Acute Respiratory Distress Syndrome MedDRA version: 21.1 Level: PT Classification code 10001052 Term: Acute respiratory distress syndrome System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Reparixin
Product Code: [DF 1681Y]
Pharmaceutical Form: Tablet
INN or Proposed INN: REPARIXIN
CAS Number: 266359-83-5
Current Sponsor code: DF 1681Y
Concentration unit: mg milligram(s)
C
Sponsors
DOMPé FARMACEUTICI S.P.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed Informed Consent, according to local guidelines and regulation 2. Adults ( > or =18 years old). 3. Mechanically ventilated (invasive) patients with PaO2/FIO2 ratio less than or equal to 200 in the presence of PEEP of > or = to 5 mmHg. 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. less than or equal to 48 hours from fulfilling above ARDS criteria. 7. less than or equal to 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 IMP dose and must agree to at least one of the following reliable methods of contraception: a. 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; b. A non-hormonal intrauterine device or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide from at least 2 months before the screening visit until 30 days after the last IMP dose; c. A male sexual partner who agrees to use a male condom with spermicide; d. A sterile sexual partner; e. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 46 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Severe chronic hepatic disease (as verified by relevant history, imaging if pre-existent and ChildPugh score 12-15). 2. Severe chronic renal dysfunction: eGFR (MDRD) 30% increase in vasopressors 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: a) Documented allergy 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. b) Lactase deficiency, galactosemia or glucose-galactose malabsorption. c) History of GI bleeding or perforation due to previous Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) therapy or recurrent peptic ulcer/haemorrhage 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To characterize the efficacy of reparixin in ameliorating lung injury and systemic inflammation and expediting clinical recovery and liberation from mechanical ventilation of adult patients with moderate to severe ARDS (PaO2/FIO2 ratio less than or equal to 200). Furthermore, to characterize the PK of reparixin in this group of severely ill patients as well as the effect of reparixin on systemic biomarkers linked to a hyper-inflammatory ARDS phenotype29-31. Safety objectives: To evaluate the safety of reparixin versus placebo in the specific clinical setting, including the effect on the incidence of secondary infections.;Secondary Objective: Not applicable;Primary end point(s): Primary endpoint: -Change in oxygenation index (OI) from baseline to day 7 of treatment. The OI is defined as: % mean airway pressure x FIO2/PaO2 -Ventilator free days (VFD) at day 28;Timepoint(s) of evaluation of this end point: baseline to day 7 of treatment at day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Change in OI from baseline to day 4 (±8h) -Acute lung injury score [composite of PaO2/FIO2 ratio, PEEP, lung compliance (plateau airway pressure minus PEEP/TV) and extent of pulmonary infiltrates] at 2(±8h), 3(±8h), 7±1, 14±2 days (if still intubated) -SOFA scores at 2(±8h), 3(±8h), 7±1, 14±2 days (if still intubated) -Ventilatory ratio (product of minute ventilation and PaCO2) at 2(±8h), 3(±8h), 7±1, 14±2 days (if still intubated) - Incidence of ECMO at day 14±2 - Use of vasoactive medications at day 14±2 - CXR assessment of pulmonary edema by “radiographic assessment of lung edema” (RALE) score at 2(±8h), 3(±8h), 7±1, 14±2 days - Percentage of patients achieving pressure support ventilation equal to 5 cm H20 with PEEP equal to 5 cm H20 for 2 hours (measure of weaning) by day 28±2 or hospital discharge - ICU-free days by day 28±2 or hospital discharge - Hospital-free days by day 28±2 or hospital discharge - Incidence of tracheostomies by day 28±2 or hospital discharge - Incidence of LTAC facility by day 28±2 or hospital discharge - All-cause mortality by day ±2or hospital discharge - All-cause mortality by day 60 - Change from baseline to day 3±8h, 7±1 and 14±2 in plasma levels of Il-6, IL-8, PAI-1, Plasma TNFr-1, ICAM-1 RAGE;Timepoint(s) of evaluation of this end point: Per protocol | — |
Countries
Germany, Italy, United States
Contacts
Public ContactClinical Trial Manager
Dompé farmaceutici s.p.a.
Outcome results
None listed