Quick summary
Aviptadil (RLF-100) is a synthetic form of vasoactive intestinal peptide (VIP) studied for ARDS, COVID-19 respiratory failure, and pulmonary arterial hypertension. It received FDA Fast Track designation for COVID-19 ARDS and has shown improved oxygenation and survival in clinical trials.
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.
Dosing protocols
| Purpose | Route | Dosage | 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. |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
A randomized controlled trial in critically ill COVID-19 patients found Aviptadil IV significantly improved oxygenation and survival versus best available therapy at 60 days. Retrospective observational data further support reduced mortality in severe viral ARDS. Phase 2b/3 trials have been conducted for COVID-19 ARDS and non-COVID ARDS. Pre-COVID research demonstrated efficacy in pulmonary arterial hypertension and sarcoidosis-related pulmonary disease. As of 2026, Aviptadil has not received full FDA or EMA approval; it is available via compassionate use and investigational protocols.[1][2][3][4]
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. Available via compassionate use / expanded access protocols in the US. Not approved for general commercial sale. Approved as a pharmaceutical in some European jurisdictions for pulmonary applications. RLF-100 remains under regulatory review.
Sourcing & access
Prescription required
Aviptadil is an FDA-approved prescription medication available through licensed healthcare providers, telehealth platforms, and 503A/503B compounding pharmacies.
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 full FDA or EMA approval. It is available through compassionate use and investigational protocols and has FDA Fast Track designation for COVID-19 ARDS.
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