Add-on Reparixin in Adult Patients With ARDS

NCT ID: NCT05496868

Last Updated: 2025-10-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-06
• Study Completion Date: 2025-04-18

Brief Summary

Study objectives

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. to assess the effect of reparixin on systemic biomarkers linked to a hyper-inflammatory ARDS phenotype.

3. To evaluate the safety of reparixin vs. placebo in patients enrolled in the study.

Detailed Description

Phase 2, randomized, double-blinded, placebo controlled, multicenter study. All patients will receive therapy in line with current standard-of-care as it pertains to ARDS management (protocolized ventilator management will be made available to all sites in accordance with currently accepted standard of care). Patients will be randomized (1:1) to either reparixin or placebo. Duration of treatment will be 14 days. In this study the IMP will be either reparixin or matched placebo, which will be provided in the form of tablets to be disintegrated for naso-gastric tube administration or administered orally after extubation and between extubation and day 14 should the patient be able to swallow. In such cases the IMP may be administered either intact or crushed and mixed with a vehicle as per speech swallow evaluation.

The study will consist of 4 study periods:

Screening Randomization and Baseline assessments, Treatment (14 days with discretionary extension up to 21 days), Follow-up (up to 28 days or hospital discharge, whichever occurs first, and then up to day-60).

Conditions

Acute Respiratory Distress Syndrome, Adult

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Reparixin + Standard of care

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

Group Type: EXPERIMENTAL

Reparixin 600mg

Intervention Type: 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

Placebo + Standard of care

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

Group Type: PLACEBO_COMPARATOR

Matching Placebo

Intervention Type: 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

Interventions

Reparixin 600mg

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

Intervention Type: DRUG

Matching Placebo

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

Intervention Type: OTHER

Other Intervention Names

REP; Control

Eligibility Criteria

Inclusion Criteria

1. Signed Informed Consent, according to local guidelines and regulation.

2. Male and female adults (>18 years old).

3. Mechanically ventilated (invasive) patients with PaO2/FIO2 ratio ≤200 in the presence of PEEP of ≥5 cmH20.

4. 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).

5. 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.

6. ≤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)

7. 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:

1. 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;

2. A sterile sexual partner;

3. 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.

Exclusion Criteria

1. 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

2. 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)

3. Participation in another interventional clinical trial.

4. Patients that are clinically determined to have a high likelihood of death within the next 24 hours based on PI's estimation.

5. Currently receiving ECMO or high frequency oscillatory ventilation.

6. Anticipated extubation within 24 hours of screening. (In such cases re-screening is allowed if the patient is within the enrollment window).

7. 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).

8. Anticipated transfer to a hospital not participating in the trial within 72 hours of screening.

9. 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).

10. History of:

1. Documented allergy/hypersensitivity to sulfonamides, ibuprofen and other COX-1 and 2 inhibitors, and to the study product and/or its excipients.

2. Lactase deficiency, galactosemia or glucose-galactose malabsorption.

3. History of peptic ulcer, GI bleeding or perforation due to previous NSAID therapy.

11. Active bleeding (excluding menses) from uncontrolled site that cannot be definitively resolved prior to enrollment.

12. Pregnant or lactating women.

13. Women of childbearing potential and fertile men who do not agree to use at least one primary form of contraception during the study and up to 30 days after the last IMP dose. For 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 he/she is able to do so.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dompé Farmaceutici S.p.A

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Moerer Onnen, MD

Role: PRINCIPAL_INVESTIGATOR

Universitaetsmedizin Goettingen

Locations

The University of Alabama at Birmingham Hospital

Birmingham, Alabama, United States

Banner - University Medical Center Phoenix

Phoenix, Arizona, United States

University of Southern California

Los Angeles, California, United States

University of California Irvine Health

Orange, California, United States

Unversity of California Davis Medical Center

Sacramento, California, United States

Denver Health

Denver, Colorado, United States

University of South Florida

Tampa, Florida, United States

Emory Saint Joseph's Hospital

Atlanta, Georgia, United States

Methodist Hospitals of Northwest Indiana

Gary, Indiana, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Newton Wellesley Hospital

Newton, Massachusetts, United States

Baystate Health

Springfield, Massachusetts, United States

Detroit Medical Center

Detroit, Michigan, United States

Henry Ford Hospital

Detroit, Michigan, United States

MyMichigan Medical Center Midland

Midland, Michigan, United States

William Beaumont Hospital

Royal Oak, Michigan, United States

Jackson Pulmonary Associates

Jackson, Mississippi, United States

University of Missouri Health Care

Columbia, Missouri, United States

Hackensack Meridian Health

Hackensack, New Jersey, United States

NYU Langone Brooklyn

Brooklyn, New York, United States

New York University Langone Health

New York, New York, United States

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

University of Oklahoma Medical Center

Oklahoma City, Oklahoma, United States

Oregon Health and Science University

Portland, Oregon, United States

University of Tennessee Medical Center

Knoxville, Tennessee, United States

Baptist Hospitals of Southeast Texas

Beaumont, Texas, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Cardiovoyage

Denison, Texas, United States

Houston Methodist Hospital

Houston, Texas, United States

University of Utah Hospitals & Clinics

Salt Lake City, Utah, United States

Virginia Commonwealth University Health System

Richmond, Virginia, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Universitaetsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Universitaetsmedizin Goettingen

Göttingen, Lower Saxony, Germany

Herzzentrum Muenster

Münster, North Rhine-Westphalia, Germany

Universitaetsklinikum Leipzig

Leipzig, Saxony, Germany

Berufsgenossenschaftliche Kliniken Bergmannstrost

Halle, Saxony-Anhalt, Germany

University Hospital of Schleswig-Holstein

Kiel, Schleswig-Holstein, Germany

Ospedale San Raffaele

Milan, Lombardy, Italy

Countries

United States; Germany; Italy

References

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.

Reference Type: DERIVED

PMID: 40028879 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2022-001612-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

REP0122

Identifier Type: -

Identifier Source: org_study_id