Add-on Reparixin in Adult Patients With ARDS
Purpose
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 evaluate the safety of reparixin vs. placebo in patients enrolled in the study.
Condition
- Acute Respiratory Distress Syndrome, Adult
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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. 7. ≤7 days from hospital admission. 8. 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. 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
- Moderate-severe chronic hepatic disease (as verified by relevant history, imaging, if pre-existent, and Child-Pugh score B-C). 2. Severe chronic renal dysfunction: eGFR (MDRD) < 30 mL/min/1.73m2 or End Stage Renal Disease on renal replacement therapy. 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. Evidence of anoxic brain injury 6. Currently receiving ECMO or high frequency oscillatory ventilation. 7. Anticipated extubation within 24 hours of enrollment. 8. Active malignancy (with the exception of non-melanotic skin cancers). 9. Hemodynamic instability (>30% increase in vasopressor in the last 6 hours or norepinephrine > 0.5 mcg/Kg/min). 10. Evidence of gastrointestinal (GI) dysmotility e.g., due to acute pancreatitis or immediate post-op state, as demonstrated by persistent gastric distention, enteral feeding intolerability and/or persistent gastric residuals >500 ml). 11. Anticipated discharge from the hospital or transfer to another hospital within 72 hours of screening. 12. 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). 13. History of: 1. Documented allergy/hypersensitivity to more than one medication belonging to the class of sulfonamides, such as sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib (hypersensitivity to sulphanilamide antibiotics alone, e.g., sulfamethoxazole does not qualify for exclusion), and to the study product and/or its excipients. 2. Lactase deficiency, galactosemia or glucose-galactose malabsorption. 3. History of GI bleeding or perforation due to previous Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) therapy or recurrent peptic ulcer/haemorrhage. 4. Hypersensitive to ibuprofen. 14. Active bleeding (excluding menses) or bleeding diathesis including patients on chronically high doses of NSAIDs. 15. Pregnant or lactating women. 16. 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.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Masking Description
- 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.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Reparixin + Standard of care |
Reparixin tablets 1200 mg TID (2 tablets x 600 mg TID) as add-on to the standard of care (SoC). |
|
|
Placebo Comparator Placebo + Standard of care |
Placebo tablets with the same schedule of reparixin, as add-on to the standard of care (SoC) |
|
Recruiting Locations
The University of Alabama at Birmingham Hospital
Birmingham, Alabama 35233
Birmingham, Alabama 35233
Contact:
Peter Morris, MD
Peter Morris, MD
More Details
- Status
- Recruiting
- Sponsor
- Dompé Farmaceutici S.p.A
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. 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).