{"id":"vip","name":"VIP (vasoactive intestinal peptide)","aliases":["aviptadil","vasoactive intestinal peptide","Zyesami","RLF-100","Invicorp (with phentolamine)"],"url":"https://lyoresearch.com/compounds/vip","class":{"id":"immune-peptides","name":"Immune, antimicrobial and repair-signal peptides","url":"https://lyoresearch.com/classes/immune-peptides"},"summary":"Vasoactive intestinal peptide is a natural hormone that relaxes smooth muscle and blood vessels and dampens inflammation, made throughout the gut, lungs and nervous system. As the drug aviptadil it is licensed in the UK and some other countries — combined with phentolamine as an injection into the penis — for erectile dysfunction. Its pandemic moment came as an intravenous treatment for COVID-19 respiratory failure: the NIH-run TESICO trial of 461 patients was stopped for futility, with no improvement in outcomes or survival. The nasal-spray use promoted for 'chronic inflammatory response syndrome' from mould exposure has never been tested in a controlled trial.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"TESICO RCT (n=461) + earlier sponsor RCT; small trials in ED and pulmonary hypertension","regulatory_status":"Licensed narrowly (ED, some countries); other uses unapproved","molecule":{"formula":"C147H237N43O43S","molecular_weight":"3326.8","cas":"40077-57-4","pubchem_cid":16132300,"note":null},"pharmacokinetics":{"basis":"human","route":"Intravenous infusion (healthy volunteers); intracavernosal in the licensed product","half_life":"About 1 minute (intravenous)","licensed_regimen":null,"product":null,"source":{"title":"Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects. Gut 1978;19:1049","url":"https://pubmed.ncbi.nlm.nih.gov/730072/"}},"outcomes":[{"outcome":"COVID-19 respiratory failure (intravenous)","grade":"A","grade_meaning":"established in humans","effect_size":"not measurable","adverse":false,"human_studies":"1 large RCT (n=461) — stopped for futility","evidence":"In the NIH-funded TESICO trial, three days of intravenous aviptadil did not improve the 90-day outcome or survival; the safety monitoring board stopped it for futility. An earlier, smaller sponsor-run trial had reported benefit in some analyses.","references":[{"citation":"Brown SM, Barkauskas CE, Grund B, et al. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.","where":"Lancet Respir Med, 2023","url":"https://pubmed.ncbi.nlm.nih.gov/37348524/"},{"citation":"Youssef JG, Lavin P, Schoenfeld DA, et al. The use of IV vasoactive intestinal peptide (aviptadil) in patients with critical COVID-19 respiratory failure: results of a 60-day randomized controlled trial.","where":"Crit Care Med, 2022","url":"https://pubmed.ncbi.nlm.nih.gov/36044317/"}],"verbatim":{"text":"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).","citation":"Brown SM, Barkauskas CE, Grund B, et al. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.","url":"https://pubmed.ncbi.nlm.nih.gov/37348524/"}},{"outcome":"Survival in COVID-19 respiratory failure","grade":"A","grade_meaning":"established in humans","effect_size":"not measurable","adverse":false,"human_studies":"TESICO","evidence":"Deaths by day 90 were 38% on aviptadil and 36% on placebo.","references":[{"citation":"Brown SM, Barkauskas CE, Grund B, et al. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.","where":"Lancet Respir Med, 2023","url":"https://pubmed.ncbi.nlm.nih.gov/37348524/"}],"verbatim":{"text":"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).","citation":"Brown SM, Barkauskas CE, Grund B, et al. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.","url":"https://pubmed.ncbi.nlm.nih.gov/37348524/"}},{"outcome":"Erectile dysfunction (intracavernosal, with phentolamine)","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"Licensing trials","evidence":"The combination injection produces erections sufficient for intercourse in a majority of men in the trials behind its UK and Danish licences; a niche option where PDE5 inhibitors fail or are unsuitable.","references":[{"citation":"Invicorp (aviptadil / phentolamine) — Summary of Product Characteristics.","where":"MHRA / emc, UK","url":"https://www.medicines.org.uk/emc/search?q=invicorp"}]},{"outcome":"Pulmonary hypertension (inhaled)","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"Small studies","evidence":"Inhaled VIP lowered pulmonary pressures acutely in small open studies; a development programme did not reach approval.","references":[{"citation":"Inhaled vasoactive intestinal peptide in pulmonary hypertension — clinical studies.","where":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=inhaled+vasoactive+intestinal+peptide+pulmonary+hypertension"}]},{"outcome":"'Mould illness' / CIRS (nasal spray)","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None controlled","evidence":"The use it is most sold for online. No randomised trial exists; the diagnosis itself is not recognised by mainstream medicine. Claims rest on a single practitioner's uncontrolled case series.","references":[{"citation":"Searches of PubMed and trial registries for intranasal VIP in chronic inflammatory response syndrome or mould illness.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=vasoactive+intestinal+peptide+nasal+chronic+inflammatory+response+syndrome"}]},{"outcome":"Adverse effects","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":true,"human_studies":"TESICO + licensing data","evidence":"Flushing, low blood pressure, diarrhoea and fast heart rate with systemic doses; in TESICO the composite safety outcome was numerically worse on aviptadil without reaching significance. Intracavernosal use: pain and prolonged erection.","references":[{"citation":"Brown SM, Barkauskas CE, Grund B, et al. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.","where":"Lancet Respir Med, 2023","url":"https://pubmed.ncbi.nlm.nih.gov/37348524/"},{"citation":"Invicorp (aviptadil / phentolamine) — Summary of Product Characteristics.","where":"MHRA / emc, UK","url":"https://www.medicines.org.uk/emc/search?q=invicorp"}]}],"regions":[{"region":"European Union","status":"Authorised in some member states (ED, with phentolamine)","note":"Invicorp is licensed nationally in Denmark and others for erectile dysfunction; no authorisation for any other use."},{"region":"United States","status":"Not approved","note":"Emergency authorisation for COVID-19 was sought and not granted; no approved aviptadil product."},{"region":"United Kingdom","status":"Licensed, prescription-only (Invicorp, ED)","note":"Licensed for erectile dysfunction as an intracavernosal injection with phentolamine. Nasal VIP is unlicensed."},{"region":"Australia","status":"Not registered","note":"Not on the ARTG."},{"region":"Canada","status":"Not authorised","note":"No Health Canada authorisation."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not on the Prohibited List."}],"faq":[{"q":"Did VIP work for COVID-19?","a":"No. The NIH-funded TESICO trial of 461 patients with respiratory failure was stopped for futility: no improvement in recovery and no survival benefit. A smaller sponsor trial had suggested otherwise."},{"q":"Does nasal VIP treat mould illness or CIRS?","a":"There is no controlled trial, and the diagnosis is not recognised by mainstream medicine. The claims come from one practitioner's uncontrolled patient series."},{"q":"Is VIP approved anywhere?","a":"Yes, narrowly: as an injection into the penis, combined with phentolamine, for erectile dysfunction in the UK, Denmark and a few other countries. Not in the US, and not for any inhaled or nasal use."}],"references":[{"cite":"Brown SM, Barkauskas CE, Grund B, et al. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.","where":"Lancet Respir Med, 2023","url":"https://pubmed.ncbi.nlm.nih.gov/37348524/","note":"461 patients; stopped for futility."},{"cite":"Youssef JG, Lavin P, Schoenfeld DA, et al. The use of IV vasoactive intestinal peptide (aviptadil) in patients with critical COVID-19 respiratory failure: results of a 60-day randomized controlled trial.","where":"Crit Care Med, 2022","url":"https://pubmed.ncbi.nlm.nih.gov/36044317/","note":"Sponsor-run; the earlier, smaller trial."},{"cite":"Invicorp (aviptadil / phentolamine) — Summary of Product Characteristics.","where":"MHRA / emc, UK","url":"https://www.medicines.org.uk/emc/search?q=invicorp","note":"Licensed use in erectile dysfunction."},{"cite":"Inhaled vasoactive intestinal peptide in pulmonary hypertension — clinical studies.","where":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=inhaled+vasoactive+intestinal+peptide+pulmonary+hypertension","note":"Small studies; no approval."},{"cite":"Searches of PubMed and trial registries for intranasal VIP in chronic inflammatory response syndrome or mould illness.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=vasoactive+intestinal+peptide+nasal+chronic+inflammatory+response+syndrome","note":"No controlled trial identified."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. COVID rows carry a high-certainty null (A, effect none); ED graded B on licensing data; CIRS use D."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}