A Phase 3, Double-blind, Randomized, Placebo-controlled, Multicenter Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients With Severe COVID-19 Pneumonia
Overview
- Phase
- Phase 3
- Intervention
- Reparixin
- Conditions
- Pneumonia, Viral
- Sponsor
- Dompé Farmaceutici S.p.A
- Enrollment
- 287
- Locations
- 17
- Primary Endpoint
- Proportion of Patients Alive and Free of Respiratory Failure at Day 28
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The study objective is to assess Efficacy and safety of Reparixin treatment as compared to placebo (both on top of standard treatment) in adult patients with severe COVID-19 pneumonia.
Detailed Description
This is a phase 3 clinical trial designed as a randomized, double-blind, placebo-controlled, multicentre study to evaluate the efficacy and safety of Reparixin in hospitalized adult patients with severe COVID-19 pneumonia. Patients will be screened for the participation in the study and eventually randomized based on an unbalanced randomization scheme (2:1) to Reparixin oral tablets (2 x 600 mg TID) for up to 21 days or to placebo. An unequal randomization is justified by the need to gain experience and more safety data with the investigated treatment and by an expected better acceptability of the trial by patients. The placebo control arm is justified by the unavailability of a well-defined standard of care for subjects with COVID-19 pneumonia who are candidates for this study. All patient will receive the standard supportive care based on the patient's clinical need. Follow-up information on the patient's clinical condition will be collected until day 90.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 18 to 90, male and female subject of any race
- •Reverse transcriptase Polymerase Chain Reaction (rt-PCR)-confirmed COVID-19 infection based on a nasal / oropharyngeal swab within 10 days before randomization
- •At least one of the following: 1) Respiratory distress with tachypnea (RR ≥ 24 breaths/min without oxygen); 2) Partial arterial oxygen pressure (PaO2) / Fraction of inspiration O2 (FiO2), P/F \>100 and \<300 mmHg (1mmHg = 0.133kPa), 3) SpO2 ≤ 94% while breathing ambient air.
- •Calculation through validated Sat/FiO2 scales is allowed. P/F value of reference if the last available before the signature of consent.
- •Need of supplemental oxygen (i.e. new use of supplemental oxygen, or increased oxygen requirement if on chronic oxygen) requiring low- or high-flow oxygen or non-invasive mechanical ventilation (7-point WHO-OS category 4 or 5).
- •Radiological chest imaging (X-rays, CT scan) confirms lung involvement and inflammation.
Exclusion Criteria
- •Cannot obtain informed consent.
- •Hepatic dysfunction with Child Pugh score B or C, or ALT or AST\> 5 times the upper limit.
- •Renal dysfunction with estimated glomerular filtration rate (MDRD) \< 50 mL/min/1.73 m2 or patient receiving continuous renal replacement therapy, hemodialysis, or peritoneal dialysis.
- •Bacterial sepsis (besides COVID-19 sepsis).
- •Known congenital or acquired immune deficiency.
- •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.
Arms & Interventions
Reparixin
Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care
Intervention: Reparixin
Placebo
placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care.
Intervention: Placebo
Outcomes
Primary Outcomes
Proportion of Patients Alive and Free of Respiratory Failure at Day 28
Time Frame: At day 28
The event variable is defined as "the proportion of patients alive and free of respiratory failure at Day 28". This means no need of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) or admission to intensive care unit (ICU) linked to worsening of respiratory parameters compared to baseline.
Secondary Outcomes
- Incidence of ICU Admission Until Day 28(Until day 28)
- Percentage of Participants With Clinical Improvement 2 up to Day 28(At Day 28)
- Proportion of Patients Alive and Free of Respiratory Failure at Fixed Timepoints(At Days 3, 7(±1),14(±2), 21(±2) and 90(±2) after randomization (randomization = day 1))
- Number of Patients With Clinical Improvement 1 up to Day 28 (Decline of 1 Category in the 7-point WHO-OS)(Day 1 (baseline), Days 3, 7, 14, 21, 28.)
- Mortality Rates up to Day 28(Up to Day 28)
- Proportion of Patients Alive and Free of Respiratory Failure at Day 60(At day 60)
- Duration of Supplemental Oxygen Treatment up to Day 28(From baseline up to day 28)
- Number of Patients Requiring Invasive Mechanical Ventilation Use, or ECMO up to Day 28 and up to Day 60(day 28 and Day 60)
- Duration of ICU Admission up to Day 60(Up to day 60)
- Time to Recovery (Category 1 - 2 - 3 of the 7-point WHO Ordinal Scale of Clinical Improvement (WHO-OS)) Until Day 28(Until Day 28)
- Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints(At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months))
- Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points(At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months))
- Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2).(At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months))
- Duration of Non-invasive Mechanical Ventilation up to Day 60(From baseline up to day 60)
- Mortality Rates up to Days 60 and 90(up to Days 60 and 90)
- Percentage of Participants With Clinical Improvement 1 up to Day 28(At day 28)
- Change From Baseline in Dyspnea Severity (VAS Scale) at Fixed Timepoints(At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months))
- Duration of Invasive Mechanical Ventilation, or ECMO up to Day 60(Up to day 60)
- Number of Subjects Who Exhibited at Least 1 TEAE, at Least 1 Severe TEAE, at Least 1 Serious TEAE, at Least 1 Non-serious TEAE, at Least 1 ADR, at Least 1 Serious ADR, at Least 1 TEAE Leading to Discontinuation of IMP, Etc.(Throughout the study, till Day 90 (= end of the follow-up period).)
- Number of Patients With Clinical Improvement 2 up to Day 28 (Decline of 2 Categories in the 7-point WHO-OS)(Day 1 (baseline), Days 3, 7, 14, 21, 28)
- Time to Discharge From Hospital up to Day 28(Day 1 (baseline), Days 3, 7, 14, 21, 28)
- Freedom From (Time to) Death or Respiratory Failure up to Day 90(at baseline, day 3, day 7, day 14, day 21, day 28, day 60, day 90)
- The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints(At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months))
- Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2)(At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months))
- Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio.(At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months))
- Change From Baseline to Fixed Endpoints in High-Sensitivity C Reactive Protein (Hs-CRP)(At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months))