experimental
Placebo + standard of care
Patients will first be treated with placebo infusion + maximal intensive care
Primary outcomes1
Outcomes the sponsor listed as primary.
Resolution of Respiratory Failure (Alive and Free of Respiratory Failure)
Time frame · Day 28
Registry description
Participant is Alive and Free of Respiratory Failure (without subsequent relapse over 7 days) determined as no longer requiring acute care or more than low flow oxygen
Secondary outcomes(3)
Number of Participants Alive at Day 60
Time frame · Day 60
Registry description
Survival probability on logistic regression through day 60
Number of Participants Achieving a Score of 6-8 on NIAID Ordinal Score Through Day 60
Time frame · Day 60
Registry description
Achievement of score 6-8 on NIAID Ordinal Scale through day 60 The NIAID score is the patient's status on the following 8-point scale:1)Death2)Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO),3)Hospitalized, on non-invasive ventilation or high flow oxygen devices4)Hospitalized, requiring supplemental oxygen5)Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)6)Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care7)Not hospitalized, limitation on activities and/or requiring home oxygen8)Not hospitalized, no limitations on activities-- a lower NIAID score is a worse outcome.
Oxygenation Index as Measured by PaO2:FiO2 Ratio
Time frame · Day 7
Registry description
oxygenation index (also known as Respiratory Distress Ratio) as measured by PaO2:FiO2 ratio (Respiratory Distress while on mechanical ventilation). RDR: PaO2:FiO2 represents an intermediate clinical endpoint that is known to be predictive of survival. RDR can only be measured in patients on mechanical ventilation because of its reliance on arterial blood gas measurements that are not routinely collected in non-intubated patients. A higher score indicates a better clinical outcome.
Posted results
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
Primary outcome results
Secondary and other outcome results(4)
Secondary outcomeCount of participants· Day 60
Number of Participants Alive at Day 60
| Group | Value (Participants) |
|---|---|
| Aviptadil IV in Escalating Doses + Standard of Care | 85 |
| Placebo + Standard of Care | 35 |
Secondary outcomeCount of participants· Day 60
Number of Participants Achieving a Score of 6-8 on NIAID Ordinal Score Through Day 60
| Group | Value (Participants) |
|---|---|
| Aviptadil IV in Escalating Doses + Standard of Care | 76 |
| Placebo + Standard of Care | 35 |
Secondary outcomeMean· Day 7
Oxygenation Index as Measured by PaO2:FiO2 Ratio
| Group | Value (PaO2:FiO2 ratio) | Spread |
|---|---|---|
| Aviptadil IV in Escalating Doses + Standard of Care | 139.2 | 77.0 |
| Placebo + Standard of Care | 116.2 | 41.77 |
Other pre specified outcomeMean· Day 28
Change in IL-6
| Group | Value (IL-6 picogram/mL) | Spread |
|---|---|---|
| Aviptadil IV in Escalating Doses + Standard of Care | 19.8 | 39.9 |
| Placebo + Standard of Care | 23.5 | 39.7 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Aviptadil IV in Escalating Doses + Standard of CarePatients will be administered Aviptadil IV in escalating doses of 50 pmol, 100 pmol, 150 pmol/kg/hr Aviptadil by intravenous infusion + standard of care: Aviptadil by intravenous infusion + standard of care (SOC). SOC is defined not to include extracorporeal mechanical oxygenation. Those requiring ECMO will be withdrawn from the study as treatment failures. | 46 / 131 | 58 / 131 | 102 / 131 |
| Placebo + Standard of CarePatients will first be treated with placebo infusion + maximal intensive care Normal Saline Infusion + standard of care: Saline by intravenous infusion + standard of care (SOC). SOC is defined not to include extracorporeal mechanical oxygenation. Those requiring ECMO will be withdrawn from the study as treatment failures. | 30 / 65 | 32 / 65 | 49 / 65 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies1
Studies that cite this trial.
Studies with results
1 study on this page
Indexing hint: Randomized controlled trial · 2022
7 results
The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial.
Youssef et al. 2022Critical care medicinecited by 19
PMID 36044317PMC9555831DOI 10.1097/ccm.0000000000005660PUB-36044317
Free to read · publisher termsCC BY-NC-ND7 results
Eligibility
Who could join, as posted.
- Sex
- All
- Age
- from 18 Years up to 100 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria:
* Critical COVID-19 with respiratory failure
* Physician determination that patient is on maximal conventional medical therapy
Exclusion Criteria:
1. Pregnancy (pregnant women may apply for open label treatment under compassionate care IND
2. Age \<18 years
3. Mechanical ventilation for more than 7 days in primary cohort. Mechanical ventilation\>21 days in the exploratory cohort
4. Mean Arterial Pressure \< 65 mm Hg with use of pressor per ICU protocol
5. Irreversible condition (other than COVID-19) with projected fatal course
6. ECMO
7. Current or recent (within 30 d) enrollment in another investigational trial of anti-IL6 drug;
8. Active diagnosis of Acquired immune deficiency syndrome;
9. Transplant patients currently immunosuppressed;
10. Chemotherapy-induced neutropenia (granulocyte count \<1000/mm3);
11. Cardiogenic shock; congestive heart failure - NYHA Class 3 or 4;
12. Recent myocardial infarction - within last 6 months and troponin \> 0.5
13. Anuria (urine output \< 50 ml/d) or other signs of multi-organ failure
14. Severe liver disease with portal hypertension;
15. Recent stroke or head trauma within last 12 months
16. Increased intracranial pressure, or other serious neurologic disorder;
17. Liquid Diarrhea more than 3x/day; defined as more than 3 non-bloody watery stools within a 24-hour period, requiring additional fluid and electrolyte supplementation
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