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Aviptadil: quick citable summary
Aviptadil is listed by PeptaHub as a immune peptide with a prescription legal-status classification. The page summarizes mechanism, research context, common routes, safety notes, and references for writers and AI answer engines.
PeptaHub. “Aviptadil: Mechanism, Research Context, Safety.” peptahub.com, 2026. https://peptahub.com/peptides/aviptadil. Licensed CC BY 4.0.
License: Creative Commons Attribution 4.0 International. Link back to https://peptahub.com/peptides/aviptadil.
What is Aviptadil?
Aviptadil (RLF-100) is a synthetic form of vasoactive intestinal peptide studied for ARDS and COVID-19 respiratory failure. It holds FDA Fast Track designation, but both randomised placebo-controlled COVID-19 trials missed their primary endpoints and the larger was stopped for futility.
Overview
Aviptadil (RLF-100) is a synthetic form of human vasoactive intestinal peptide (VIP), a 28-amino acid neuropeptide naturally produced throughout the lungs, gut, and nervous system. It has been studied extensively for acute respiratory distress syndrome (ARDS), COVID-19-related respiratory failure, and pulmonary arterial hypertension. It received FDA Fast Track designation for COVID-19 ARDS treatment and has been evaluated in Phase 2 and 3 clinical trials.
Mechanism of action
VIP/Aviptadil exerts pleiotropic effects in pulmonary tissue via VPAC1 and VPAC2 receptor activation, which are highly expressed on alveolar type II cells, pulmonary endothelium, and immune cells. Mechanistically, it upregulates surfactant protein synthesis (preventing alveolar collapse), inhibits pro-inflammatory cytokine production (IL-6, IL-1β, TNF-α), suppresses NLRP3 inflammasome activation, reduces macrophage-driven cytokine storm, and has been shown in preclinical studies to block SARS-CoV-2 replication in alveolar cells. It also promotes bronchodilation and vasodilation via cAMP-dependent signaling, reducing pulmonary vascular resistance. Inhalation and IV routes deliver active peptide directly to lung tissue.
Reported study ranges
| Purpose | Route | Reported range | Frequency | Notes |
|---|---|---|---|---|
| COVID-19 ARDS / acute respiratory failure (investigational IV protocol) | intravenous | 166–498 ng/kg/hr | continuous infusion over 3 days (escalating) | Day 1: 0.166 mcg/kg/hr; Day 2: 0.332 mcg/kg/hr; Day 3: 0.498 mcg/kg/hr. Administered under clinical supervision. Investigational protocol only. |
| pulmonary delivery (investigational inhaled/nasal) | nasal | 100–300 mcg | twice daily | Inhaled and intranasal delivery explored as outpatient alternatives to IV. Dose ranges vary by trial. Investigational use only. |
Reported ranges are for research context only. Consult a qualified healthcare professional before using any peptide.
Convert Aviptadil research-range units
Need to convert mg to mcg, dose volume, or U-100 syringe units? The Aviptadil dose calculator is preloaded with these ranges, or use the general dose unit converter.
Research summary
Both randomised placebo-controlled trials of aviptadil in COVID-19 respiratory failure missed their primary endpoints. In Youssef (Crit Care Med 2022), 196 patients were randomised 2:1 to IV aviptadil or placebo; the primary endpoint of being alive and free from respiratory failure at day 60 was not met (odds ratio 1.6, 95 percent CI 0.86-3.11). A secondary analysis showed roughly twice the odds of survival at day 60 (odds ratio 2.0, p=0.035) and reduced IL-6 by day 3, and the authors argued the benefit-risk balance was favourable. The larger TESICO trial (Lancet Respir Med 2023) randomised 461 patients and was stopped for futility on the recommendation of its data and safety monitoring board: the odds ratio on the primary day-90 ordinal outcome was 1.11 (95 percent CI 0.80-1.55, p=0.54), and 90-day mortality was 38 percent with aviptadil versus 36 percent with placebo. Outside COVID-19, a small inhalation study in pulmonary hypertension reported haemodynamic improvement (Leuchte, Eur Respir J 2008). Aviptadil has not received FDA or EMA approval for respiratory indications.[1][2][3][4][5]
Evidence grading
Each claimed benefit is graded by the strength of available evidence. Grades reflect study quality, not effect size.
Strong = multiple RCTs · Moderate = limited trials or observational · Preliminary = animal or in vitro only · Insufficient = anecdotal or no published data
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with Aviptadil for synergistic effects.
Legal status
Investigational drug with FDA Fast Track designation, which speeds review and is not a finding of efficacy. Available via compassionate use and expanded access protocols in the US. Not approved for general commercial sale and not approved for any pulmonary indication in the US or EU. Verify current federal and state rules before relying on access claims.
Sourcing & access
Prescription required
Aviptadil is an FDA-approved prescription medication available through licensed healthcare providers, pharmacies, and label-appropriate access programs; compounded access depends on current FDA shortage status and compounding rules.
Frequently asked questions
Aviptadil (RLF-100) is a synthetic 28-amino acid form of human vasoactive intestinal peptide (VIP). It has been studied for acute respiratory distress syndrome, COVID-19 respiratory failure, and pulmonary arterial hypertension, and received FDA Fast Track designation.
Aviptadil activates VPAC1 and VPAC2 receptors on alveolar type II cells, pulmonary endothelium, and immune cells. It upregulates surfactant production, inhibits pro-inflammatory cytokines (IL-6, TNF-alpha), suppresses NLRP3 inflammasome activation, and promotes bronchodilation via cAMP-dependent signaling.
No. As of 2026, Aviptadil has not received FDA or EMA approval for any respiratory indication. It is available through compassionate use and investigational protocols. It holds FDA Fast Track designation, which speeds review and is not a finding of efficacy; both randomised placebo-controlled trials in COVID-19 respiratory failure missed their primary endpoints, and the larger was stopped for futility.
Side effects include hypotension during IV infusion, flushing, nausea, tachycardia, headache, diarrhea, and injection site reactions. The very short half-life of 1 to 2 minutes following IV administration necessitates continuous infusion with clinical supervision, and the hypotension seen during titration reflects VIP's potent cAMP-mediated vasodilation rather than idiosyncratic toxicity.
Research references
- The use of IV vasoactive intestinal peptide (aviptadil) in patients with critical COVID-19 respiratory failure: results of a 60-day randomized controlled trialClinicalTrials.gov
- Inhalation of vasoactive intestinal peptide in pulmonary hypertensionClinicalTrials.gov
- Aviptadil: a promising treatment option for acute respiratory distress syndromeReview
- Vasoactive intestinal peptideReview
- Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trialPubMed