Clinical trial NCT05254990: Reparixin add-on Therapy to Std Care to Limit Progression in Pts With COVID19 & Other Community Acquired Pneumonia
Official title: Reparixin 1200 mg TID as add-on to SoC to Limit Disease Progression in Hospitalised Patients With COVID-19 and Other Community-Acquired Pneumonia. A Multicentre, Randomised, Double-blinded, Placebo-controlled, Phase III Trial (REPAVID-22)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Infectious Pneumonia
Severe COVID-19
Keywords: COVID-19
SARS-CoV-2
Infectious pneumonia acquired in the community (CAP)
Lead sponsor: Dompé Farmaceutici S.p.A
Sponsor class: INDUSTRY
First posted: 2022-02-24
Enrollment: 409
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: male and female patients \>18 years, hospitalised for COVID-19, will be 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.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients dead or requiring Invasive Mechanical Ventilation (IMV) or Extracorporeal Membrane Oxygenation (ECMO) by day 28 [NIAID-OS 7].
timeFrame: Day 28
Secondary outcomes:
measure: All-cause mortality at day 180
timeFrame: Day 180
measure: Proportion of patients alive and discharged at day 28
timeFrame: Day 28
measure: Ventilatory-free days (VFD) at day 28
timeFrame: Day 28
measure: Occurrence of IMV (or ECMO) by day 28
timeFrame: Day 28
measure: Length of primary hospital stay
timeFrame: Throughout the trial
measure: Clinical failure by day 3 and day 7
timeFrame: day 3 and day 7
measure: 28-day ICU-free days
timeFrame: Day 28
measure: Days free of IMV/ECMO (number of days with NIAID-OS 1-6) at day 28
timeFrame: Day 28
measure: Duration of antibiotic therapy (days) at day 28
timeFrame: Day 28
measure: Hospital free days
timeFrame: Day 28
measure: Proportion of patients recovered
timeFrame: days 3, 7±1, 14±2, 21±2, 28 ±2 or at hospital discharge
measure: Proportion of patients worsening
timeFrame: days 3, 7±1, 14±2, 21±2, 28 ±2 or at hospital discharge
measure: PO2/FiO2
timeFrame: days 3, 7±1, 14±2, 21±2, 28 ±2 or at hospital discharge
measure: All-cause mortality
timeFrame: Days 28 and 90
measure: Hospital re-admission by day 90 and 180
timeFrame: Days 90 and 180
measure: Time to discharge or to a NEWS of ≤ 2 (for 24 hours), whichever occurs first
timeFrame: Day 28
measure: Change in inflammatory markers (LDH, CRP, ferritin; D-dimer, PCT) and cytokines
timeFrame: Days 3, 7±1, 14±2, 21±2, 28±2 or at hospital discharge]
measure: Change in quality of life using EuroQol-5-dimensions-5 levels (EQ-5D-5L) questionnaire
timeFrame: 90±7 and 180±14 days
measure: Duration of IMV and/or ECMO at 90 and 180 days
timeFrame: Days 90 and 180
measure: ICU admission at 90 and 180 days
timeFrame: Days 90 and 180
measure: ICU length of stay at 90 and 180 days
timeFrame: Days 90 and 180
measure: Hospital length of stay at 90 and 180 days
timeFrame: Days 90 and 180
measure: Occurrence of infections at 90 and 180 days
timeFrame: Days 90 and 180
Other outcomes:
Locations:
city: Tucson
country: United States
facility: MD Banner University Medical Center /Arizona University
state: Arizona
city: Davis
country: United States
facility: UC Davis Medical Center - UC Davis Medical Group - Davis
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Orange
country: United States
facility: UCI Health
state: California
city: Denver
country: United States
facility: Denver Health
state: Colorado
city: Danbury
country: United States
facility: Nuvance Health
state: Connecticut
city: Washington
country: United States
facility: MedStar Health Research Institute-Hyatteville, Maryland
state: District of Columbia
city: Clearwater
country: United States
facility: Research Alliance Inc.
state: Florida
city: Jacksonville
country: United States
facility: University of Florida-Jacksonville
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Emory Johns Creek Hospital
state: Georgia
city: Augusta
country: United States
facility: Augusta University Health - Augusta University Medical Center
state: Georgia
city: Chicago
country: United States
facility: Northwestern University, Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: Jesse Brown VA Medical Center
state: Illinois
city: Chicago
country: United States
facility: Insight Hospital & Medical Center Chicago
state: Illinois
city: Evanston
country: United States
facility: Northshore University HealthSystem
state: Illinois
city: Gary
country: United States
facility: Methodist Hospital
state: Indiana
city: Louisville
country: United States
facility: Norton Healthcare
state: Kentucky
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Newton
country: United States
facility: Newton-Wellesley Hospital
state: Massachusetts
city: Detroit
country: United States
facility: NorthStar Anesthesia / Detroit Medical Center
state: Michigan
city: Midland
country: United States
facility: MidMichigan Medical Center - Midland
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Columbia
country: United States
facility: University Hospital - MU Healthcare
state: Missouri
city: Saint Louis
country: United States
facility: Washington University, School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Research St Louis
state: Missouri
city: Brooklyn
country: United States
facility: NYU Langone Hospital-Brooklyn
state: New York
city: New York
country: United States
facility: New York University Langone Health
state: New York
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Oklahoma City
country: United States
facility: University of Oklahoma Medical Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University (OHSU) - Pulmonary Clinic
state: Oregon
city: Philadelphia
country: United States
facility: Jefferson University Hospital
state: Pennsylvania
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Beaumont
country: United States
facility: Baptist Hospitals of Southeast Texas
state: Texas
city: Denison
country: United States
facility: Texoma Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospitals & Clinics
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Health
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Bahia Blanca
country: Argentina
facility: Hospital Interzonal General de Agudos Dr Jose Penna
state: Buenos Aires
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: CEMIC
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
state: Buenos Aires
city: La Plata
country: Argentina
facility: Hospital Italiano de La Plata
state: Buenos Aires
city: La Plata
country: Argentina
facility: Instituto Medico Platense
state: Buenos Aires
city: Munro
country: Argentina
facility: Clinica Independencia
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Hospital Aleman
state: Ciudad Autonoma Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Sanatorio Finochietto
state: Ciudad Autonoma De Buenos Aires
city: Villa María
country: Argentina
facility: Sanatorio de la Cañada
state: Cordoba
city: Rosario
country: Argentina
facility: Sanatorio Britanico S.A.
state: Santa Fe
city: San Miguel de Tucuman
country: Argentina
facility: Clinica Mayo de Urgencias Medicas Cruz Blanca SRL
state: Tucuman
city: Buenos Aires
country: Argentina
facility: Sanatorio Agote
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Clinica Adventista Belgrano
city: Córdoba
country: Argentina
facility: Clinica Chutro
city: Córdoba
country: Argentina
facility: Nuevo Hospital San Roque
city: Córdoba
country: Argentina
facility: Sanatorio Privado de la Cañada - Cordoba
city: Córdoba
country: Argentina
facility: Sanatorio Privado Duarte Quiroz De Clinica Colombo SA
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Hospital Brisbane
state: Queensland
city: Southport
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Linz
country: Austria
facility: Kepler Universitatsklinikum Med Campus III
city: Linz
country: Austria
facility: KH der Barmherzigen Brüder Linz
city: Wien
country: Austria
facility: Medizinische Universitaet Wien, Medizinische Klinik I, Abteilung für Infektionskrankheiten und Tropenmedizin
city: Wien
country: Austria
facility: Klinik Favoriten (Sozialmedizinisches Zentrum Sued - Kaiser-Franz-Josef-Spital mit Gottfried von Preyer'schem Kinderspital)
city: Dachau
country: Germany
facility: Albeilung für Kardiologie und Pneumologie
state: Bavaria
city: Hannover
country: Germany
facility: Medizinische Hochschule
state: Niedersachsen
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus TU Dresden
state: Sachsen
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen
state: Südniedersachsen
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
state: Thueringen
city: Bari
country: Italy
facility: UOC Malattie dell'Apparato Respiratorio, Policlinico di Bari
city: Bergamo
country: Italy
facility: ASST - Ospedale Papa Giovanni XXIII - UOC Pneumologia
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria di Bologna - Ospedale Sant'Orsola
city: Catanzaro
country: Italy
facility: Campus Universitario "Salvatore Venuta", Complesso Clinico, Padiglione B, 8° livello, Pneumologia
city: Ferrara
country: Italy
facility: Azienda Ospedaliera Universitaria Arcispedale Sant'Anna
city: Genova
country: Italy
facility: University Of Genoa - Ospedale Policlinico IRCCS San Martino di Genova
city: Milano
country: Italy
facility: Fondazione Ca' Granda Policlinico Milano
city: Milan
country: Italy
facility: IRCCS Istituto Clinico Humanitas U.O. Medicina D'Urgenza
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele Centro di Ricerca Anestesia e Rianimazione
city: Milan
country: Italy
facility: ASST SANTI PAOLO E CARLO Ospedale San Paolo Struttura Complessa Malattie Infettive
city: Milan
country: Italy
facility: Università degli Studi di Milano-Ospedale "L.Sacco" Polo Universitario - ASST Fatebenefratelli Sacco
city: Milan
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda Dipartimento Malattie Infettive
city: Monza
country: Italy
facility: ASST-Monza Ospedale San Gerardo Malattie Infettive
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II.
city: Napoli
country: Italy
facility: Clinica Pneumologica "L. Vanvitelli" - Osp Monaldi
city: Napoli
country: Italy
facility: Università degli Studi della Campania "Luigi Vanvitelli"
city: Padova
country: Italy
facility: Università degli studi di Padova, Unità Malattie Respiratorie
city: Palermo
country: Italy
facility: AOUP "P.Giaccone" - UOC Pneumologia
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo - UOC Pneumologia, Dipartimento di Scienze Mediche e Malattie Infettive
city: Reggio Emilia
country: Italy
facility: Struttura semplice di terapia demi-intensiva respiratoria S.C. di pneumologia AO IRCCS Santa Maria Nuova
city: Ankara
country: Turkey
facility: Ankara City Hospital
city: Diyarbakır
country: Turkey
facility: Dicle University, Medical Faculty
city: Gaziantep
country: Turkey
facility: Gaziantep Universitesi Sahinbey Arastirma Ve Uygulama Hastanesi
city: Istanbul
country: Turkey
facility: Acibadem Atakent Hospital
city: İzmir
country: Turkey
facility: Dokuz Eylul University Faculty of Medicine
city: Kayseri
country: Turkey
facility: Kayseri State Hospital
city: Kocaeli
country: Turkey
facility: Kocaeli Universitesi Tip Fakultesi
city: Malatya
country: Turkey
facility: Inonu Uni.Med.Faculty
city: Trabzon
country: Turkey
facility: Karadeniz Tecnical Uni. Med. Fac.
Study officials:
affiliation: IRCCS Ospedale San Raffaele Centro di Ricerca Anestesia e Rianimazione
name: Giovanni Landoni, MD
role: PRINCIPAL_INVESTIGATOR
References: