Aviptadil Therapy in Acute Respiratory Distress Syndrome Patients: A Systematic Review and Meta-analysis

Aim and background:Acute respiratory distress syndrome (ARDS) is a life-threatening condition with a high mortality rate despite advances in supportive care. Aviptadil, a synthetic analogue of vasoactive intestinal peptide (VIP), exhibits anti-inflammatory potential and cytoprotective effects that may improve pulmonary function. However, its role in improving survival among ARDS patients remains uncertain. This systematic review and meta-analysis aimed to evaluate the effectiveness of aviptadil in improving survival and oxygenation outcomes in ARDS. Methodology: A comprehensive search was conducted across six databases—PubMed, Scopus, Embase, Google Scholar, Cochrane Library, and Web of Science—up to October 2025. Two investigators independently screened eligible studies. Descriptive synthesis and meta-analysis were performed using a random-effects model. The risk of bias (RoB) was assessed with the RoB 2 tool for randomized controlled trials (RCTs) and the Joanna Briggs Institute (JBI) tool for case series. Results: The systematic review included nine studies (two RCTs and seven case series) with a total of 665 patients, 361 of whom received aviptadil. Meta-analysis of the two RCTs yielded a pooled prevalence of survival of 0.71 [95% confidence interval (CI): 0.53–0.87]. The survival odds ratio (OR) comparing aviptadil to placebo was 1.01 (95% CI: 0.72–1.42, p = 0.93), indicating no significant benefit. Across the case series, 48 of 54 patients (88.9%) survived following aviptadil therapy, demonstrating consistent improvements in oxygenation and reductions in inflammatory markers. Conclusion: Aviptadil may have a physiological role in improving oxygenation and reducing inflammation in ARDS; however, current evidence does not indicate a significant survival benefit. Larger, well-designed RCTs are needed to clarify its therapeutic potential.