Add-on Reparixin in Adult Patients With ARDS

NCT05496868 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: REP01222022-001612-25
• Study Type: interventional
• Target: 66
• Locations: 3 countries
• Sites: 40

Brief Summary

Study objectives

1. 1.To characterize the efficacy of reparixin in ameliorating lung injury and systemic inflammation and expediting clinical recovery and liberation from mechanical ventilation in adult patients with moderate to severe ARDS (PaO2/FIO2 ratio ≤ 200).
2. 2.to assess the effect of reparixin on systemic biomarkers linked to a hyper-inflammatory ARDS phenotype.
3. 3.To evaluate the safety of reparixin vs. placebo in patients enrolled in the study.

Conditions

Acute Respiratory Distress Syndrome, Adult

Keywords

ARDS; Reparixin

Outcome Measures

Primary Outcomes (2)

• Change in Oxygenation Index (OI) From Baseline to Day 7 of Treatment

  Oxygenation Index is defined as Mean Airway Pressure multiplied by (Fraction of Inspired Oxygen\[FiO2\]) x (100)/(Partial Pressure of Oxygen\[PaO2\]). It is a measure of efficiency of oxygen utilization in the body, with lower values indicating better oxygenation. OI values can range from 0 to 1000, with values below 25 generally associated with more favorable clinical outcomes. OI at Day 7 was derived according to estimand definition. If a participant died before or at Day 7 and OI was missing, an unfavorable value was imputed. If a participant was extubated at Day 7 and OI was not evaluable, a favorable value was imputed. In all other cases, OI at Day 7 was considered missing. Baseline was defined as last measurement collected prior to investigational medicinal product intake. Change from baseline was defined as post-baseline assessment minus baseline value. Adjusted means and 95% confidence interval from an ANOVA model with multiple imputation (MI) for missing data have been presented.

  Baseline to Day 7

• Ventilator-Free Days (VFD)

  Ventilator free days (VFDs) through Day 28 were defined as the number of days from the first IMP intake during which the participant was alive and free of invasive mechanical ventilation. Participants who died before or at Day 28 were assigned a value of 0 ventilator-free days, in accordance with the estimand definition. Adjusted means and 95% confidence interval from an ANOVA model with MI for missing data have been presented.

  At Day 28

Secondary Outcomes (17)

• Change in Oxygenation Index (OI) From Baseline to Day 4

  Baseline to Day 4

• Change From Baseline of Acute Lung Injury (ALI) Score

  Baseline and at Days 2, 3, 7 and 14

• Change From Baseline of Sequential Organ Failure Assessment (SOFA) Score

  Baseline and at Days 2, 3, 7 and 14

• Change From Baseline of Ventilatory Ratio

  Baseline and at Days 2, 3, 7 and 14

• Number of Participants Requiring Extracorporeal Membrane Oxygenation (ECMO) at Day 14

  At Day 14

Study Arms (2)

Reparixin + Standard of care

EXPERIMENTAL

Reparixin tablets 1200 mg TID (2 tablets x 600 mg TID) as add-on to the standard of care (SoC).

Drug: Reparixin 600mg

Placebo + Standard of care

PLACEBO COMPARATOR

Placebo tablets with the same schedule of reparixin, as add-on to the standard of care (SoC)

Other: Matching Placebo

Interventions

Reparixin 600mg DRUG

Reparixin 600 mg tablets, administered crushed through nasogastric tube at the dose of 1200 mg TID (2 tablets TID administered approximately about every 8 hours) as add-on to the standard of care. After extubation and if the patient can swallow, reparixin may be administered orally. Total duration of the treatment: 14 days

Also known as: REP

Reparixin + Standard of care

Matching Placebo OTHER

Placebo tablets. Administered crushed through nasogastric tube with the same schedule as reparixin as add-on to the standard of care. After extubation and if the patient can swallow placebo may be administered orally. Total duration of the treatment: 14 days

Also known as: Control

Placebo + Standard of care

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent, according to local guidelines and regulation.
• Male and female adults (\>18 years old).
• Mechanically ventilated (invasive) patients with PaO2/FIO2 ratio ≤200 in the presence of PEEP of ≥5 cmH20.
• Respiratory failure not fully explained by cardiac failure or fluid overload (if acute Congestive Heart Failure exacerbation is identified as part of the clinical picture this should be addressed effectively and as soon as possible before the patient can be enrolled).
• Bilateral radiologic opacities consistent with pulmonary edema on the frontal chest x-ray (CXR), or bilateral ground glass opacities on a chest computerized tomography (CT) scan.
• ≤48 hours from fulfilling above ARDS criteria (if a patient is transferred from a non-participating hospital to a participating site a 12-hour period beyond the 48 hours is allowed)
• Females of child-bearing potential who are sexually active must be willing not to get pregnant within 30 days after the last Investigational Medicinal Product (IMP) dose and must agree to at least one of the following reliable methods of contraception:
• Hormonal contraception, systemic, implantable, transdermal, or injectable contraceptives from at least 2 months before the screening visit until 30 days after the last IMP dose;
• A sterile sexual partner;
• Abstinence. In patients non able to personally consent to above due to complications of acute illness and/or its treatment assurances for the above must be given by LR and reiterated by patient when/if she is able to do so.
• Female participants of non-child-bearing potential or in post- menopausal status for at least 1 year will be admitted. For all female subjects with child-bearing potential, pregnancy test result must be negative before first drug intake.

You may not qualify if:

• Moderate-Severe chronic hepatic disease (as verified by a previously known Child-Pugh score ≥7). If baseline Child-Pugh score is not known it should not be calculated while the patient is acutely ill. In that case the patient is excluded on the basis of: ALT/AST ≥ 3x ULN and total bilirubin \> 2x ULN or ALT/AST ≥ 5x ULN
• Severe chronic renal dysfunction: eGFR (2021 CKD-EPI) \< 30 mL/min/1.73m2. If baseline (chronic) renal function is not known the patient is only excluded if in need of acute renal replacement therapy (currently on RRT or to be imminently placed on RRT)
• Participation in another interventional clinical trial.
• Patients that are clinically determined to have a high likelihood of death within the next 24 hours based on PI's estimation.
• Currently receiving ECMO or high frequency oscillatory ventilation.
• Anticipated extubation within 24 hours of screening. (In such cases re-screening is allowed if the patient is within the enrollment window).
• Evidence of GI dysmotility as demonstrated by presence of all the following: persistent gastric distention and enteral feeding intolerability and persistent gastric residuals \>500 ml).
• Anticipated transfer to a hospital not participating in the trial within 72 hours of screening.
• Decision to withhold or withdraw life-sustaining treatment (patients may still be eligible however if they are committed to full support except cardiopulmonary resuscitation if cardiac arrest occurs).
• History of:
• Documented allergy/hypersensitivity to sulfonamides, ibuprofen and other COX-1 and 2 inhibitors, and to the study product and/or its excipients.
• Lactase deficiency, galactosemia or glucose-galactose malabsorption.
• History of peptic ulcer, GI bleeding or perforation due to previous NSAID therapy.
• Active bleeding (excluding menses) from uncontrolled site that cannot be definitively resolved prior to enrollment.
• Pregnant or lactating women.

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead

Study Sites (40)

The University of Alabama at Birmingham Hospital

Birmingham, Alabama, 35233, United States

Location

Banner - University Medical Center Phoenix

Phoenix, Arizona, 85006, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

University of California Irvine Health

Orange, California, 92868, United States

Location

Unversity of California Davis Medical Center

Sacramento, California, 95817, United States

Location

Denver Health

Denver, Colorado, 80204, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

Location

Methodist Hospitals of Northwest Indiana

Gary, Indiana, 46404, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Newton Wellesley Hospital

Newton, Massachusetts, 02462-1607, United States

Location

Baystate Health

Springfield, Massachusetts, 01107, United States

Location

Detroit Medical Center

Detroit, Michigan, 48201, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

MyMichigan Medical Center Midland

Midland, Michigan, 48670, United States

Location

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

Jackson Pulmonary Associates

Jackson, Mississippi, 39202, United States

Location

University of Missouri Health Care

Columbia, Missouri, 65212, United States

Location

Hackensack Meridian Health

Hackensack, New Jersey, 07601, United States

Location

NYU Langone Brooklyn

Brooklyn, New York, 11220, United States

Location

New York University Langone Health

New York, New York, 10016, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

University of Oklahoma Medical Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

Location

Baptist Hospitals of Southeast Texas

Beaumont, Texas, 77701, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390-8894, United States

Location

Cardiovoyage

Denison, Texas, 75020, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

University of Utah Hospitals & Clinics

Salt Lake City, Utah, 84108, United States

Location

Virginia Commonwealth University Health System

Richmond, Virginia, 23298, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Universitaetsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Universitaetsmedizin Goettingen

Göttingen, Lower Saxony, 37075, Germany

Location

Herzzentrum Muenster

Münster, North Rhine-Westphalia, 48149, Germany

Location

Universitaetsklinikum Leipzig

Leipzig, Saxony, 4103, Germany

Location

Berufsgenossenschaftliche Kliniken Bergmannstrost

Halle, Saxony-Anhalt, 6112, Germany

Location

University Hospital of Schleswig-Holstein

Kiel, Schleswig-Holstein, 24105, Germany

Location

Ospedale San Raffaele

Milan, Lombardy, 20132, Italy

Location

Related Publications (1)

• Truwit JD, Fleming K, Nanchal RS. Empowering Respiratory Therapists to Restrict Nebulized 3% Saline and N-Acetylcysteine During Mechanical Ventilation. Respir Care. 2025 Aug;70(8):937-945. doi: 10.1089/respcare.12586. Epub 2025 Feb 24.

  PMID: 40028879 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome

Interventions

reparixin

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Results Point of Contact

• Title: Clinical Development & Operations
• Organization: Dompé Farmaceutici S.p.A.

clinicaltrials@dompe.com

+39 02 583831

Study Officials

• Moerer Onnen, MD

  Universitaetsmedizin Goettingen

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: the identity of the treatments will remain unknown to the subject, Investigator, site staff, CRO and Dompé's personnel until the study completion and formal unmasking. Only the Data Monitoring Committee (DMC) will have access to group-unblinded and/or fully unblinded DMC reports.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2022
• First Posted: August 11, 2022
• Study Start: December 6, 2022
• Primary Completion: March 18, 2025
• Study Completion: April 18, 2025
• Last Updated: May 11, 2026
• Results First Posted: May 11, 2026

Record last verified: 2026-05

Locations

DE (6); IT (1); US (33)