Key papers ✓ 2✗ 2~ 1? 2

• ✗ Negative human RCTLancet Respir Med · 2023

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

  Humans473 peopleRandomizedPlacebo-controlledPrimary outcome at day 90; aviptadil infused daily for 3 days

  Randomised, placebo-controlled trial (TESICO), 2 × 2 factorial for aviptadil and remdesivir

  TESICO trial in 461 ICU patients with COVID-19 respiratory failure: IV aviptadil did not improve 90-day recovery (OR 1.11, p=0.54); mortality was 38% vs 36% on placebo, and early serious adverse events were numerically more frequent (63% vs 56%, p=0.10).

  Key resultOdds ratio for better category with aviptadil vs placebo 1·11 (95% CI 0·80-1·55; p=0·54); 90-day mortality 38% vs 36% (hazard ratio 1·04, 95% CI 0·77-1·41; p=0·78)

  Study details

  Studied

  Hospitalised adults with COVID-19 acute hypoxaemic respiratory failure at 28 US sites

  Compared with

  Matched saline placebo

  Main outcome

  Six-category ordinal outcome at day 90 (home and off oxygen through death)

  Sample

  473 enrolled; 471 randomized to aviptadil or placebo (461 in modified ITT); 87 to remdesivir comparison

  Authors' conclusion

  Aviptadil did not significantly improve clinical outcomes up to day 90 compared with placebo in COVID-19 respiratory failure.

  Limitations

  Aviptadil trial stopped for futility; remdesivir comparison underpowered (87 participants).

  DOI 10.1016/S2213-2600(23)00147-9PubMed 37348524Free full text
• ✗ Negative meta-analysisIndian J Crit Care Med · 2025

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

  Humans665 people9 studies pooled

  Systematic review and meta-analysis (random-effects)

  Meta-analysis of 9 studies (2 RCTs, 7 case series; 665 ARDS patients): pooled RCT survival odds were unchanged vs placebo (OR 1.01); uncontrolled case series reported better oxygenation.

  Key resultSurvival odds ratio aviptadil vs placebo 1.01 (95% CI: 0.72-1.42, p = 0.93); 48 of 54 patients (88.9%) survived in case series

  Study details

  Studied

  Patients with acute respiratory distress syndrome treated with aviptadil

  Compared with

  Placebo (in the two RCTs)

  Main outcome

  Survival and oxygenation

  Sample

  9 studies (2 RCTs, 7 case series), 665 patients, 361 received aviptadil

  Authors' conclusion

  Aviptadil may have a physiological role in improving oxygenation and reducing inflammation in ARDS, but current evidence does not show a significant survival benefit; larger RCTs are needed.

  Limitations

  Only two RCTs; most data from case series.

  DOI 10.5005/jp-journals-10071-25084PubMed 41368449Free full text
• ~ Mixed human RCTCrit Care Med · 2022

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

  Humans196 peopleRandomizedPlacebo-controlled60 days

  Multicenter placebo-controlled randomized trial; 3 days of IV aviptadil

  Trial in 196 patients with critical COVID-19 respiratory failure: 3 days of IV aviptadil did not meet the primary endpoint (alive and free of respiratory failure at day 60), though a secondary analysis showed 2-fold higher odds of survival; no drug-related serious adverse events.

  Key resultPrimary endpoint not significant (OR, 1.6; 95% CI, 0.86-3.11); survival OR 2.0 (95% CI 1.1-3.9, p = 0.035)

  Study details

  Studied

  Patients with COVID-19 respiratory failure at ten US hospitals

  Compared with

  Placebo

  Main outcome

  Alive and free from respiratory failure at day 60

  Sample

  196 patients randomized 2:1

  Authors' conclusion

  The primary end point was not met, but the authors conclude aviptadil improves likelihood of survival from respiratory failure at day 60 and has an acceptable safety profile.

  Limitations

  Primary end point not significant; survival and subgroup results are secondary/subgroup findings.

  DOI 10.1097/CCM.0000000000005660PubMed 36044317Free full text
• ? Inconclusive human trialEur Respir J · 2008

  Inhalation of vasoactive intestinal peptide in pulmonary hypertension.

  Humans20 peopleNo control groupSingle dose

  Single-dose acute haemodynamic study during right-heart catheterisation; inhaled aviptadil 100 microg

  Single 100-microgram inhaled dose in 20 patients with pulmonary hypertension: a small, temporary pulmonary vasodilation and improved stroke volume, with no side effects; longer-term effects untested.

  Key resultSix patients had a pulmonary vascular resistance reduction of >20%

  Study details

  Studied

  Patients with pulmonary arterial hypertension (nine), PH in lung disease (eight) or chronic thromboembolic PH (three)

  Main outcome

  Haemodynamics, blood gases and safety

  Sample

  20 patients with pulmonary hypertension

  Authors' conclusion

  The pulmonary vasodilating effect was modest and short-lived without side-effects; further studies are needed, including higher doses and chronic treatment.

  Limitations

  Single dose, no control group, 20 patients.

  DOI 10.1183/09031936.00050008PubMed 18978135
• ✓ Positive human observationalJ Sex Med · 2025

  Intracavernosal injection of aviptadil and phentolamine for refractory erectile dysfunction.

  Humans308 peopleEfficacy at 3 months; mean follow-up 13.3 months

  Retrospective single-center analysis of aviptadil plus phentolamine (AvP) intracavernosal injection

  Retrospective study of men with erectile dysfunction who failed or could not tolerate alprostadil injections: aviptadil plus phentolamine injection worked in 76% of those with pain and 36% of those with treatment failure; facial flushing in 22.5%, priapism in 0.3%.

  Key result182 men (59%) found AvP effective; efficacy 76% in the pain group vs 36% in the failed-dose group (P < .0001)

  Study details

  Studied

  Men with refractory erectile dysfunction who had pain with or failed maximal-dose alprostadil injection

  Compared with

  None (comparison of pain group vs failed-dose group)

  Main outcome

  Resumption of penetrative sexual activity

  Sample

  308 men included

  Authors' conclusion

  AvP is an effective, well-accepted second-line option for men who failed most nonsurgical treatments for ED.

  Limitations

  Retrospective design, no control group and no validated instruments to assess erectile function; combination with phentolamine.

  DOI 10.1093/jsxmed/qdaf067PubMed 40192471
• ? Inconclusive human observationalIndian J Crit Care Med · 2024

  Effect of Aviptadil, a Novel Therapy, on Clinical Outcomes of Patients with Viral-related Severe ARDS: A Retrospective Observational Study.

  Humans6 people3-day infusion

  Retrospective observational study; aviptadil infusion for 3 days plus conventional treatment

  Retrospective single-center series of severe viral ARDS patients given aviptadil: oxygenation and chest X-ray scores improved over 3 days with no adverse effects noted; no control group.

  Key resultPaO2 rose from 54.32 to 68.4 (p-value < 0.004); S/F ratio from 149 to 336 (p-value < 0.003)

  Study details

  Studied

  Patients with severe viral-related ARDS in the ICU

  Compared with

  Before vs after treatment (no control group)

  Main outcome

  Oxygenation (SpO2, PaO2, S/F ratio), radiological clearance

  Sample

  6 patients with severe ARDS among 68 viral pneumonia ICU admissions

  Authors' conclusion

  Aviptadil improved clinical outcomes in severe viral ARDS without adverse effects in this small retrospective series.

  Limitations

  Only 6 patients; retrospective, no control group.

  DOI 10.5005/jp-journals-10071-24594PubMed 38510776Free full text
• ✓ Positive human RCTMed Princ Pract · 2025

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

  Humans80 peopleRandomizedPlacebo-controlledDouble-blind30 days to discharge; CT follow-up to day 28

  Multicenter randomized, double-blind, placebo-controlled trial (1:1), added to standard care

  Multicenter double-blind randomized trial of inhaled aviptadil vs placebo in 80 hospitalized COVID-19 patients: mean time to discharge 7.8 vs 10 days (p=0.049) and greater CT improvement at day 28 (p=0.028); small trial, in contrast with the negative IV trials.

  Key resultMean time to discharge 7.8 vs 10 days (p = 0.049); death rate 5.1% vs 12.2%

  Study details

  Studied

  Hospitalized adults with COVID-19 pneumonia at 9 centers

  Compared with

  Placebo

  Main outcome

  Time from hospitalization to discharge within 30 days

  Sample

  80 hospitalized adults with COVID-19

  Authors' conclusion

  The authors conclude inhaled aviptadil is well tolerated and can be a supplementary intervention to hasten respiratory recovery in COVID-19 pneumonia.

  Limitations

  Small trial with borderline p-value on the primary endpoint; mortality difference not tested in the abstract.

  DOI 10.1159/000543773PubMed 39870064Free full text

Reported side effects

• commonFacial flushing (with phentolamine injection) [ref]
• rarePriapism (with phentolamine injection) [ref]

In the largest IV trial, serious adverse events in the first 5 days were numerically but not significantly more frequent with aviptadil than placebo.

43 registered human trials (4 active)

✓ positive · ✗ negative · ~ mixed · ? inconclusive, judged on each paper's own main outcome. Grades: A strong human evidence → D little or none. Papers and verdicts are drawn from PubMed, Europe PMC and Russian journals (CyberLeninka); not medical advice.