| Autor: |
Park Dj, Fernandez Jp, Jonathan C. Javitt, J.G. Youssef, Lavin P, Jayaweera D, Morganroth M, Lenhardt R, Lee R |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
SSRN Electronic Journal. |
| ISSN: |
1556-5068 |
| DOI: |
10.2139/ssrn.3830051 |
| Popis: |
Background: Respiratory failure is a lethal complication of COVID-19 that has remained resistant to drug therapy. Vasoactive Intestinal Peptide (VIP) has been granted Emergency Use Authorization and or Compassionate Care Authorization in multiple countries and is shown to upregulate surfactant production, inhibit cytokine synthesis, prevent cytopathy, and blocks replication of the SARS-CoV-2 virus in pulmonary cells. The aim of this study is to determine whether aviptadil (synthetic VIP) can improve survival and recovery in patients with COVID-19 respiratory failure compared to placebo. Methods: A multicenter, placebo-controlled trial in 196 patients with COVID-19 respiratory failure randomized 2:1 to receive 3 days of intravenous aviptadil (synthetic VIP) or placebo. The primary endpoint was “alive and free from respiratory failure at day 60.” We additionally studied the mechanistic effect of aviptadil on blocking cytokine production and its linkage to survival and recovery from respiratory failure. Analysis was by modified intent to treat using a prespecified regression model. Findings: When controlling for baseline severity and site of care, patients treated with aviptadil were significantly more likely to be alive and free from respiratory failure at 60 days, compared to those treated with placebo (P=.02) and demonstrated significance on numerous other clinical endpoints. Without controlling for site of care, a two-fold increased odds of survival was seen at 60 days (95% CI 1.0 – 3.9; P=.035). Biomarker analysis demonstrates that aviptadil significantly decreased the probability of an IL-6 increase relative to placebo (50% vs. 71%; p=.04) and that preventing this cytokine rise was highly correlated with survival and recovery (P |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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