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phase 3Immune & Inflammation

Aviptadil

Also known as: RLF-100, Synthetic VIP, Zyesami

Aviptadil (RLF-100) is a synthetic form of vasoactive intestinal peptide (VIP), a 28-amino acid neuropeptide with potent anti-inflammatory, vasodilatory, and cytoprotective properties in lung tissue. It gained significant attention during the COVID-19 pandemic as an investigational treatment for acute respiratory distress syndrome (ARDS), receiving FDA Fast Track designation. Aviptadil preferentially binds VPAC1 receptors highly expressed on alveolar type II (AT2) cells, which are critical for surfactant production and are the primary target of SARS-CoV-2. It is currently in late-stage clinical trials for ARDS and other pulmonary conditions.

3 cited references·6 researched benefits

Quick Answer

Aviptadil (RLF-100) is a synthetic 28-amino acid vasoactive intestinal peptide (VIP) analog investigated for ARDS and critical respiratory failure. It targets VPAC1 receptors on alveolar type II cells, suppressing cytokine storm inflammation, protecting surfactant-producing pneumocytes, and promoting vasodilation in pulmonary vasculature. Aviptadil received FDA Fast Track designation for COVID-19-related ARDS. Phase 2/3 trials showed improvement in oxygenation and survival in critically ill patients.

Key Facts

Mechanism
Aviptadil binds with high affinity to VPAC1 receptors (and to a lesser extent VPAC2) on alveolar type II epithelial cells, pulmonary vascular endothelium, and immune cells. VPAC1 activation triggers cAMP-mediated anti-inflammatory cascades: suppression of TNF-alpha, IL-6, and IL-8 production by alveolar macrophages; inhibition of NF-kB nuclear translocation; and upregulation of anti-inflammatory IL-10. In the pulmonary vasculature, cAMP elevation causes smooth muscle relaxation and vasodilation, reducing pulmonary artery pressure. Aviptadil also protects AT2 cells from apoptosis by upregulating surfactant protein expression and blocking replicative senescence. Its bronchodilatory effect results from direct relaxation of airway smooth muscle independent of beta-adrenergic receptors.
Research Status
phase 3
Half-Life
~1-2 minutes (IV)
Molecular Formula
C₁₄₇H₂₃₈N₄₄O₄₃S
Primary Use
Immune & Inflammation
Table of Contents

Benefits

  • Improvement in oxygenation — phase 2/3 data showed significant improvement in PaO2/FiO2 ratio in ARDS patients within 24-72 hoursmoderate
  • Cytokine storm suppression — potently reduces TNF-alpha, IL-6, and other pro-inflammatory mediators in alveolar macrophagesmoderate
  • Protection of alveolar type II cells — prevents surfactant-producing cell death, preserving critical lung functionpreliminary
  • Reduction in time on mechanical ventilation — treated patients in trials showed faster weaning from ventilator supportmoderate
  • Pulmonary vasodilation — reduces pulmonary artery pressure and may benefit pulmonary hypertension patientspreliminary
  • Survival benefit in critical ARDS — early trial data suggested improved 28-day and 60-day survival in critically ill patientspreliminary

Dosage Protocols

RouteDosage RangeFrequencyNotes
Intravenous infusion (ARDS/critical care)50-150 pmol/kg/hourContinuous 12-hour infusion for 3 daysAdministered as a slow IV infusion in ICU settings with continuous hemodynamic monitoring. Typical protocol involves dose escalation from 50 to 100 to 150 pmol/kg/hour over 3 sequential 12-hour periods. Blood pressure monitoring is essential; infusion rate reduced or paused if systolic BP drops below 90 mmHg.
Inhaled nebulization (investigational)100-200 mcg2-3 times dailyInhaled formulation under investigation for non-critical respiratory indications. Direct pulmonary delivery may reduce systemic hypotensive effects while maintaining local anti-inflammatory benefit. Currently in clinical trials.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Hypotension — dose-dependent blood pressure reduction due to systemic vasodilation; most significant with IV infusioncommon
  • Diarrhea — VIP stimulates intestinal secretion; loose stools reported in 15-30% of patientscommon
  • Tachycardia — reflex increase in heart rate secondary to vasodilation-induced blood pressure dropcommon
  • Flushing — facial and upper body flushing related to vasodilatory effects, typically transientcommon
  • Severe hypotension — rapid IV administration can cause clinically significant drops in blood pressure requiring vasopressor supportserious

Frequently Asked Questions

Is aviptadil the same as VIP (vasoactive intestinal peptide)?
Yes, aviptadil is the pharmaceutical-grade synthetic form of the naturally occurring 28-amino acid VIP. The amino acid sequence is identical. The name "aviptadil" is the international nonproprietary name (INN) for synthetic VIP when used as a drug product. It is manufactured under GMP conditions with pharmaceutical-grade purity and stability, whereas "VIP" used in research settings may vary in quality and formulation. Some VIP products used in integrative medicine (intranasal VIP for CIRS) use the same molecule but in different formulations.
What happened with the COVID-19 ARDS trials?
Aviptadil received FDA Fast Track designation in 2020 for COVID-19-related ARDS based on its known lung-protective mechanism. Phase 2/3 trials (including the ZYESAMI trial) showed improvements in oxygenation and trends toward survival benefit in critically ill patients. However, results were mixed — the primary endpoint in the largest trial did not achieve statistical significance in the overall population, though pre-specified subgroups showed benefit. Regulatory review has been ongoing, and the development program has pivoted to include broader ARDS indications beyond COVID.
Can aviptadil be used for conditions other than ARDS?
VIP/aviptadil has potential applications beyond ARDS. Preclinical and early clinical data support investigation in pulmonary arterial hypertension (vasodilatory and anti-remodeling effects), sarcoidosis (anti-inflammatory), chronic obstructive pulmonary disease (bronchodilation and anti-inflammation), and even erectile dysfunction (VIP is a co-transmitter in penile vasodilation, and an aviptadil/phentolamine combination was previously studied). The intranasal VIP used in CIRS/mold illness protocols uses the same molecule for inflammatory modulation.

References

  1. 1
    Inhaled aviptadil for the treatment of moderate and severe COVID-19: a phase 2/3 randomized trial(2020)PubMed ↗
  2. 2
    Aviptadil (synthetic VIP) in COVID-19 respiratory failure: clinical outcomes and mechanism(2021)PubMed ↗
  3. 3
    Vasoactive intestinal peptide and lung disease: rationale for aviptadil therapy in ARDS(2020)PubMed ↗

Latest Research

Last updated: 2026-02-19