Reparixin add-on Therapy to Std Care to Limit Progression in Pts With COVID19 & Other Community Acquired Pneumonia

NCT ID: NCT05254990

Last Updated: 2024-10-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

409 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-27

Study Completion Date

2024-09-27

Brief Summary

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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

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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.

Conditions

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Infectious Pneumonia Severe COVID-19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Reparixin + standard of care

Reparixin will be administered orally at the dose of 1200 mg (2 x 600 mg tablets) TID (6 tablets daily) for up to 21 days.

The three daily doses will be administered maintaining an interval between doses of about 8 hours.

Group Type EXPERIMENTAL

Reparixin

Intervention Type DRUG

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.

Placebo + standard of care

Placebo tablets are identical in appearance to the active formulation. Placebo will be administered with the same treatment schedule.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type OTHER

Other Intervention Names

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Repertaxin L-lysine salt Matched placebo

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Dompé Farmaceutici S.p.A

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Giovanni Landoni, MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS Ospedale San Raffaele Centro di Ricerca Anestesia e Rianimazione

Locations

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MD Banner University Medical Center /Arizona University

Tucson, Arizona, United States

Site Status

UC Davis Medical Center - UC Davis Medical Group - Davis

Davis, California, United States

Site Status

University of Southern California

Los Angeles, California, United States

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UCI Health

Orange, California, United States

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Denver Health

Denver, Colorado, United States

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Nuvance Health

Danbury, Connecticut, United States

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MedStar Health Research Institute-Hyatteville, Maryland

Washington D.C., District of Columbia, United States

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Research Alliance Inc.

Clearwater, Florida, United States

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University of Florida-Jacksonville

Jacksonville, Florida, United States

Site Status

University of South Florida

Tampa, Florida, United States

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Emory Johns Creek Hospital

Atlanta, Georgia, United States

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Augusta University Health - Augusta University Medical Center

Augusta, Georgia, United States

Site Status

Northwestern University, Feinberg School of Medicine

Chicago, Illinois, United States

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Jesse Brown VA Medical Center

Chicago, Illinois, United States

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Insight Hospital & Medical Center Chicago

Chicago, Illinois, United States

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Northshore University HealthSystem

Evanston, Illinois, United States

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Methodist Hospital

Gary, Indiana, United States

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Norton Healthcare

Louisville, Kentucky, United States

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Tufts Medical Center

Boston, Massachusetts, United States

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Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

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Newton-Wellesley Hospital

Newton, Massachusetts, United States

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NorthStar Anesthesia / Detroit Medical Center

Detroit, Michigan, United States

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MidMichigan Medical Center - Midland

Midland, Michigan, United States

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William Beaumont Hospital

Royal Oak, Michigan, United States

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University Hospital - MU Healthcare

Columbia, Missouri, United States

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Washington University, School of Medicine

St Louis, Missouri, United States

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Mercy Research St Louis

St Louis, Missouri, United States

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NYU Langone Hospital-Brooklyn

Brooklyn, New York, United States

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New York University Langone Health

New York, New York, United States

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Duke University Hospital

Durham, North Carolina, United States

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University of Oklahoma Medical Center

Oklahoma City, Oklahoma, United States

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Oregon Health & Science University (OHSU) - Pulmonary Clinic

Portland, Oregon, United States

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Jefferson University Hospital

Philadelphia, Pennsylvania, United States

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University of Tennessee Medical Center

Knoxville, Tennessee, United States

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Baptist Hospitals of Southeast Texas

Beaumont, Texas, United States

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Texoma Medical Center

Denison, Texas, United States

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University of Utah Hospitals & Clinics

Salt Lake City, Utah, United States

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University of Virginia Medical Center

Charlottesville, Virginia, United States

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Virginia Commonwealth University Health

Richmond, Virginia, United States

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Medical College of Wisconsin

Milwaukee, Wisconsin, United States

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Hospital Interzonal General de Agudos Dr Jose Penna

Bahía Blanca, Buenos Aires, Argentina

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CEMIC

Ciudad Autonoma Buenos Aires, Buenos Aires, Argentina

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Hospital Italiano de Buenos Aires

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

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Hospital Italiano de La Plata

La Plata, Buenos Aires, Argentina

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Instituto Medico Platense

La Plata, Buenos Aires, Argentina

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Clinica Independencia

Munro, Buenos Aires, Argentina

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Sanatorio Finochietto

Ciudad Autonoma de Buenos Aire, Buenos Aires F.D., Argentina

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Hospital Aleman

Buenos Aires, Ciudad Autonoma Buenos Aires, Argentina

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Sanatorio de la Cañada

Villa María, Córdoba Province, Argentina

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Sanatorio Britanico S.A.

Rosario, Santa Fe Province, Argentina

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Clinica Mayo de Urgencias Medicas Cruz Blanca SRL

San Miguel de Tucumán, Tucumán Province, Argentina

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Clinica Adventista Belgrano

Buenos Aires, , Argentina

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Sanatorio Agote

Buenos Aires, , Argentina

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Hospital Britanico de Buenos Aires

Ciudad Autonoma Buenos Aires, , Argentina

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Clinica Chutro

Córdoba, , Argentina

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Nuevo Hospital San Roque

Córdoba, , Argentina

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Sanatorio Privado de la Cañada - Cordoba

Córdoba, , Argentina

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Sanatorio Privado Duarte Quiroz De Clinica Colombo SA

Córdoba, , Argentina

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Westmead Hospital

Sydney, New South Wales, Australia

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Mater Hospital Brisbane

South Brisbane, Queensland, Australia

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Gold Coast University Hospital

Southport, Queensland, Australia

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Royal Adelaide Hospital

Adelaide, South Australia, Australia

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Royal Melbourne Hospital

Parkville, Victoria, Australia

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Kepler Universitatsklinikum Med Campus III

Linz, , Austria

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KH der Barmherzigen Brüder Linz

Linz, , Austria

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Medizinische Universitaet Wien, Medizinische Klinik I, Abteilung für Infektionskrankheiten und Tropenmedizin

Vienna, , Austria

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Klinik Favoriten (Sozialmedizinisches Zentrum Sued - Kaiser-Franz-Josef-Spital mit Gottfried von Preyer'schem Kinderspital)

Vienna, , Austria

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Albeilung für Kardiologie und Pneumologie

Dachau, Bavaria, Germany

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Medizinische Hochschule

Hanover, Lower Saxony, Germany

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Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, Saxony, Germany

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Universitätsmedizin Göttingen

Göttingen, Südniedersachsen, Germany

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Universitaetsklinikum Jena

Jena, Thuringia, Germany

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UOC Malattie dell'Apparato Respiratorio, Policlinico di Bari

Bari, , Italy

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ASST - Ospedale Papa Giovanni XXIII - UOC Pneumologia

Bergamo, , Italy

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Azienda Ospedaliera Universitaria di Bologna - Ospedale Sant'Orsola

Bologna, , Italy

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Campus Universitario "Salvatore Venuta", Complesso Clinico, Padiglione B, 8° livello, Pneumologia

Catanzaro, , Italy

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Azienda Ospedaliera Universitaria Arcispedale Sant'Anna

Ferrara, , Italy

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University Of Genoa - Ospedale Policlinico IRCCS San Martino di Genova

Genova, , Italy

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IRCCS Istituto Clinico Humanitas U.O. Medicina D'Urgenza

Milan, , Italy

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IRCCS Ospedale San Raffaele Centro di Ricerca Anestesia e Rianimazione

Milan, , Italy

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ASST SANTI PAOLO E CARLO Ospedale San Paolo Struttura Complessa Malattie Infettive

Milan, , Italy

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Università degli Studi di Milano-Ospedale "L.Sacco" Polo Universitario - ASST Fatebenefratelli Sacco

Milan, , Italy

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ASST Grande Ospedale Metropolitano Niguarda Dipartimento Malattie Infettive

Milan, , Italy

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Fondazione Ca' Granda Policlinico Milano

Milan, , Italy

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ASST-Monza Ospedale San Gerardo Malattie Infettive

Monza, , Italy

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Azienda Ospedaliera Universitaria Federico II.

Napoli, , Italy

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Clinica Pneumologica "L. Vanvitelli" - Osp Monaldi

Napoli, , Italy

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Università degli Studi della Campania "Luigi Vanvitelli"

Napoli, , Italy

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Università degli studi di Padova, Unità Malattie Respiratorie

Padua, , Italy

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AOUP "P.Giaccone" - UOC Pneumologia

Palermo, , Italy

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Fondazione IRCCS Policlinico San Matteo - UOC Pneumologia, Dipartimento di Scienze Mediche e Malattie Infettive

Pavia, , Italy

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Struttura semplice di terapia demi-intensiva respiratoria S.C. di pneumologia AO IRCCS Santa Maria Nuova

Reggio Emilia, , Italy

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Ankara City Hospital

Ankara, , Turkey (Türkiye)

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Dicle University, Medical Faculty

Diyarbakır, , Turkey (Türkiye)

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Gaziantep Universitesi Sahinbey Arastirma Ve Uygulama Hastanesi

Gaziantep, , Turkey (Türkiye)

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Acibadem Atakent Hospital

Istanbul, , Turkey (Türkiye)

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Dokuz Eylul University Faculty of Medicine

Izmir, , Turkey (Türkiye)

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Kayseri State Hospital

Kayseri, , Turkey (Türkiye)

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Kocaeli Universitesi Tip Fakultesi

Kocaeli, , Turkey (Türkiye)

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Inonu Uni.Med.Faculty

Malatya, , Turkey (Türkiye)

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Karadeniz Tecnical Uni. Med. Fac.

Trabzon, , Turkey (Türkiye)

Site Status

Countries

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United States Argentina Australia Austria Germany Italy Turkey (Türkiye)

References

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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)

Other Identifiers

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2021-006951-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

REP0321

Identifier Type: -

Identifier Source: org_study_id

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