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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05254990
Other study ID # REP0321
Secondary ID 2021-006951-32
Status Recruiting
Phase Phase 3
First received
Last updated
Start date April 6, 2022
Est. completion date October 2024

Study information

Verified date June 2024
Source Dompé Farmaceutici S.p.A
Contact Sophie Toya, MD
Phone +1 219 427 2474
Email sophie.toya@dompe.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Primary objective: - To evaluate the efficacy of oral reparixin versus standard care alone in limiting disease progression in adult patients hospitalised for infectious pneumonia acquired in the community (CAP), including COVID-19. Secondary objectives: - To determine the effect of reparixin on several disease severity/progression measures including recovery, ventilatory free days and mortality. Safety objectives: - To evaluate the safety of oral reparixin versus placebo in the specific clinical setting.


Description:

Multinational, multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase III trial. It will enrol 526 male and female patients >18 years, hospitalised for CAP (including COVID-19), assigned (1:1) to receive either oral reparixin (treatment group) or matched placebo (control group) three times a day (TID) for up to 21 days. Randomisation will be stratified according to disease severity and site. All the patients will receive the standard of care based on their clinical need, including COVID-19 and CAP medications, as per local standard therapy at the trial site and in line with international guidelines. The primary outcome will be evaluated at day 28, secondary will be evaluated from day 3 to day 180. An independent external data monitoring committee (DMC) will oversee the study and evaluate unblinded interim data for efficacy, futility, and safety.


Recruitment information / eligibility

Status Recruiting
Enrollment 526
Est. completion date October 2024
Est. primary completion date September 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Informed consent signed 2. Male and female =18 years old; 3. Patients hospitalized for clinically suspected CAP, defined as the occurrence of (within 48h from hospital admission): 1. at least 1 of the following signs/symptoms: dyspnea, cough, purulent sputum, crackles (rales) and/or rhonchi 2. body temperature > 38°C or <36°C (before or during admission) or leucocytosis (> local ULN) 3. new/increased pulmonary infiltrate(s) by chest imaging 4. Need for non-invasive supplemental oxygen (NIAID-OS 5-6; Appendix 14.4.1); 5. SpO2 <92% at room air, or PaO2/FiO2 (or SpO2/FiO2) <300; 6. Females of child-bearing potential and with an active sexual life must not wish to get pregnant within 30 days after the end of the study and must be using at least one of the following reliable methods of contraception: 1. Hormonal contraception, systemic, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit until 30 days after the last IMP dose 2. A non-hormonal intrauterine device [IUD] or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit until 30 days after the last IMP dose 3. A male sexual partner who agrees to use a male condom with spermicide 4. A sterile sexual partner 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. Treatment with IMV or ECMO (NIAID-OS 7); 2. Hepatic dysfunction: ALT or AST > 5 ULN; history of chronic hepatic disease (defined with Child-Pugh score B or C); 3. Renal dysfunction: estimated glomerular filtration rate (eGFR, MDRD) <50 mL/min/1.73 m2, or need for haemodialysis or hemofiltration; 4. Current use of >2 immunosuppressive medications or immunosuppression status (AIDS, aplastic anaemia, asplenia, systemic chemotherapy within the past 3 months, neutropenia (ANC < local LLN), solid organ or bone marrow transplant recipients) 5. Treatment with prohibited medication within 5 half-lives, and inability to stop during treatment period (see section 5.5.2); 6. Anticipated discharge from the hospital or transfer to another hospital within 72 hours of screening 7. History of: 1. intolerance or hypersensitivity to ibuprofen 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) 2. lactase deficiency, galactosemia or glucose-galactose malabsorption 3. gastrointestinal bleeding or perforation due to previous NSAIDs therapy or recurrent peptic ulcer/haemorrhage 4. allergy to reparixin or any component of the IMP formulation 8. Active bleeding or bleeding diathesis (excluding menses), prior intracranial haemorrhage 9. Participation in other interventional clinical trials 10. Clinical condition not compatible with oral administration of the study drug 11. Pregnancy: 1. positive or missing pregnancy test before first drug intake or day 1; 2. pregnant or lactating women; 3. women of childbearing potential and fertile men who do not agree to use at least one primary form of contraception for the duration of the study 12. Current hospital stay >72h 13. Complicated CAP-associated conditions, such as fungal pulmonary infection, tuberculosis infection, abscess, empyema, significant bilateral pleural effusion, massive pulmonary embolism

Study Design


Intervention

Drug:
Reparixin
Reparixin 600 mg tablets, administered orally at the dose of 1200 mg TID (2 tablets TID) as add-on therapy to standard of care up to 21 days. IMP can be taken with a glass of water (about 250 mL) and a light meal or snack, as it is preferable that reparixin is taken with food. However, if the patient is unable to eat, the study drug may still be administered without concomitant food ingestion.
Other:
Placebo
Administered orally three times a day (TID) as add-on therapy to standard of care up to 21 days. Placebo can be taken with a glass of water (about 250 mL) and a light meal or snack, as it is preferable that placebo is taken with food. However, if the patient is unable to eat, the placebo may still be administered without concomitant food ingestion.

Locations

Country Name City State
Argentina Hospital Interzonal General de Agudos Dr Jose Penna Bahia Blanca Buenos Aires
Argentina Hospital Aleman Buenos Aires Ciudad Autonoma Buenos Aires
Argentina Sanatorio Agote Buenos Aires
Argentina Hospital Cuenca Alta Nestor Kirchner Cañuelas Buenos Aires
Argentina CEMIC Ciudad Autonoma Buenos Aires Buenos Aires
Argentina Hospital Britanico de Buenos Aires Ciudad Autonoma Buenos Aires
Argentina Sanatorio Finochietto Ciudad Autonoma de Buenos Aire Ciudad Autonoma De Buenos Aires
Argentina Clinica Adventista Belgrano Ciudad Autonoma de Buenos Aires
Argentina Hospital General de Agudos Dr. J. M. Ramos Mejia Ciudad Autonoma de Buenos Aires
Argentina Hospital Italiano de Buenos Aires Ciudad Autonoma de Buenos Aires Buenos Aires
Argentina Hospital General de Agudos Dr. Ignacio Pirovano Ciudad de Buenos Aires Ciudad Autonoma Buenos Aires
Argentina Clinica Chutro Córdoba
Argentina Nuevo Hospital San Roque Córdoba
Argentina Sanatorio Allende Córdoba
Argentina Sanatorio Privado de la Cañada - Cordoba Córdoba
Argentina Sanatorio Privado Duarte Quiroz De Clinica Colombo SA Córdoba
Argentina Hospital Italiano de La Plata La Plata Buenos Aires
Argentina Instituto Medico Platense La Plata Buenos Aires
Argentina Clinica Independencia Munro Buenos Aires
Argentina Sanatorio Britanico S.A. Rosario Santa Fe
Argentina Clinica Mayo de Urgencias Medicas Cruz Blanca SRL San Miguel de Tucuman Tucuman
Argentina Sanatorio Parque S.A. Privado San Vicente Cordoba
Argentina Sanatorio de la Cañada Villa María Cordoba
Australia Royal Adelaide Hospital Adelaide South Australia
Australia Campbelltown Hospital Campbelltown New South Wales
Australia Royal Melbourne Hospital Parkville Victoria
Australia Mater Hospital Brisbane South Brisbane Queensland
Australia Gold Coast University Hospital Southport Queensland
Australia Westmead Hospital Sydney New South Wales
Austria Kepler Universitatsklinikum Med Campus III Linz
Austria KH der Barmherzigen Brüder Linz Linz
Austria Klinik Favoriten (Sozialmedizinisches Zentrum Sued - Kaiser-Franz-Josef-Spital mit Gottfried von Preyer'schem Kinderspital) Wien
Austria Medizinische Universitaet Wien, Medizinische Klinik I, Abteilung für Infektionskrankheiten und Tropenmedizin Wien
Germany Albeilung für Kardiologie und Pneumologie Dachau Bavaria
Germany Universitaetsklinikum Carl Gustav Carus TU Dresden Dresden Sachsen
Germany Universitätsmedizin Göttingen Göttingen Südniedersachsen
Germany Medizinische Hochschule Hannover Niedersachsen
Germany Universitaetsklinikum Jena Jena Thueringen
Italy UOC Malattie dell'Apparato Respiratorio, Policlinico di Bari Bari
Italy ASST - Ospedale Papa Giovanni XXIII - UOC Pneumologia Bergamo
Italy Azienda Ospedaliera Universitaria di Bologna - Ospedale Sant'Orsola Bologna
Italy Campus Universitario "Salvatore Venuta", Complesso Clinico, Padiglione B, 8° livello, Pneumologia Catanzaro
Italy University Of Genoa - Ospedale Policlinico IRCCS San Martino di Genova Genova
Italy ASST Grande Ospedale Metropolitano Niguarda Dipartimento Malattie Infettive Milan
Italy ASST SANTI PAOLO E CARLO Ospedale San Paolo Struttura Complessa Malattie Infettive Milan
Italy IRCCS Istituto Clinico Humanitas U.O. Medicina D'Urgenza Milan
Italy IRCCS Ospedale San Raffaele Centro di Ricerca Anestesia e Rianimazione Milan
Italy Università degli Studi di Milano-Ospedale "L.Sacco" Polo Universitario - ASST Fatebenefratelli Sacco Milan
Italy Fondazione Ca' Granda Policlinico Milano Milano
Italy ASST-Monza Ospedale San Gerardo Malattie Infettive Monza
Italy Clinica Pneumologica "L. Vanvitelli" - Osp Monaldi Napoli
Italy Università degli studi di Padova, Unità Malattie Respiratorie Padova
Italy AOUP "P.Giaccone" - UOC Pneumologia Palermo
Italy Fondazione IRCCS Policlinico San Matteo - UOC Pneumologia, Dipartimento di Scienze Mediche e Malattie Infettive Pavia
Italy Struttura semplice di terapia demi-intensiva respiratoria S.C. di pneumologia AO IRCCS Santa Maria Nuova Reggio Emilia
Turkey Ankara City Hospital Ankara
Turkey Dicle University, Medical Faculty Diyarbakir
Turkey Gaziantep Universitesi Sahinbey Arastirma Ve Uygulama Hastanesi Gaziantep
Turkey Acibadem Atakent Hospital Istanbul
Turkey Dokuz Eylul University Faculty of Medicine Izmir
Turkey Kayseri State Hospital Kayseri
Turkey Kocaeli Universitesi Tip Fakultesi Kocaeli
Turkey Inonu Uni.Med.Faculty Malatya
Turkey Karadeniz Tecnical Uni. Med. Fac. Trabzon
United States Emory Johns Creek Hospital Atlanta Georgia
United States Augusta University Health - Augusta University Medical Center Augusta Georgia
United States Baptist Hospitals of Southeast Texas Beaumont Texas
United States Beth Israel Deaconess Medical Center Boston Massachusetts
United States Tufts Medical Center Boston Massachusetts
United States NYU Langone Hospital-Brooklyn Brooklyn New York
United States University of Virginia Medical Center Charlottesville Virginia
United States Insight Hospital & Medical Center Chicago Chicago Illinois
United States Jesse Brown VA Medical Center Chicago Illinois
United States Northwestern University, Feinberg School of Medicine Chicago Illinois
United States Research Alliance Inc. Clearwater Florida
United States University Hospital - MU Healthcare Columbia Missouri
United States Nuvance Health Danbury Connecticut
United States UC Davis Medical Center - UC Davis Medical Group - Davis Davis California
United States Texoma Medical Center Denison Texas
United States Denver Health Denver Colorado
United States NorthStar Anesthesia / Detroit Medical Center Detroit Michigan
United States Duke University Hospital Durham North Carolina
United States Northshore University HealthSystem Evanston Illinois
United States Methodist Hospital Gary Indiana
United States Hackensack Meridian Health Hackensack New Jersey
United States University of Florida-Jacksonville Jacksonville Florida
United States University of Tennessee Medical Center Knoxville Tennessee
United States University of Southern California Los Angeles California
United States Norton Healthcare Louisville Kentucky
United States MidMichigan Medical Center - Midland Midland Michigan
United States Medical College of Wisconsin Milwaukee Wisconsin
United States New York University Langone Health New York New York
United States Newton-Wellesley Hospital Newton Massachusetts
United States University of Oklahoma Medical Center Oklahoma City Oklahoma
United States UCI Health Orange California
United States Jefferson University Hospital Philadelphia Pennsylvania
United States UPMC Presbyterian Pittsburgh Pennsylvania
United States Oregon Health & Science University (OHSU) - Pulmonary Clinic Portland Oregon
United States Virginia Commonwealth University Health Richmond Virginia
United States William Beaumont Hospital Royal Oak Michigan
United States Mercy Research St Louis Saint Louis Missouri
United States Washington University, School of Medicine Saint Louis Missouri
United States University of Utah Hospitals & Clinics Salt Lake City Utah
United States University of South Florida Tampa Florida
United States MD Banner University Medical Center /Arizona University Tucson Arizona
United States MedStar Health Research Institute-Hyatteville, Maryland Washington District of Columbia

Sponsors (1)

Lead Sponsor Collaborator
Dompé Farmaceutici S.p.A

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Germany,  Italy,  Turkey, 

Outcome

Type Measure Description Time frame Safety issue
Primary Proportion of patients dead or requiring Invasive Mechanical Ventilation (IMV) or Extracorporeal Membrane Oxygenation (ECMO) by day 28 [NIAID-OS 7]. NIAID-OS = National Institute of Allergy and Infectious Disease - Ordinal Scale Day 28
Secondary All-cause mortality at day 180 Day 180
Secondary Proportion of patients alive and discharged at day 28 Day 28
Secondary Ventilatory-free days (VFD) at day 28 Number of days from Day 0 to Day 28 when the patient will alive and free of invasive ventilation. In case of multiple periods of IMV during the first 28 days, the total duration of ventilation considered all periods of ventilation during the index admission. Patients who will die within 28 days or will be still on invasive ventilation after 28 days will score zero VFDs18 Day 28
Secondary Occurrence of IMV (or ECMO) by day 28 Day 28
Secondary Length of primary hospital stay Throughout the trial
Secondary Clinical failure by day 3 and day 7 Clinical failure will be defined as the occurrence of IMV/ECMO or vasopressor, or death day 3 and day 7
Secondary 28-day ICU-free days Day 28
Secondary Days free of IMV/ECMO (number of days with NIAID-OS 1-6) at day 28 Day 28
Secondary Duration of antibiotic therapy (days) at day 28 Day 28
Secondary Hospital free days Day 28
Secondary Proportion of patients recovered downward shift from screening of =2 points on the NIAID-OS or live discharge from hospital) days 3, 7±1, 14±2, 21±2, 28 ±2 or at hospital discharge
Secondary Proportion of patients worsening upward shift from screening of at least >1 point of the NIAID-OS) days 3, 7±1, 14±2, 21±2, 28 ±2 or at hospital discharge
Secondary PO2/FiO2 days 3, 7±1, 14±2, 21±2, 28 ±2 or at hospital discharge
Secondary All-cause mortality Days 28 and 90
Secondary Hospital re-admission by day 90 and 180 Days 90 and 180
Secondary Time to discharge or to a NEWS of = 2 (for 24 hours), whichever occurs first Day 28
Secondary Change in inflammatory markers (LDH, CRP, ferritin; D-dimer, PCT) and cytokines Days 3, 7±1, 14±2, 21±2, 28±2 or at hospital discharge]
Secondary Change in quality of life using EuroQol-5-dimensions-5 levels (EQ-5D-5L) questionnaire The EQ-5D-5L asks patients to indicate whether they have no, slight, moderate, severe, extreme problems on each of five dimensions of health: mobility; self-care; usual activities; pain/discomfort; anxiety/depression. 90±7 and 180±14 days
Secondary Duration of IMV and/or ECMO at 90 and 180 days Days 90 and 180
Secondary ICU admission at 90 and 180 days Days 90 and 180
Secondary ICU length of stay at 90 and 180 days Days 90 and 180
Secondary Hospital length of stay at 90 and 180 days Days 90 and 180
Secondary Occurrence of infections at 90 and 180 days Days 90 and 180
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