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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
409
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.
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.
MD Banner University Medical Center /Arizona University
Tucson, Arizona, United States
UC Davis Medical Center - UC Davis Medical Group - Davis
Davis, California, United States
University of Southern California
Los Angeles, California, United States
UCI Health
Orange, California, United States
Denver Health
Denver, Colorado, United States
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
Time frame: Day 28
All-cause mortality at day 180
Time frame: Day 180
Proportion of patients alive and discharged at day 28
Time frame: Day 28
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
Time frame: Day 28
Occurrence of IMV (or ECMO) by day 28
Time frame: Day 28
Length of primary hospital stay
Time frame: Throughout the trial
Clinical failure by day 3 and day 7
Clinical failure will be defined as the occurrence of IMV/ECMO or vasopressor, or death
Time frame: day 3 and day 7
28-day ICU-free days
Time frame: Day 28
Days free of IMV/ECMO (number of days with NIAID-OS 1-6) at day 28
Time frame: Day 28
Duration of antibiotic therapy (days) at day 28
Time frame: Day 28
Hospital free days
Time frame: Day 28
Proportion of patients recovered
downward shift from screening of ≤2 points on the NIAID-OS or live discharge from hospital)
Time frame: days 3, 7±1, 14±2, 21±2, 28 ±2 or at hospital discharge
Proportion of patients worsening
upward shift from screening of at least \>1 point of the NIAID-OS)
Time frame: days 3, 7±1, 14±2, 21±2, 28 ±2 or at hospital discharge
PO2/FiO2
Time frame: days 3, 7±1, 14±2, 21±2, 28 ±2 or at hospital discharge
All-cause mortality
Time frame: Days 28 and 90
Hospital re-admission by day 90 and 180
Time frame: Days 90 and 180
Time to discharge or to a NEWS of ≤ 2 (for 24 hours), whichever occurs first
Time frame: Day 28
Change in inflammatory markers (LDH, CRP, ferritin; D-dimer, PCT) and cytokines
Time frame: Days 3, 7±1, 14±2, 21±2, 28±2 or at hospital discharge]
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.
Time frame: 90±7 and 180±14 days
Duration of IMV and/or ECMO at 90 and 180 days
Time frame: Days 90 and 180
ICU admission at 90 and 180 days
Time frame: Days 90 and 180
ICU length of stay at 90 and 180 days
Time frame: Days 90 and 180
Hospital length of stay at 90 and 180 days
Time frame: Days 90 and 180
Occurrence of infections at 90 and 180 days
Time frame: Days 90 and 180
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Nuvance Health
Danbury, Connecticut, United States
MedStar Health Research Institute-Hyatteville, Maryland
Washington D.C., District of Columbia, United States
Research Alliance Inc.
Clearwater, Florida, United States
University of Florida-Jacksonville
Jacksonville, Florida, United States
University of South Florida
Tampa, Florida, United States
...and 91 more locations