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, Randomized, Double-blinded, Placebo-controlled, Phase III Trial (REPAVID-22)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 414
- 试验地点
- 74
- 主要终点
- Proportion of Patients Dead or Requiring Invasive Mechanical Ventilation (IMV) or Extracorporeal Membrane Oxygenation (ECMO) by Day 28 [NIAID-OS 7].
研究概览
简要总结
Primary objective:
- To compare the efficacy of reparixin vs. placebo in the proportion of patients dead or requiring IMV (or ECMO) by Day 28.
Key secondary objectives:
- To compare the efficacy of reparixin vs placebo in all-cause mortality at day 180.
- To compare the efficacy of reparixin vs placebo in proportion of patients alive and discharged at day 28
- To compare the efficacy of reparixin vs placebo in ventilatory-free days at day 28.
- To compare the efficacy of reparixin vs placebo in proportion of patients with IMV (or ECMO) by day 28.
- To compare the efficacy of reparixin vs placebo in length of primary hospital stay.
Other efficacy objectives
- To compare the efficacy of reparixin vs placebo on several disease severity/progression measures including recovery, ventilatory free days and mortality.
Safety objectives:
- To evaluate safety and tolerability of oral reparixin versus placebo in the specific clinical setting.
详细描述
Multinational, multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III trial.
This study was conducted at 101 sites across 7 countries (Argentina, Australia, Austria, Germany, Italy, Turkey, and the United States [US]) that enrolled 414 male and female patients > 18 years of age, hospitalized for CAP (including COVID-19). Please note that of these 101 sites, only 74 had enrolled patients and, hence, have been reported on CT.gov.
The maximum study duration for a participant was 180 days, which included screening (day -1 or 1), treatment (up to day 21), and follow-up period (up to day 180).
Of the 414 patients enrolled, 409 (98.8%) were randomized 1:1 to receive investigational products (oral reparixin [N = 205] or matched placebo [N = 204], three times a day (TID), for up to 21 days. Randomization was stratified according to disease severity and site.
Actually, 394 participants (96.3%)(oral reparixin [N = 201] or matched placebo [N = 193]) received at least 1 dose of the investigational product and hence were included in the FAS population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
The appearance, including packaging and labelling, of the investigational product tablets (reparixin and placebo) were identical in appearance such that the actual treatment could not be identified.
The investigational product identity remained unknown to participants, site staff, CRO and Dompé personnel until after the study was completed and the database was unblinded (5 February 2025).
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent signed
- •Male and female ≥18 years old;
- •Patients hospitalized for clinically suspected CAP, defined as the occurrence of (within 48h from hospital admission):
- •at least 1 of the following signs/symptoms: dyspnea, cough, purulent sputum, crackles (rales) and/or rhonchi
- •body temperature > 38°C or <36°C (before or during admission) or leucocytosis (> local ULN)
- •new/increased pulmonary infiltrate(s) by chest imaging
- •Need for non-invasive supplemental oxygen (NIAID-OS 5-6);
- •SpO2 <92% at room air, or PaO2/FiO2 (or SpO2/FiO2) <300;
- •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:
- •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
- •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
- •A male sexual partner who agrees to use a male condom with spermicide
- •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.
排除标准
- •Treatment with IMV or ECMO (NIAID-OS 7);
- •Hepatic dysfunction: ALT or AST > 5 ULN; history of chronic hepatic disease (defined with Child-Pugh score B or C);
- •Renal dysfunction: estimated glomerular filtration rate (eGFR, MDRD) <50 mL/min/1.73 m2, or need for haemodialysis or hemofiltration;
- •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)
- •Treatment with prohibited medication within 5 half-lives, and inability to stop during treatment period;
- •Anticipated discharge from the hospital or transfer to another hospital within 72 hours of screening
- •History of:
- •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)
- •lactase deficiency, galactosemia or glucose-galactose malabsorption
- •gastrointestinal bleeding or perforation due to previous NSAIDs therapy or recurrent peptic ulcer/haemorrhage
- •allergy to reparixin or any component of the IMP formulation
- •Active bleeding or bleeding diathesis (excluding menses), prior intracranial haemorrhage
- •Participation in other interventional clinical trials
- •Clinical condition not compatible with oral administration of the study drug
- •positive or missing pregnancy test before first drug intake or day 1;
- •pregnant or lactating women;
- •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
- •Current hospital stay >72h
- •Complicated CAP-associated conditions, such as fungal pulmonary infection, tuberculosis infection, abscess, empyema, significant bilateral pleural effusion, massive pulmonary embolism
研究组 & 干预措施
Placebo + standard of care (SoC)
Placebo tablets are identical in appearance to the active formulation. Placebo was administered with the same treatment schedule.
干预措施: Placebo (Other)
Reparixin + standard of care (SoC)
Reparixin was 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 were administered maintaining an interval between doses of about 8 hours.
干预措施: Reparixin (Drug)
结局指标
主要结局
Proportion of Patients Dead or Requiring Invasive Mechanical Ventilation (IMV) or Extracorporeal Membrane Oxygenation (ECMO) by Day 28 [NIAID-OS 7].
时间窗: Day 28
The primary endpoint was based on NIAID-OS ordinal scale (National Institute of Allergy and Infectious Disease) with score OS 7 which means patients "hospitalized, on invasive mechanical ventilation or ECMO". The scores on this scale of Disease severity range from OS 1 (best outcome) to OS 8 (worst outcome). NIAID-OS (National Institute of Allergy and Infectious Disease Ordinal Scale) SCORE Descriptor: * OS 1 Not hospitalized, no limitations on activities; * OS 2 Not hospitalized, limitation on activities and/or requiring home O2; * OS 3 Hospitalized, no supplemental O2 - no longer requires ongoing medical care; * OS 4 Hospitalized, no supplemental O2 - requiring ongoing medical care; * OS 5 Hospitalized, requiring supplemental O2; * OS 6 Hospitalized, on non-invasive ventilation or high-flow oxygen devices; * OS 7 Hospitalized, on invasive mechanical ventilation or ECMO; * OS 8 Death;
次要结局
- Hospital Free Days(Day 28)
- All-cause Mortality by Day 180(Day 180)
- Proportion of Patients Alive and Discharged From the Hospital by Day 28(Day 28)
- Ventilatory-free Days (VFD) by Day 28(Day 28)
- Proportion of Patients With IMV (or ECMO) by Day 28(Day 28)
- Length of Primary Hospital Stay (in Days)(Day 180)
- Clinical Failure by Day 3 and Day 7(Day 3 and Day 7)
- 28-day ICU-free Days(Day 28)
- Days Free of IMV or ECMO (Number of Days With NIAID-OS 1-6) by Day 28(Day 28)
- Duration of Antibiotic Therapy (Days) by Day 28(Day 28)
- Proportion of Patients Recovered(days 3, 7, 14, 21, 28, and hospital discharge (Up to Day 41))
- Proportion of Patients Worsening(days 3, 7, 14, 21, 28, and hospital discharge (Up to Day 41))
- Change From Baseline in the Arterial Partial Pressure of Oxygen (PaO2)(days 3, 7, 14, 21, 28, and hospital discharge (Up to Day 41))
- Change From Baseline in Pulse Oximetry (SpO2)(days 3, 7, 14, 21, 28, and hospital discharge (Up to Day 41))
- Change From Baseline in Inspired Oxygen (FiO2) Levels(days 3, 7, 14, 21, 28, and hospital discharge (Up to Day 41))
- Change From Baseline in PaO2/FiO2 Ratio(days 3, 7, 14, 21, 28, and hospital discharge (Up to Day 41))
- Change From Baseline in SpO2/FiO2 Ratio(Days 3, 7, 14, 21, and 28)
- All-cause Mortality(Days 28, 60 and 90)
- Hospital Re-admission by Day 90 and 180(Days 90 and 180)
- Time to Discharge or to a NEWS (National Early Warning Score) of ≤ 2 (for 24 Hours), Whichever Occurs First(Day 28)
- Change in Quality of Life Using EuroQol-5-dimensions-5 Levels (EQ-5D-5L) Questionnaire From Hospital Discharge to Day 90 and Day 180(Days 90±7 and 180±14)
- Duration of IMV and/or ECMO by Days 90 and 180(Days 90 and 180)
- Proportion of Participants Requiring ICU Admission by Days 90 and 180(Days 90 and 180)
- ICU Length of Stay by Days 90 and 180(Days 90 and 180)
- Hospital Length of Stay by Days 90 and 180(Days 90 and 180)
- Occurrence of Infections by Days 90 and 180(Days 90 and 180)
- Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE)(Throughout the study till Day 180 (± 14) or end of treatment)