Clinical Trial With Aprotinin in the Acute Respiratory Distress Syndrome Treatment

NCT07317050 | Not Yet Recruiting Phase 3

• 2 other identifiers: ICI24/000112025-520826-39-00
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Respiratory Distress Syndrome (ARDS)

Keywords

Acute Respiratory Distress Syndrome (ARDS); Inhaled Aprotinin; Phase III Clinical Trial; Ventilator-free days; Pulmonary Function; Inflammatory Biomarkers

Outcome Measures

Primary Outcomes (1)

• Ventilator-Free Days (VFD) in patients with moderate or severe ARDS

  Number of days a patient is free from invasive mechanical ventilation (DLVI) within 28 days after first dose. A patient is considered ventilator-free after two consecutive calendar days of unassisted breathing. This outcome will be used to assess the efficacy of inhaled aprotinin compared with placebo.

  From first dose up to Day 28

Secondary Outcomes (9)

• Number of participants with at least one treatment-emergent adverse event

  From first dose up to Day 180

• Proportion of patients who die from any cause within 28, 90, or 180 days after receiving first dose of study treatment.

  At Day 28, Day 90, and Day 180

• Number of days free from ICU or hospital

  From first dose up to Day 28

• Number of days on renal or vasoactive support within 28 days after first dose

  From first dose up to Day 28

• Sequential Organ Failure Assessment (SOFA) score

  From Day 1 up to Day 28

Study Arms (2)

Inhaled Aprotinin Group

EXPERIMENTAL

Patients in this Experimental Group will receive inhaled aprotinin as an adjunctive therapy to standard supportive care for ARDS. Treatment is administered four times daily for 6 consecutive days. All patients continue to receive standard supportive care according to local practice.

Drug: Aprotinin (inhaled)

Inhaled Placebo Group

PLACEBO COMPARATOR

Patients in this Control Group will receive inhaled placebo (sodium chloride) as an adjunctive therapy to standard supportive care for ARDS. Administration schedule matches the experimental group, four times daily for 6 consecutive days. All patients continue to receive standard supportive care according to local practice.

Drug: Placebo (Sodium Chloride)

Interventions

Aprotinin (inhaled) DRUG

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.

Inhaled Aprotinin Group

Placebo (Sodium Chloride) DRUG

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.

Inhaled Placebo Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Each potential participant must satisfy all of the following criteria to be enrolled in the study:
• Diagnosed with moderate or severe Acute Respiratory Distress Syndrome (ARDS) according to the Berlin definition (ARDS Definition Task Force 2012):
• Acute onset of respiratory failure within 1 week of a known clinical insult or new/worsening respiratory symptoms.
• Respiratory failure not fully explained by cardiac failure or fluid overload; objective evaluation of cardiac failure or fluid overload is required if ARDS risk factors are absent.
• Radiographic abnormalities on chest X-ray or CT scan: bilateral opacities not fully explained by effusions, nodules, masses, or lobar/segmental collapse.
• Hypoxemia:
• Moderate ARDS: PaO₂/FiO₂ \>100 mmHg and ≤200 mmHg with Positive End-Expiratory Pressure (PEEP) ≥5 cmH₂O.
• Severe ARDS: PaO₂/FiO₂ ≤100 mmHg with PEEP ≥5 cmH₂O.
• Radiographic and hypoxemia criteria must occur within the same 24-hour period. ARDS onset is defined as the time when the last of these two criteria is met.
• First dose of study drug planned within 48 hours of moderate or severe ARDS diagnosis.
• Intubated and receiving mechanical ventilation.
• Age ≥18 years.
• Women of childbearing potential must have a negative serum pregnancy test during screening and a negative urine pregnancy test at study start. Female subjects of childbearing potential and male subjects with partners of childbearing potential must agree to use an effective contraceptive method from consent until 30 days after study drug administration.

You may not qualify if:

• Any potential participant who meets any of the following criteria will be excluded from participating in the study:
• Pregnant or lactating women, or positive/indeterminate pregnancy test (serum or urine).
• Simultaneous participation in another pharmacotherapy protocol.
• Life expectancy \<24 hours.
• Clinical condition in which, in the investigator's opinion, ventilator withdrawal is extremely unlikely (e.g., motor neuron disease, Duchenne muscular dystrophy, rapidly progressive interstitial lung disease).
• Severe chronic obstructive pulmonary disease requiring long-term home oxygen or mechanical ventilation (noninvasive or tracheostomy), except Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP) used solely for sleep-related respiratory disorders.
• Congestive heart failure defined as New York Heart Association (NYHA) class IV.
• Acute left ventricular failure.
• Severe hepatic impairment (Child-Pugh class C).
• Prior interferon therapy.
• Known hypersensitivity to natural or recombinant IFN beta or any excipients.
• Receiving renal dialysisfor chronic renal failure.
• Receiving extracorporeal membrane oxygenation (ECMO), high-frequency oscillatory ventilation, or any form of extracorporeal pulmonary support.
• Mechanical ventilation, (invasive or noninvasive, excluding CPAP alone), for more than 48 hours before ARDS diagnosis. Noninvasive ventilation must be applied continuously for at least 12 hours/day during those 48 hours.
• Burns covering ≥15% total body surface.

Sponsors & Collaborators

• Fundacion del Hospital Nacional de Paraplejicos para la Investigacion y la Integracion: lead

Study Sites (1)

Hospital General Universitario de Ciudad Real

Ciudad Real, Ciudad Real, 13005, Spain

Location

MeSH Terms

Conditions

Respiratory Distress Syndrome

Interventions

Aprotinin; Inhalation; Sodium Chloride

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Proteins; Amino Acids, Peptides, and Proteins; Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

Francisco Javier Redondo Calvo, MD, PhD

CONTACT

+34 926 27 80 00; fjredondo@sescam.jccm.es

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase III, multicentre, double-blind, randomized, parallel-group clinical trial evaluating the efficacy and safety of inhaled aprotinin versus placebo in adult patients with moderate or severe ARDS.

Study Record Dates

• First Submitted: December 19, 2025
• First Posted: January 5, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2030
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)