VIP
VIP is a 28-amino-acid human signal; aviptadil is its synthetic drug form. A large intravenous COVID-19 trial was negative, an intracavernosal aviptadil-plus-phentolamine product has a positive erectile-dysfunction trial and national authorizations, and intranasal CIRS use lacks a registered controlled trial.
Endogenous vasoactive neuropeptide
- VIP means vasoactive intestinal peptide
- Synthetic VIP is called aviptadil
- Native peptide disappears from plasma in about one minute
- Route and co-administered drugs change the evidence
How do native VIP, aviptadil, Invicorp, and pemziviptadil differ?
Native VIP is the body's 28-amino-acid peptide. Aviptadil is synthetic VIP. Invicorp combines aviptadil with the alpha-blocker phentolamine for intracavernosal injection. Pemziviptadil is a longer-acting engineered fusion and is not interchangeable with VIP.
| Object | Route or design | What its evidence can answer |
|---|---|---|
| Native VIP | Endogenous peptide; experimental infusion or local injection | Human pharmacology and very short plasma persistence |
| Aviptadil | Synthetic VIP, studied intravenously or by inhalation | Aviptadil-specific lung trials |
| Aviptadil plus phentolamine | Fixed intracavernosal combination | Erectile-dysfunction efficacy and product safety |
| Pemziviptadil | Long-acting engineered VIP fusion | Its own development program only |
Each result applies to the listed route, formulation, and population.
Native VIP · one-minute disappearance
Human infusion study
Domschke et al., Gut, 1978
Four healthy volunteers received graded 30-minute VIP infusions. Plasma VIP fell with an average one-minute disappearance half-time; the highest dose increased pulse and blood-pressure amplitude and caused flushing.
- Participants / model
- Four healthy volunteers
- Treatment
- Intravenous native VIP at 0.6, 1.3, or 3.3 pmol/kg/min
- Follow-up
- 30-minute infusions
- Study design
- Graded human pharmacology study
The very small study does not define other routes or longer formulations.
Read the original sourceVIP plus phentolamine · placebo-controlled response
Randomized placebo-controlled combination trial
Dinsmore et al., BJU International, 1999
In 171 men, 25 micrograms aviptadil plus 1 mg phentolamine produced a response in 75% versus 12% with placebo; the 2 mg phentolamine combination produced 66% versus 18%. Flushing accompanied 40% of 1,711 injections, with one priapism episode.
- Participants / model
- Men with predominantly nonpsychogenic erectile dysfunction
- Treatment
- Intracavernosal aviptadil 25 micrograms plus phentolamine 1 or 2 mg versus placebo
- Follow-up
- Up to 12 injections over 6 months after dose assessment
- Study design
- Multicenter double-blind placebo-controlled combination study
Because both active ingredients were given together, the study does not isolate aviptadil's contribution.
Read the original sourceRoute-specific clinical programs
Trial registrations
ClinicalTrials.gov.
ClinicalTrials.gov includes aviptadil studies for intravenous and inhaled lung use and native VIP infusion research. The cited registry records include no controlled intranasal VIP study for chronic inflammatory response syndrome or mold-related illness.
This ClinicalTrials.gov result does not establish universal absence across every national registry.
Read the original sourceWhat did the largest controlled aviptadil lung trial find?
TESICO found no significant clinical benefit from three daily 12-hour intravenous aviptadil infusions in adults hospitalized with COVID-19 hypoxemic respiratory failure. The day-90 ordinal outcome odds ratio was 1.11, 95% CI 0.80 to 1.55, P = 0.54.
The modified intention-to-treat analysis included 461 people; 94% were in intensive care and 40% were invasively ventilated. By day 90, 86 of 231 aviptadil recipients and 83 of 230 placebo recipients had died, hazard ratio 1.04, 95% CI 0.77 to 1.41.
The data monitoring board stopped the aviptadil comparison for futility before its planned sample size.
TESICO · large independent null trial
Randomized placebo-controlled trial
Brown et al., Lancet Respiratory Medicine, 2023
In the 461-person modified intention-to-treat comparison, intravenous aviptadil did not improve the day-90 ordinal outcome, OR 1.11 (95% CI 0.80 to 1.55; P = 0.54). Day-90 mortality was 86 of 231 versus 83 of 230, HR 1.04 (0.77 to 1.41). The arm stopped for futility.
- Day-5 serious safety composite: 63% versus 56%, OR 1.40 (0.94 to 2.08)
- 94% were in intensive care at baseline
- Participants / model
- Hospitalized adults with COVID-19 acute hypoxemic respiratory failure
- Treatment
- Intravenous aviptadil as a 12-hour infusion on three days versus saline placebo
- Follow-up
- Primary outcome at day 90; mortality followed to day 180
- Study design
- Multicenter randomized masked placebo-controlled trial
- Funding
- U.S. National Institutes of Health
The study was stopped before the planned sample size, but its estimate excludes the large benefit it was powered to detect.
Read the original sourceWhy does an earlier COVID-19 paper sound more favorable?
A 196-person sponsor-run trial missed its primary endpoint for being alive and free of respiratory failure at day 60, odds ratio 1.6, 95% CI 0.86 to 3.11. A secondary survival analysis was positive, odds ratio 2.0, 95% CI 1.1 to 3.9, but the later, larger independent TESICO trial did not confirm benefit.
The prespecified primary endpoint failed. A positive secondary endpoint did not outweigh the later 461-person modified intention-to-treat analysis.
Earlier COVID RCT · primary endpoint missed
Randomized placebo-controlled trial
Youssef et al., Critical Care Medicine, 2022
Among 196 participants, the primary alive-and-free-of-respiratory-failure endpoint did not differ significantly, OR 1.6 (95% CI 0.86 to 3.11). A secondary survival analysis favored aviptadil, OR 2.0 (1.1 to 3.9).
- Participants / model
- Adults with critical COVID-19 respiratory failure at 10 U.S. hospitals
- Treatment
- Three days of intravenous aviptadil versus placebo
- Follow-up
- 60 days
- Study design
- Multicenter randomized 2:1 placebo-controlled trial
The positive survival finding was secondary, and the later independent TESICO trial did not confirm clinical benefit.
Read the original sourceTESICO · large independent null trial
Randomized placebo-controlled trial
Brown et al., Lancet Respiratory Medicine, 2023
In the 461-person modified intention-to-treat comparison, intravenous aviptadil did not improve the day-90 ordinal outcome, OR 1.11 (95% CI 0.80 to 1.55; P = 0.54). Day-90 mortality was 86 of 231 versus 83 of 230, HR 1.04 (0.77 to 1.41). The arm stopped for futility.
- Day-5 serious safety composite: 63% versus 56%, OR 1.40 (0.94 to 2.08)
- 94% were in intensive care at baseline
- Participants / model
- Hospitalized adults with COVID-19 acute hypoxemic respiratory failure
- Treatment
- Intravenous aviptadil as a 12-hour infusion on three days versus saline placebo
- Follow-up
- Primary outcome at day 90; mortality followed to day 180
- Study design
- Multicenter randomized masked placebo-controlled trial
- Funding
- U.S. National Institutes of Health
The study was stopped before the planned sample size, but its estimate excludes the large benefit it was powered to detect.
Read the original sourceWhat exactly worked for erectile dysfunction?
The positive result belongs to intracavernosal aviptadil plus phentolamine, not VIP alone. In the placebo-controlled phase, 75% responded to 25 micrograms aviptadil plus 1 mg phentolamine versus 12% with placebo; the 2 mg phentolamine combination produced 66% versus 18%.
The study treated 171 men for up to 12 injections over six months. Median erection duration was 56 minutes. Transient facial flushing occurred with 40% of 1,711 injections, one priapism episode occurred, and seven men withdrew for adverse events.
VIP plus phentolamine · placebo-controlled response
Randomized placebo-controlled combination trial
Dinsmore et al., BJU International, 1999
In 171 men, 25 micrograms aviptadil plus 1 mg phentolamine produced a response in 75% versus 12% with placebo; the 2 mg phentolamine combination produced 66% versus 18%. Flushing accompanied 40% of 1,711 injections, with one priapism episode.
- Participants / model
- Men with predominantly nonpsychogenic erectile dysfunction
- Treatment
- Intracavernosal aviptadil 25 micrograms plus phentolamine 1 or 2 mg versus placebo
- Follow-up
- Up to 12 injections over 6 months after dose assessment
- Study design
- Multicenter double-blind placebo-controlled combination study
Because both active ingredients were given together, the study does not isolate aviptadil's contribution.
Read the original sourceInvicorp · national combination assessment
National health-technology assessment
All Wales Therapeutics and Toxicology Centre
The assessment concerns the fixed intracavernosal aviptadil 25 microgram plus phentolamine 2 mg product for erectile dysfunction in adult men when other medical treatment is unsuitable or ineffective.
- Participants / model
- Adult men with erectile dysfunction
- Treatment
- Intracavernosal Invicorp combination
- Follow-up
- National product assessment
- Study design
- Health-technology and authorization-context document
This product decision does not apply to aviptadil alone or another route.
Read the original sourceCan the combination result be credited to VIP by itself?
In a 24-man placebo-controlled dose study, VIP alone increased penile length and diameter, but no participant achieved rigidity adequate for intercourse. The combination result therefore cannot be credited to VIP alone.
Phentolamine is an active vasodilating alpha-blocker. The combination trial cannot isolate how much of the response came from aviptadil.
VIP alone · inadequate rigidity
Randomized placebo-controlled dose study
Roy, Petrone, and Said, Journal of Urology, 1990
In 24 men, VIP alone produced dose-related changes in penile length and diameter, but no participant achieved rigidity adequate for intercourse.
- Participants / model
- Men with diabetic, neurogenic, or psychogenic erectile dysfunction
- Treatment
- Intracavernosal native VIP 200 or 400 pmol versus placebo
- Follow-up
- Three weekly visits
- Study design
- Double-blind randomized placebo-controlled study
Physiologic change did not translate into adequate rigidity.
Read the original sourceVIP plus phentolamine · placebo-controlled response
Randomized placebo-controlled combination trial
Dinsmore et al., BJU International, 1999
In 171 men, 25 micrograms aviptadil plus 1 mg phentolamine produced a response in 75% versus 12% with placebo; the 2 mg phentolamine combination produced 66% versus 18%. Flushing accompanied 40% of 1,711 injections, with one priapism episode.
- Participants / model
- Men with predominantly nonpsychogenic erectile dysfunction
- Treatment
- Intracavernosal aviptadil 25 micrograms plus phentolamine 1 or 2 mg versus placebo
- Follow-up
- Up to 12 injections over 6 months after dose assessment
- Study design
- Multicenter double-blind placebo-controlled combination study
Because both active ingredients were given together, the study does not isolate aviptadil's contribution.
Read the original sourceHas intranasal VIP been tested in a controlled CIRS trial?
The cited ClinicalTrials.gov records contain no registered controlled intranasal VIP trial for chronic inflammatory response syndrome or mold-related illness. The commonly cited clinical report followed 20 treated patients without randomization or a placebo group.
That report described before-and-after immune markers and symptom improvement with 50 micrograms four times daily. Its open-label design, small sample, protocol-author involvement, and publication outside the indexed clinical literature prevent a causal efficacy conclusion.
CIRS report · uncontrolled 20-person series
Uncontrolled clinical report
Shoemaker and House, Health, 2013
The report describes before-and-after symptoms and immune markers in 20 patients given intranasal VIP, without randomization or a placebo group.
- Participants / model
- Twenty patients labeled with chronic inflammatory response syndrome
- Treatment
- Intranasal VIP 50 micrograms four times daily
- Follow-up
- Open treatment follow-up
- Study design
- Uncontrolled open-label report
Small, unblinded, uncontrolled, and published outside the indexed mainstream clinical literature; it cannot establish efficacy.
Read the original sourceRoute-specific clinical programs
Trial registrations
ClinicalTrials.gov.
ClinicalTrials.gov includes aviptadil studies for intravenous and inhaled lung use and native VIP infusion research. The cited registry records include no controlled intranasal VIP study for chronic inflammatory response syndrome or mold-related illness.
This ClinicalTrials.gov result does not establish universal absence across every national registry.
Read the original sourceWhat does the human pharmacokinetic study show?
In four healthy volunteers receiving intravenous native VIP, plasma concentrations fell with an average disappearance half-time of about one minute after infusion stopped.
At the highest infusion dose, pulse and blood-pressure amplitude increased and flushing occurred. The tiny study explains why successful delivery cannot be assumed across intravenous, inhaled, intranasal, and intracavernosal routes.
Native VIP · one-minute disappearance
Human infusion study
Domschke et al., Gut, 1978
Four healthy volunteers received graded 30-minute VIP infusions. Plasma VIP fell with an average one-minute disappearance half-time; the highest dose increased pulse and blood-pressure amplitude and caused flushing.
- Participants / model
- Four healthy volunteers
- Treatment
- Intravenous native VIP at 0.6, 1.3, or 3.3 pmol/kg/min
- Follow-up
- 30-minute infusions
- Study design
- Graded human pharmacology study
The very small study does not define other routes or longer formulations.
Read the original sourceWhich harms are visible in the human evidence?
VIP-related vasodilation can produce flushing and circulatory effects, while product-specific risks depend on route and co-drugs. TESICO's day-5 composite of death, serious events, organ failure, serious infection, or grade 3 to 4 events occurred in 63% with aviptadil and 56% with placebo, odds ratio 1.40, 95% CI 0.94 to 2.08.
- Native intravenous VIP caused flushing and pulse and blood-pressure changes at the highest dose in a four-person study.
- The erectile-dysfunction combination commonly caused facial flushing and produced one priapism episode across 1,711 injections.
- The lung and erectile products used medical monitoring and route-specific administration; neither supplies safety instructions for an intranasal research product.
TESICO · large independent null trial
Randomized placebo-controlled trial
Brown et al., Lancet Respiratory Medicine, 2023
In the 461-person modified intention-to-treat comparison, intravenous aviptadil did not improve the day-90 ordinal outcome, OR 1.11 (95% CI 0.80 to 1.55; P = 0.54). Day-90 mortality was 86 of 231 versus 83 of 230, HR 1.04 (0.77 to 1.41). The arm stopped for futility.
- Day-5 serious safety composite: 63% versus 56%, OR 1.40 (0.94 to 2.08)
- 94% were in intensive care at baseline
- Participants / model
- Hospitalized adults with COVID-19 acute hypoxemic respiratory failure
- Treatment
- Intravenous aviptadil as a 12-hour infusion on three days versus saline placebo
- Follow-up
- Primary outcome at day 90; mortality followed to day 180
- Study design
- Multicenter randomized masked placebo-controlled trial
- Funding
- U.S. National Institutes of Health
The study was stopped before the planned sample size, but its estimate excludes the large benefit it was powered to detect.
Read the original sourceNative VIP · one-minute disappearance
Human infusion study
Domschke et al., Gut, 1978
Four healthy volunteers received graded 30-minute VIP infusions. Plasma VIP fell with an average one-minute disappearance half-time; the highest dose increased pulse and blood-pressure amplitude and caused flushing.
- Participants / model
- Four healthy volunteers
- Treatment
- Intravenous native VIP at 0.6, 1.3, or 3.3 pmol/kg/min
- Follow-up
- 30-minute infusions
- Study design
- Graded human pharmacology study
The very small study does not define other routes or longer formulations.
Read the original sourceVIP plus phentolamine · placebo-controlled response
Randomized placebo-controlled combination trial
Dinsmore et al., BJU International, 1999
In 171 men, 25 micrograms aviptadil plus 1 mg phentolamine produced a response in 75% versus 12% with placebo; the 2 mg phentolamine combination produced 66% versus 18%. Flushing accompanied 40% of 1,711 injections, with one priapism episode.
- Participants / model
- Men with predominantly nonpsychogenic erectile dysfunction
- Treatment
- Intracavernosal aviptadil 25 micrograms plus phentolamine 1 or 2 mg versus placebo
- Follow-up
- Up to 12 injections over 6 months after dose assessment
- Study design
- Multicenter double-blind placebo-controlled combination study
Because both active ingredients were given together, the study does not isolate aviptadil's contribution.
Read the original sourceWhat is the regulatory answer for each product?
No FDA-approved aviptadil or VIP drug appears in the cited US records. National authorization evidence exists for the aviptadil-plus-phentolamine intracavernosal combination used for erectile dysfunction; it does not authorize VIP alone, inhaled aviptadil, or an intranasal product.
The Welsh medicines assessment evaluates Invicorp as a fixed combination for erectile dysfunction after oral therapy is unsuitable or unsuccessful. A national combination authorization cannot be generalized to another route, formulation, or indication.
US approval status
US approval status
Drugs@FDA and openFDA.
No FDA-approved vasoactive intestinal peptide product appears in the cited US approval records.
National authorizations outside the United States are separate and product-specific.
Read the original sourceInvicorp · national combination assessment
National health-technology assessment
All Wales Therapeutics and Toxicology Centre
The assessment concerns the fixed intracavernosal aviptadil 25 microgram plus phentolamine 2 mg product for erectile dysfunction in adult men when other medical treatment is unsuitable or ineffective.
- Participants / model
- Adult men with erectile dysfunction
- Treatment
- Intracavernosal Invicorp combination
- Follow-up
- National product assessment
- Study design
- Health-technology and authorization-context document
This product decision does not apply to aviptadil alone or another route.
Read the original sourceStudies and sources
TESICO · large independent null trial
Randomized placebo-controlled trial
Brown et al., Lancet Respiratory Medicine, 2023
In the 461-person modified intention-to-treat comparison, intravenous aviptadil did not improve the day-90 ordinal outcome, OR 1.11 (95% CI 0.80 to 1.55; P = 0.54). Day-90 mortality was 86 of 231 versus 83 of 230, HR 1.04 (0.77 to 1.41). The arm stopped for futility.
- Day-5 serious safety composite: 63% versus 56%, OR 1.40 (0.94 to 2.08)
- 94% were in intensive care at baseline
- Participants / model
- Hospitalized adults with COVID-19 acute hypoxemic respiratory failure
- Treatment
- Intravenous aviptadil as a 12-hour infusion on three days versus saline placebo
- Follow-up
- Primary outcome at day 90; mortality followed to day 180
- Study design
- Multicenter randomized masked placebo-controlled trial
- Funding
- U.S. National Institutes of Health
The study was stopped before the planned sample size, but its estimate excludes the large benefit it was powered to detect.
Read the original sourceEarlier COVID RCT · primary endpoint missed
Randomized placebo-controlled trial
Youssef et al., Critical Care Medicine, 2022
Among 196 participants, the primary alive-and-free-of-respiratory-failure endpoint did not differ significantly, OR 1.6 (95% CI 0.86 to 3.11). A secondary survival analysis favored aviptadil, OR 2.0 (1.1 to 3.9).
- Participants / model
- Adults with critical COVID-19 respiratory failure at 10 U.S. hospitals
- Treatment
- Three days of intravenous aviptadil versus placebo
- Follow-up
- 60 days
- Study design
- Multicenter randomized 2:1 placebo-controlled trial
The positive survival finding was secondary, and the later independent TESICO trial did not confirm clinical benefit.
Read the original sourceVIP plus phentolamine · placebo-controlled response
Randomized placebo-controlled combination trial
Dinsmore et al., BJU International, 1999
In 171 men, 25 micrograms aviptadil plus 1 mg phentolamine produced a response in 75% versus 12% with placebo; the 2 mg phentolamine combination produced 66% versus 18%. Flushing accompanied 40% of 1,711 injections, with one priapism episode.
- Participants / model
- Men with predominantly nonpsychogenic erectile dysfunction
- Treatment
- Intracavernosal aviptadil 25 micrograms plus phentolamine 1 or 2 mg versus placebo
- Follow-up
- Up to 12 injections over 6 months after dose assessment
- Study design
- Multicenter double-blind placebo-controlled combination study
Because both active ingredients were given together, the study does not isolate aviptadil's contribution.
Read the original sourceVIP alone · inadequate rigidity
Randomized placebo-controlled dose study
Roy, Petrone, and Said, Journal of Urology, 1990
In 24 men, VIP alone produced dose-related changes in penile length and diameter, but no participant achieved rigidity adequate for intercourse.
- Participants / model
- Men with diabetic, neurogenic, or psychogenic erectile dysfunction
- Treatment
- Intracavernosal native VIP 200 or 400 pmol versus placebo
- Follow-up
- Three weekly visits
- Study design
- Double-blind randomized placebo-controlled study
Physiologic change did not translate into adequate rigidity.
Read the original sourceNative VIP · one-minute disappearance
Human infusion study
Domschke et al., Gut, 1978
Four healthy volunteers received graded 30-minute VIP infusions. Plasma VIP fell with an average one-minute disappearance half-time; the highest dose increased pulse and blood-pressure amplitude and caused flushing.
- Participants / model
- Four healthy volunteers
- Treatment
- Intravenous native VIP at 0.6, 1.3, or 3.3 pmol/kg/min
- Follow-up
- 30-minute infusions
- Study design
- Graded human pharmacology study
The very small study does not define other routes or longer formulations.
Read the original sourceCIRS report · uncontrolled 20-person series
Uncontrolled clinical report
Shoemaker and House, Health, 2013
The report describes before-and-after symptoms and immune markers in 20 patients given intranasal VIP, without randomization or a placebo group.
- Participants / model
- Twenty patients labeled with chronic inflammatory response syndrome
- Treatment
- Intranasal VIP 50 micrograms four times daily
- Follow-up
- Open treatment follow-up
- Study design
- Uncontrolled open-label report
Small, unblinded, uncontrolled, and published outside the indexed mainstream clinical literature; it cannot establish efficacy.
Read the original sourceRoute-specific clinical programs
Trial registrations
ClinicalTrials.gov.
ClinicalTrials.gov includes aviptadil studies for intravenous and inhaled lung use and native VIP infusion research. The cited registry records include no controlled intranasal VIP study for chronic inflammatory response syndrome or mold-related illness.
This ClinicalTrials.gov result does not establish universal absence across every national registry.
Read the original sourceInvicorp · national combination assessment
National health-technology assessment
All Wales Therapeutics and Toxicology Centre
The assessment concerns the fixed intracavernosal aviptadil 25 microgram plus phentolamine 2 mg product for erectile dysfunction in adult men when other medical treatment is unsuitable or ineffective.
- Participants / model
- Adult men with erectile dysfunction
- Treatment
- Intracavernosal Invicorp combination
- Follow-up
- National product assessment
- Study design
- Health-technology and authorization-context document
This product decision does not apply to aviptadil alone or another route.
Read the original sourceUS approval status
US approval status
Drugs@FDA and openFDA.
No FDA-approved vasoactive intestinal peptide product appears in the cited US approval records.
National authorizations outside the United States are separate and product-specific.
Read the original sourceWhy is VIP in D tier?
The existing D tier reflects conflicting, route-specific human evidence. The strongest lung trial was stopped for futility, the erectile-dysfunction result belongs to a two-drug intracavernosal product, and community intranasal use remains uncontrolled.