NCT07317050

Clinical Trial With Aprotinin in the Acute Respiratory Distress Syndrome Treatment

Aprotinin Treatment of Acute Respiratory Distress Syndrome: a Multicenter, Double-blind, Placebo-controlled, Phase III Trial

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 156 (estimated)
• Sponsor: Fundacion del Hospital Nacional de Paraplejicos para la Investigacion y la Integracion · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a multicentre, double-blind, placebo-controlled Phase III randomized clinical trial designed to evaluate the efficacy and safety of inhaled aprotinin in adult patients with moderate or severe acute respiratory distress syndrome (ARDS). A total of 156 critically ill patients admitted to intensive care units will be randomized to receive either inhaled aprotinin or placebo in addition to standard supportive care. The primary objective is to determine whether aprotinin improves clinical outcomes based on a composite endpoint of mortality and ventilator-free days at 28 days.

Detailed description

This study is a nation-wide, multicentre, double-blind, placebo-controlled, Phase III randomized clinical trial designed to investigate the efficacy and safety of inhaled aprotinin in adult patients diagnosed with moderate or severe acute respiratory distress syndrome (ARDS). ARDS is a heterogeneous acute inflammatory lung syndrome characterized by diffuse alveolar damage, increased vascular permeability, alveolar and interstitial edema, and severe hypoxemic respiratory failure. Despite advances in supportive care, no specific pharmacological therapy has demonstrated proven benefit. Aprotinin is a broad-spectrum serine protease inhibitor that targets the kallikrein-kinin system and attenuates systemic inflammatory responses, including reductions in pro-inflammatory cytokines and matrix metalloproteinases (MMPs). Experimental and clinical data suggest that MMP overexpression contributes to tissue damage, coagulation abnormalities, and impaired lung repair, representing a potential therapeutic target in ARDS. Inhaled aprotinin has been used clinically in patients with respiratory conditions, including COVID-19 and chronic pulmonary disease, with no reported adverse events via this route of administration. In this trial, 156 ICU patients with moderate or severe ARDS will be enrolled and randomized in a 1:1 ratio to receive either inhaled aprotinin or placebo, both administered alongside standard supportive care. The aprotinina dosing regimen will be four inhaled doses of 500 KIU every six hours (total 2,000 KIU/day), selected to achieve effective local pulmonary concentrations while minimizing systemic exposure. The primary endpoint is a composite of mortality and ventilator-free days at 28 days among survivors. Secondary outcomes include ICU and hospital mortality, duration of mechanical ventilation, and other clinically relevant respiratory and functional endpoints. Detailed study procedures, dosing, and administration are described in the study protocol. All study procedures will be conducted under a double-blind design. Patients will be prospectively followed for clinical outcomes during their ICU and hospital stay according to prespecified assessment timepoints. A Data Monitoring Committee (DMC) composed of independent clinical experts will periodically review safety and efficacy data, ensuring the protection of participants and the scientific validity of the study. The estimated study duration is four years, from September 2025 to September 2029.

Conditions

• Acute Respiratory Distress Syndrome (ARDS)

Interventions

Type	Name	Description
DRUG	Aprotinin (inhaled)	Inhaled aprotinin, diluted in 0.9% sodium chloride, is administrated via nebulization through an endotracheal or tracheostomy tube. The dose is 500 UI every 6 hours (totaling 2,000 UI/day) for six consecutive days. Each administration consists of a nebulized inhalation lasting no less than six minutes, with four inhalations delivered per day. Nebulization is performed using Aerogen® Solo vibrating mesh nebulizers to maintain a closed ventilatory circuit. The device produces aerosol particles with a median diameter of 2-10 µm; 30-50% of these aggregates reach diameters of 50-100 µm. Administration follows pharmacy blinding procedures. All patients receive standard supportive care according to local practice.
DRUG	Placebo (Sodium Chloride)	Placebo (sodium chloride) is administered by inhalation via endotracheal or tracheostomy tube using the Aerogen® Solo vibrating mesh nebulizer, four times daily for six consecutive days. It is delivered following the same dosing schedule, device specifications, and administration procedures as the active treatment. Administration follows pharmacy blinding procedures to maintain double-blind conditions. All patients receive standard supportive care according to local practice.

Timeline

• Start date: 2026-03-01
• Primary completion: 2030-03-01
• Completion: 2030-03-01
• First posted: 2026-01-05
• Last updated: 2026-01-12

Locations

1 site across 1 country: Spain