What is VIP (vasoactive intestinal peptide)? Aviptadil, COVID trials and the evidence

Vasoactive intestinal peptide (VIP) is a 28-amino-acid signalling peptide your body makes, and aviptadil is its synthetic form. It has been tested in people for lung disease, most prominently COVID-19 respiratory failure, where the largest US trial found no benefit over placebo. Its developer reports that FDA declined an emergency use authorization in 2021, and we found no FDA-approved aviptadil product. The one approved use we could source is outside the US, in a combination product for erectile dysfunction. Claims that VIP treats mold-related illness rest on small open-label studies.

What VIP is and how it works

VIP is a 28-amino-acid neuropeptide and neurotransmitter found widely in the central and peripheral nervous system. It is also released by immune cells, and cells of the immune system carry receptors for it. Its effects include acting as a vasodilator, an immune regulator and a secretagogue, meaning something that prompts secretion (Delgado and Ganea, Amino Acids, 2013). In the lungs, reviews describe bronchodilating and vasodilating effects and anti-inflammatory, immunomodulatory actions, which is why lung disease became the main target (Mathioudakis et al., Hippokratia, 2013).

Aviptadil is the drug name for synthetic VIP (Youssef et al., Critical Care Medicine, 2022). So a vial labelled "VIP" and a trial drug called aviptadil are meant to be the same peptide. The trial results describe pharmaceutical preparations; they can't tell you what is in a research vial, which is what a lab report is for.

The physiology also has a downside worth knowing. A rare tumor that secretes VIP, called a VIPoma, produces refractory watery diarrhea, low potassium and metabolic acidosis (Una Cidon, World Journal of Gastrointestinal Oncology, 2022). That is a tumor syndrome, not a report from anyone using a vial, but it shows VIP is a potent signal, not a gentle supplement.

What people use it for

What the research actually shows

COVID-19 respiratory failure

This is the trial history that matters most. A phase 2/3 study in 10 US hospitals randomized 196 patients with critical COVID-19 respiratory failure, two to one, to a short course of intravenous aviptadil or placebo. The primary endpoint, being alive and free of respiratory failure at day 60, did not reach statistical significance (odds ratio 1.6, 95% CI 0.86 to 3.11). The authors highlighted a significant survival difference at 60 days (odds ratio 2.0), a secondary result, and concluded the primary endpoint showed no difference (Youssef et al., 2022).

The confirmation trial, TESICO, was NIH-funded and ran at 28 US sites and enrolled 473 patients, with 461 in the aviptadil analysis. It found no meaningful difference from placebo on the day-90 ordinal outcome (odds ratio 1.11, 95% CI 0.80 to 1.55), and deaths up to day 90 were 38% with aviptadil versus 36% with placebo. The independent safety board recommended stopping the aviptadil trial on May 25, 2022 for futility (Brown et al., 2023). An accompanying commentary was titled "A negative trial for vasoactive intestinal peptide in COVID-19-associated acute hypoxaemic respiratory failure" (Lee and Slutsky, Lancet Respiratory Medicine, 2023). A 2025 systematic review pooled the two randomized trials and found no significant survival benefit (odds ratio 1.01, 95% CI 0.72 to 1.42) (Udupa et al., Indian Journal of Critical Care Medicine, 2025).

A smaller, separate randomized trial of inhaled aviptadil in 80 hospitalized COVID-19 patients reported a shorter time to discharge (7.8 versus 10 days, P = 0.049) (Esendagli et al., Medical Principles and Practice, 2025). It is a single small study, and a published letter has raised methodological questions about it, so it does not overturn TESICO.

FDA's actions on aviptadil

We could not find an FDA document about aviptadil itself, so this account comes from the developer's own annual reports filed with the SEC and should be read as the company's description. NRx Pharmaceuticals, which developed the intravenous product under the name Zyesami, applied for an emergency use authorization on May 31, 2021. It reported that in November 2021 FDA said it was unable to issue the authorization at that time because of insufficient data on the known and potential benefits and risks in critical COVID-19 with respiratory failure (NRx 10-K for 2021, filed March 31, 2022). It filed a narrower request in February 2022. A year later the company reported that it had suspended its efforts to develop aviptadil for all indications in 2022 and transferred its aviptadil assets to Relief Therapeutics in December 2022 (NRx 10-K for 2022, filed March 31, 2023). We found no aviptadil or VIP entry in DailyMed as an approved drug (the only VIP-titled record was a 2017 powder listing with no label text), and openFDA's Drugs@FDA search found no match for aviptadil. FDA's page on bulk substances that may present significant safety risks (content current as of April 22, 2026) does not list VIP or aviptadil (FDA, 2026).

Erectile dysfunction: the approved use outside the US

The one approval we could source is a combination of aviptadil and phentolamine injected into the penis. A 2019 systematic review of injectable erectile dysfunction treatments notes that approval of such agents is mainly limited to alprostadil, with "the recent addition of aviptadil/phentolamine combination therapy in a select few geographical regions" (Duncan et al., 2019). A 2025 retrospective analysis of 308 men who had failed or could not tolerate alprostadil injections found the aviptadil-phentolamine product (Invicorp) effective in 59%, with facial flushing the most common adverse event (22.5%) and one case of ischemic priapism (0.3%). The authors noted the retrospective design and lack of validated instruments (Al-Mitwalli et al., 2025). This is a specific pharmaceutical combination, not evidence for VIP on its own.

Lung conditions beyond COVID-19

Older human studies were small and short. In 20 patients with chronic pulmonary hypertension, a single inhaled dose of aviptadil produced a small, temporary pulmonary vasodilation with no side effects reported, and the authors called the effect modest and short-lived (Leuchte et al., 2008). In an open-label phase 2 study of 20 people with active sarcoidosis, a short course of inhaled VIP was well tolerated and reduced inflammatory signaling in lung fluid cells (Prasse et al., 2010). Those are open-label studies with laboratory endpoints, not trials showing patients felt or did better. A 2013 review lists asthma, COPD, cystic fibrosis, pulmonary hypertension and sarcoidosis as areas of research interest and describes the clinical trials as limited (Mathioudakis et al., 2013).

Mold-related illness (CIRS)

The most common reason people go looking for VIP outside a hospital is CIRS, a diagnosis defined as immune dysregulation after exposure to water-damaged buildings. A 2024 literature review of CIRS treatments describes VIP as one step of a multi-part protocol and describes it as obtainable only through compounding pharmacies and not covered by insurance. Its evidence table lists the VIP studies as open-label trials and case series of about 20 and 35 patients, graded Level IV in the review's own scheme (reviews and single cases rank lower still), and it notes light-headedness as a side effect (Dooley et al., 2024). We found no placebo-controlled randomized trial of VIP for CIRS in our Europe PMC searches. Read the claim as unproven, not disproven.

Side effects and risks

• In the COVID-19 trials. The primary safety outcome in TESICO (death, serious adverse events, organ failure, serious infection or severe adverse events up to day 5) occurred in 63% of the aviptadil group and 56% of the placebo group, a difference that did not reach statistical significance (odds ratio 1.40, 95% CI 0.94 to 2.08) (Brown et al., 2023). The earlier phase 2/3 trial reported no drug-related serious adverse events (Youssef et al., 2022). These were critically ill patients.
• Injection and inhaled studies. Flushing and, rarely, priapism were reported with the erectile dysfunction combination (Al-Mitwalli et al., 2025). The inhaled studies above reported no side effects in their small samples (Leuchte et al., 2008).
• Unknowns. We found no long-term safety data and no safety data in healthy people using unregulated vials.
• Regulatory status. We found no FDA-approved aviptadil product, and FDA declined an emergency authorization for the COVID-19 indication in 2021, per the developer's own filing.

What the lab tests show

As of September 29, 2026, VendorVerify's database has one VIP vial, from August 2026: 99.61% pure and about 4% under its labelled amount. One vial tells you nothing about how vendors behave, so we draw no conclusions from it. If you have had a VIP vial tested, submitting the report is the fastest way to fill this gap.

Because we don't have enough lab data on this compound to rank vendors for it, here are the highest-ranked vendors across all compounds right now. A vendor's overall record is a signal, not a guarantee for a compound they have never had tested.

Buying smarter

With almost no compound-specific data, lean on the general checks. Look at each vendor's full record and the VIP results page, and check how many reports sit behind any score. Treat a vendor-posted COA as a starting point (how to read a peptide COA, fake peptide COAs). A 28-amino-acid peptide with a single result in our data is a good candidate for paying for identity, purity and quantity testing on your own vial: how to get a peptide tested walks through it, and endotoxin in research peptides covers when to add that test. If a report comes back with a fail, stop using that batch, tell anyone who bought from the same run, bring the report to the vendor, and submit it to VendorVerify.

Readers looking at anti-inflammatory peptides often also read about KPV, ARA-290 and LL-37. The peptide hub lists every compound we track.

Database figures are from VendorVerify as of September 29, 2026. This isn't medical advice; VIP has no FDA approval we could find, and its largest COVID-19 trial was negative.