VIP

Vasoactive intestinal Peptide as a diagnostic or prognostic biomarker in multiple sclerosis: A systematic review.

2026 · Preclinical

Inhaled Aviptadil Is a New Hope for Recovery of Lung Damage due to COVID-19.

2025 · Medical principles and practice : international journal of the Kuwait University, Health Science Centre · Human evidence

Objective We are still in search of new therapeutic options for COVID-19 to prevent new infections, enable fast recovery, and reduce the long-lasting symptoms or sequelae. This study aimed to investigate the short- and long-term effects of inhaled aviptadil on hospitalized, adult COVID-19 patients. Methods A multicenter, prospective, placebo-controlled, comparative, randomized, double-blind clinical trial was conducted. Patients were randomized 1:1 to either inhaled aviptadil or placebo, in addition to the standard care. The primary endpoint is the time from hospitalization to discharge within 30 days of treatment. The secondary endpoints are clinical and radiological score improvements. Results The study involved 80 patients enrolled from 9 clinical centers. The mean age was 55.8 ± 18.5 years, and 27 of them (33.8%) were female. The average time to discharge was 7.8 ± 4.0 days in aviptadil group and 10 ± 5.0 days in placebo (p = 0.049). Modified Borg scales were not statistically different on day 3 (p = 0.090), but significantly lower in the aviptadil group on day 7 (p = 0.033). The CT lung damage score was not different on day 1 for both groups (p = 0.962); improvement on day 28 was significantly greater in the aviptadil group (p = 0.028). The death rate was also lower in the aviptadil group (5.1%) when compared to the placebo (12.2%). There was no drop-out due to side effects. Conclusion Study shows that inhaled aviptadil is well tolerated and can be used as a supplementary intervention to fasten the recovery of respiratory manifestations in hospitalized patients for COVID-19 pneumonia. Objective We are still in search of new therapeutic options for COVID-19 to prevent new infections, enable fast recovery, and reduce the long-lasting symptoms or sequelae. This study aimed to investigate the short- and long-term effects of inhaled aviptadil on hospitalized, adult COVID-19 patients. Methods A multicenter, prospective, placebo-controlled, comparative, randomized, double-blind clinical trial was conducted. Patients were randomized 1:1 to either inhaled aviptadil or placebo, in addition to the standard care. The primary endpoint is the time from hospitalization to discharge within 30 days of treatment. The secondary endpoints are clinical and radiological score improvements. Results The study involved 80 patients enrolled from 9 clinical centers. The mean age was 55.8 ± 18.5 years, and 27 of them (33.8%) were female. The average time to discharge was 7.8 ± 4.0 days in aviptadil group and 10 ± 5.0 days in placebo (p = 0.049). Modified Borg scales were not statistically different on day 3 (p = 0.090), but significantly lower in the aviptadil group on day 7 (p = 0.033). The CT lung damage score was not different on day 1 for both groups (p = 0.962); improvement on day 28 was significantly greater in the aviptadil group (p = 0.028). The death rate was also lower in the aviptadil group (5.1%) when compared to the placebo (12.2%). There was no drop-out due to side effects. Conclusion Study shows that inhaled aviptadil is well tolerated and can be used as a supplementary intervention to fasten the recovery of respiratory manifestations in hospitalized patients for COVID-19 pneumonia.

Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.

2023 · The Lancet. Respiratory medicine · Human evidence

Background There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure. Methods TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA. Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure. Participants could be randomly assigned to both study treatments in a 2 × 2 factorial design or to just one of the agents. Participants were randomly assigned with a web-based application. For each site, randomisation was stratified by disease severity (high-flow nasal oxygen or non-invasive ventilation vs invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), and four strata were defined by remdesivir and aviptadil eligibility, as follows: (1) eligible for randomisation to aviptadil and remdesivir in the 2 × 2 factorial design; participants were equally randomly assigned (1:1:1:1) to intravenous aviptadil plus remdesivir, aviptadil plus remdesivir matched placebo, aviptadil matched placebo plus remdesvir, or aviptadil placebo plus remdesivir placebo; (2) eligible for randomisation to aviptadil only because remdesivir was started before randomisation; (3) eligible for randomisation to aviptadil only because remdesivir was contraindicated; and (4) eligible for randomisation to remdesivir only because aviptadil was contraindicated. For participants in strata 2-4, randomisation was 1:1 to the active agent or matched placebo. Aviptadil was administered as a daily 12-h infusion for 3 days, targeting 600 pmol/kg on infusion day 1, 1200 pmol/kg on day 2, and 1800 pmol/kg on day 3. Remdesivir was administered as a 200 mg loading dose, followed by 100 mg daily maintenance doses for up to a 10-day total course. For participants assigned to placebo for either agent, matched saline placebo was administered in identical volumes. For both treatment comparisons, the primary outcome, assessed at day 90, was a six-category ordinal outcome: (1) at home (defined as the type of residence before hospitalisation) and off oxygen (recovered) for at least 77 days, (2) at home and off oxygen for 49-76 days, (3) at home and off oxygen for 1-48 days, (4) not hospitalised but either on supplemental oxygen or not at home, (5) hospitalised or in hospice care, or (6) dead. Mortality up to day 90 was a key secondary outcome. The independent data and safety monitoring board recommended stopping the aviptadil trial on May 25, 2022, for futility. On June 9, 2022, the sponsor stopped the trial of remdesivir due to slow enrolment. The trial is registered with ClinicalTrials.gov, NCT04843761. Findings Between April 21, 2021, and May 24, 2022, we enrolled 473 participants in the study. For the aviptadil comparison, 471 participants were randomly assigned to aviptadil or matched placebo. The modified intention-to-treat population comprised 461 participants who received at least a partial infusion of aviptadil (231 participants) or aviptadil matched placebo (230 participants). For the remdesivir comparison, 87 participants were randomly assigned to remdesivir or matched placebo and all received some infusion of remdesivir (44 participants) or remdesivir matched placebo (43 participants). 85 participants were included in the modified intention-to-treat analyses for both agents (ie, those enrolled in the 2 x 2 factorial). For the aviptadil versus placebo comparison, the median age was 57 years (IQR 46-66), 178 (39%) of 461 participants were female, and 246 (53%) were Black, Hispanic, Asian or other (vs 215 [47%] White participants). 431 (94%) of 461 participants were in an intensive care unit at baseline, with 271 (59%) receiving high-flow nasal oxygen or non-invasive ventiliation, 185 (40%) receiving invasive mechanical ventilation, and five (1%) receiving ECMO. The odds ratio (OR) for being in a better category of the primary efficacy endpoint for aviptadil versus placebo at day 90, from a model stratified by baseline disease severity, was 1·11 (95% CI 0·80-1·55; p=0·54). Up to day 90, 86 participants in the aviptadil group and 83 in the placebo group died. The cumulative percentage who died up to day 90 was 38% in the aviptadil group and 36% in the placebo group (hazard ratio 1·04, 95% CI 0·77-1·41; p=0·78). The primary safety outcome of death, serious adverse events, organ failure, serious infection, or grade 3 or 4 adverse events up to day 5 occurred in 146 (63%) of 231 patients in the aviptadil group compared with 129 (56%) of 230 participants in the placebo group (OR 1·40, 95% CI 0·94-2·08; p=0·10). Interpretation Among patients with COVID-19-associated acute hypoxaemic respiratory failure, aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo. The smaller than planned sample size for the remdesivir trial did not permit definitive conclusions regarding safety or efficacy. Funding National Institutes of Health.

The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial.

2022 · Critical care medicine · Human evidence

Objectives Respiratory failure is a lethal complication of COVID-19 that has remained resistant to drug therapy. Vasoactive intestinal peptide (VIP) is shown in nonclinical studies to upregulate surfactant production, inhibit cytokine synthesis, prevent cytopathy, and block replication of the severe acute respiratory syndrome coronavirus 2 virus in pulmonary cells. The study aims to determine whether Aviptadil (synthetic VIP) can improve survival and recovery in patients with COVID-19 respiratory failure compared with placebo and demonstrate biological effects in such patients. Design A multicenter, placebo-controlled trial. Setting Ten U.S. hospitals: six tertiary-care hospitals and four community hospitals. Patients A total of 196 patients with COVID-19 respiratory failure. Interventions Participants were randomized 2:1 to receive 3 days of IV Aviptadil or placebo. Measurements and main results The primary end point (alive and free from respiratory failure at day 60) did not reach statistical significance (odds ratio [OR], 1.6; 95% CI, 0.86-3.11) for patients treated with Aviptadil when controlling for baseline ventilation status as prespecified in the protocol. There was, however, a statistically significant two-fold odds of improved survival (OR, 2.0; 95% CI, 1.1-3.9) at 60 days ( p = 0.035). There was significant improvement in respiratory distress ratio and reduced interleukin 6 cytokine release ( p = 0.02) by day 3.Subgroup analysis identified a statistically significant likelihood of achieving primary end point among those treated with high-flow nasal oxygen at baseline ( p = 0.039). Subjects on mechanical ventilation also experienced a 10-fold increased odds of survival with drug versus placebo ( p = 0.031). Conclusions The primary end point did not reach statistical significance, indicating that there was no difference between Aviptadil versus placebo. However, Aviptadil improves the likelihood of survival from respiratory failure at day 60 in critical COVID-19 across all sites of care. Given the absence of drug-related serious adverse events and acceptable safety profile, we believe the benefit versus risk for the use of Aviptadil is favorable for patient treatment.

Inhaled vasoactive intestinal peptide exerts immunoregulatory effects in sarcoidosis.

2010 · American journal of respiratory and critical care medicine · Preclinical

Rationale Previous studies suggest an important immunoregulatory role of vasoactive intestinal peptide (VIP) in experimental models of chronic noninfectious inflammation. Sarcoidosis is characterized by noncaseating epitheloid cell granulomas, where excessive tumor necrosis factor-alpha production by pulmonary macrophages plays a critical role in granuloma formation and disease progression, which may lead to fatal organ dysfunction. Objectives To test whether inhaled VIP has an immunoregulatory role. Sarcoid alveolitis was used as a prototype of immune-mediated chronic lung inflammation. Methods In an open clinical phase II study, we treated 20 patients with histologically proved sarcoidosis and active disease with nebulized VIP for 4 weeks. Measurements and main results VIP inhalation was safe, well-tolerated, and significantly reduced the production of tumor necrosis factor-alpha by cells isolated from bronchoalveolar lavage fluids of these patients. VIP treatment significantly increased the numbers of bronchoalveolar lavage CD4(+)CD127(-)CD25(+) T cells, which showed regulatory activities on conventional effector T cells. In vitro experiments demonstrated the capacity of VIP to convert naive CD4(+)CD25(-) T cells into CD4(+)CD25(+)FoxP3(+) regulatory T cells, suggesting the generation of peripheral regulatory T cells by VIP treatment. Conclusions This study is the first to show the immunoregulatory effect of VIP in humans, and supports the notion of inhaled VIP as an attractive future therapy to dampen exaggerated immune responses in lung disorders. Thus, the inhalation of neuropeptides may be developed into a new therapeutic principle for chronic inflammatory lung disorders in humans.