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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05254990




Registration number
NCT05254990
Ethics application status
Date submitted
22/02/2022
Date registered
24/02/2022
Date last updated
24/10/2024

Titles & IDs
Public title
Reparixin add-on Therapy to Std Care to Limit Progression in Pts With COVID19 & Other Community Acquired Pneumonia
Scientific 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)
Secondary ID [1] 0 0
2021-006951-32
Secondary ID [2] 0 0
REP0321
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infectious Pneumonia 0 0
Severe COVID-19 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Sexually transmitted infections

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Reparixin
Other interventions - Placebo

Experimental: 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.

Placebo comparator: Placebo + standard of care - Placebo tablets are identical in appearance to the active formulation. Placebo will be administered with the same treatment schedule.


Treatment: Drugs: 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 interventions: 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 code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of patients dead or requiring Invasive Mechanical Ventilation (IMV) or Extracorporeal Membrane Oxygenation (ECMO) by day 28 [NIAID-OS 7].
Timepoint [1] 0 0
Day 28
Secondary outcome [1] 0 0
All-cause mortality at day 180
Timepoint [1] 0 0
Day 180
Secondary outcome [2] 0 0
Proportion of patients alive and discharged at day 28
Timepoint [2] 0 0
Day 28
Secondary outcome [3] 0 0
Ventilatory-free days (VFD) at day 28
Timepoint [3] 0 0
Day 28
Secondary outcome [4] 0 0
Occurrence of IMV (or ECMO) by day 28
Timepoint [4] 0 0
Day 28
Secondary outcome [5] 0 0
Length of primary hospital stay
Timepoint [5] 0 0
Throughout the trial
Secondary outcome [6] 0 0
Clinical failure by day 3 and day 7
Timepoint [6] 0 0
day 3 and day 7
Secondary outcome [7] 0 0
28-day ICU-free days
Timepoint [7] 0 0
Day 28
Secondary outcome [8] 0 0
Days free of IMV/ECMO (number of days with NIAID-OS 1-6) at day 28
Timepoint [8] 0 0
Day 28
Secondary outcome [9] 0 0
Duration of antibiotic therapy (days) at day 28
Timepoint [9] 0 0
Day 28
Secondary outcome [10] 0 0
Hospital free days
Timepoint [10] 0 0
Day 28
Secondary outcome [11] 0 0
Proportion of patients recovered
Timepoint [11] 0 0
days 3, 7±1, 14±2, 21±2, 28 ±2 or at hospital discharge
Secondary outcome [12] 0 0
Proportion of patients worsening
Timepoint [12] 0 0
days 3, 7±1, 14±2, 21±2, 28 ±2 or at hospital discharge
Secondary outcome [13] 0 0
PO2/FiO2
Timepoint [13] 0 0
days 3, 7±1, 14±2, 21±2, 28 ±2 or at hospital discharge
Secondary outcome [14] 0 0
All-cause mortality
Timepoint [14] 0 0
Days 28 and 90
Secondary outcome [15] 0 0
Hospital re-admission by day 90 and 180
Timepoint [15] 0 0
Days 90 and 180
Secondary outcome [16] 0 0
Time to discharge or to a NEWS of = 2 (for 24 hours), whichever occurs first
Timepoint [16] 0 0
Day 28
Secondary outcome [17] 0 0
Change in inflammatory markers (LDH, CRP, ferritin; D-dimer, PCT) and cytokines
Timepoint [17] 0 0
Days 3, 7±1, 14±2, 21±2, 28±2 or at hospital discharge]
Secondary outcome [18] 0 0
Change in quality of life using EuroQol-5-dimensions-5 levels (EQ-5D-5L) questionnaire
Timepoint [18] 0 0
90±7 and 180±14 days
Secondary outcome [19] 0 0
Duration of IMV and/or ECMO at 90 and 180 days
Timepoint [19] 0 0
Days 90 and 180
Secondary outcome [20] 0 0
ICU admission at 90 and 180 days
Timepoint [20] 0 0
Days 90 and 180
Secondary outcome [21] 0 0
ICU length of stay at 90 and 180 days
Timepoint [21] 0 0
Days 90 and 180
Secondary outcome [22] 0 0
Hospital length of stay at 90 and 180 days
Timepoint [22] 0 0
Days 90 and 180
Secondary outcome [23] 0 0
Occurrence of infections at 90 and 180 days
Timepoint [23] 0 0
Days 90 and 180

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/04/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/09/2024
Sample size
Target
Accrual to date
Final
409
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Westmead Hospital - Sydney
Recruitment hospital [2] 0 0
Mater Hospital Brisbane - South Brisbane
Recruitment hospital [3] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [4] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2145 - Sydney
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
4215 - Southport
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Kentucky
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Oklahoma
Country [17] 0 0
United States of America
State/province [17] 0 0
Oregon
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Utah
Country [22] 0 0
United States of America
State/province [22] 0 0
Virginia
Country [23] 0 0
United States of America
State/province [23] 0 0
Wisconsin
Country [24] 0 0
Argentina
State/province [24] 0 0
Buenos Aires
Country [25] 0 0
Argentina
State/province [25] 0 0
Ciudad Autonoma Buenos Aires
Country [26] 0 0
Argentina
State/province [26] 0 0
Ciudad Autonoma De Buenos Aires
Country [27] 0 0
Argentina
State/province [27] 0 0
Cordoba
Country [28] 0 0
Argentina
State/province [28] 0 0
Santa Fe
Country [29] 0 0
Argentina
State/province [29] 0 0
Tucuman
Country [30] 0 0
Argentina
State/province [30] 0 0
Ciudad Autonoma de Buenos Aires
Country [31] 0 0
Argentina
State/province [31] 0 0
Córdoba
Country [32] 0 0
Austria
State/province [32] 0 0
Linz
Country [33] 0 0
Austria
State/province [33] 0 0
Wien
Country [34] 0 0
Germany
State/province [34] 0 0
Bavaria
Country [35] 0 0
Germany
State/province [35] 0 0
Niedersachsen
Country [36] 0 0
Germany
State/province [36] 0 0
Sachsen
Country [37] 0 0
Germany
State/province [37] 0 0
Südniedersachsen
Country [38] 0 0
Germany
State/province [38] 0 0
Thueringen
Country [39] 0 0
Italy
State/province [39] 0 0
Bari
Country [40] 0 0
Italy
State/province [40] 0 0
Bergamo
Country [41] 0 0
Italy
State/province [41] 0 0
Bologna
Country [42] 0 0
Italy
State/province [42] 0 0
Catanzaro
Country [43] 0 0
Italy
State/province [43] 0 0
Ferrara
Country [44] 0 0
Italy
State/province [44] 0 0
Genova
Country [45] 0 0
Italy
State/province [45] 0 0
Milano
Country [46] 0 0
Italy
State/province [46] 0 0
Milan
Country [47] 0 0
Italy
State/province [47] 0 0
Monza
Country [48] 0 0
Italy
State/province [48] 0 0
Napoli
Country [49] 0 0
Italy
State/province [49] 0 0
Padova
Country [50] 0 0
Italy
State/province [50] 0 0
Palermo
Country [51] 0 0
Italy
State/province [51] 0 0
Pavia
Country [52] 0 0
Italy
State/province [52] 0 0
Reggio Emilia
Country [53] 0 0
Turkey
State/province [53] 0 0
Ankara
Country [54] 0 0
Turkey
State/province [54] 0 0
Diyarbakir
Country [55] 0 0
Turkey
State/province [55] 0 0
Gaziantep
Country [56] 0 0
Turkey
State/province [56] 0 0
Istanbul
Country [57] 0 0
Turkey
State/province [57] 0 0
Izmir
Country [58] 0 0
Turkey
State/province [58] 0 0
Kayseri
Country [59] 0 0
Turkey
State/province [59] 0 0
Kocaeli
Country [60] 0 0
Turkey
State/province [60] 0 0
Malatya
Country [61] 0 0
Turkey
State/province [61] 0 0
Trabzon

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Dompé Farmaceutici S.p.A
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT05254990
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Giovanni Landoni, MD
Address 0 0
IRCCS Ospedale San Raffaele Centro di Ricerca Anestesia e Rianimazione
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Sophie Toya, MD
Address 0 0
Country 0 0
Phone 0 0
+1 219 427 2474
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05254990