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Reparixin in COVID-19 Pneumonia - Efficacy and Safety

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04794803
Recruitment Status : Terminated (The sponsor has decided to start with a separate protocol for phase 3 and therefore this study was terminated with only phase 2.)
First Posted : March 12, 2021
Results First Posted : March 17, 2022
Last Update Posted : May 24, 2022
Sponsor:
Information provided by (Responsible Party):
Dompé Farmaceutici S.p.A

Tracking Information
First Submitted Date  ICMJE March 8, 2021
First Posted Date  ICMJE March 12, 2021
Results First Submitted Date  ICMJE February 21, 2022
Results First Posted Date  ICMJE March 17, 2022
Last Update Posted Date May 24, 2022
Actual Study Start Date  ICMJE May 5, 2020
Actual Primary Completion Date November 27, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 15, 2022)
Phase 2 - Percentage of Participants With Composite Endpoint of Clinical Events [ Time Frame: Up to Day 1 ]
Composite event is defined as the onset of at least one of the following events:
  • supplemental oxygen requirement based on a worsening of PaO2/FiO2 ratio,
  • invasive mechanical ventilation use,
  • admission to Intensive Care Unit (ICU),
  • use of a rescue medication for any reason. Please note that in the measure type "number" actually is a "rate" of patients. Rate is referred to a binomial response rate while the 95% CIs are estimated by using the Clopper-Pearson's method
Original Primary Outcome Measures  ICMJE
 (submitted: March 11, 2021)
  • Phase 2 primary endpoint - Composite endpoint of clinical events [ Time Frame: Baseline ]
    The patient requires at least one of the following: supplemental oxygen requirement, mechanical ventilation use, admission to Intensive Care Unit (ICU), and use of a rescue medication for any reason
  • Phase 2 primary endpoint - Composite endpoint of clinical events [ Time Frame: day 1 ]
    The patient requires at least one of the following: supplemental oxygen requirement, mechanical ventilation use, admission to Intensive Care Unit (ICU), and use of a rescue medication for any reason
  • Phase 2 primary endpoint - Composite endpoint of clinical events [ Time Frame: day 2 ]
    The patient requires at least one of the following: supplemental oxygen requirement, mechanical ventilation use, admission to Intensive Care Unit (ICU), and use of a rescue medication for any reason
  • Phase 2 primary endpoint - Composite endpoint of clinical events [ Time Frame: week 1 ]
    The patient requires at least one of the following: supplemental oxygen requirement, mechanical ventilation use, admission to Intensive Care Unit (ICU), and use of a rescue medication for any reason
  • Phase 2 primary endpoint - Composite endpoint of clinical events [ Time Frame: day 21(end of treatment) ]
    The patient requires at least one of the following: supplemental oxygen requirement, mechanical ventilation use, admission to Intensive Care Unit (ICU), and use of a rescue medication for any reason
  • Phase 2 primary endpoint - Composite endpoint of clinical events [ Time Frame: Follow-up (FU) (7±3 days after treatment period) ]
    The patient requires at least one of the following: supplemental oxygen requirement, mechanical ventilation use, admission to Intensive Care Unit (ICU), and use of a rescue medication for any reason
  • Phase 3 Primary Endpoint: Composite endpoint of death and of severe clinical events [ Time Frame: Baseline ]
    The patient dies or requires mechanical ventilation use and/or admission to ICU
  • Phase 3 Primary Endpoint: Composite endpoint of death and of severe clinical events [ Time Frame: day 1 ]
    The patient dies or requires mechanical ventilation use and/or admission to ICU
  • Phase 3 Primary Endpoint: Composite endpoint of death and of severe clinical events [ Time Frame: day 2 ]
    The patient dies or requires mechanical ventilation use and/or admission to ICU
  • Phase 3 Primary Endpoint: Composite endpoint of death and of severe clinical events [ Time Frame: week 1 ]
    The patient dies or requires mechanical ventilation use and/or admission to ICU
  • Phase 3 Primary Endpoint: Composite endpoint of death and of severe clinical events [ Time Frame: day 21(end of treatment) ]
    The patient dies or requires mechanical ventilation use and/or admission to ICU
  • Phase 3 Primary Endpoint: Composite endpoint of death and of severe clinical events [ Time Frame: Follow-up (FU) (7±3 days after treatment period) ]
    The patient dies or requires mechanical ventilation use and/or admission to ICU
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 15, 2022)
  • Phase 2 - Percentage of Patients With Improvement in Clinical Severity Score (as Recommended by WHO for COVID Studies) of at Least Two Points [ Time Frame: At day 1, day 2, week 1, day 21(end of treatment, EOT), EOS (end of study, i.e. 7±3 days after EOT) ]
    Changes in clinical severity score are defined as the time to clinical improvement of two points from the time of randomization on a seven-category ordinal scale or live discharge from the hospital, whichever came first. The seven-category ordinal scale consisted of the following: 1) not hospitalized, with resumption of normal activities; 2) not hospitalized, but unable to resume normal activities; 3) hospitalized, not requiring supplemental oxygen; 4) hospitalized, requiring supplemental oxygen; 5) hospitalized, requiring high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 6) hospitalized, requiring Extracorporeal Membrane Oxygenation (ECMO), invasive mechanical ventilation, or both; and 7) death. The higher the score, the worse the outcome. A subject is considered "improved" with a clinical severity score improvement of at least two points compared to randomization or live discharge from the hospital. n are the subjects improved at each time point vs baseline.
  • Phase 2 - Percentage of Improved Subjects in Dyspnea Severity, Assessed by Liker Scale [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment, EOT), 7±3 days after treatment period (end of study, EOS) ]
    The severity of dyspnea can be measured through the Liker scale. The Liker scale is used as follows: the patient grades his current breathing compared to when he first started the drug (from -3 to 3). "0" = no change, "1" =minimally better, "2" =moderately better, "3" =markedly better, "-1" =minimally worse, "-2" =moderately worse, "-3" =markedly worse. The higher the score, the better the outcome. N is the number of subjects for which the evaluation of the dyspnea severity scale at each time point is available. n is the number of subjects improved at each time point in comparison with the randomization.
  • Phase 2 - Change From Baseline in Dyspnea Severity, Assessed by VAS Scale [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment, EOT), 7±3 days after treatment period (end of study, EOS) ]
    The severity of dyspnea is measured also through the VAS scale. The VAS scale is used as follows: the patient draws a horizontal line on an axial graph (from 0 to 100) to show the degree of how he feels about breathing. The number "0" equals the worst breathing the patient has ever felt and the number "100" equals the best he has ever felt. N is the number of subjects for which the evaluation of the dyspnea severity scale at each time point is available. n is the number of subjects improved at each time point in comparison with the randomization.
  • Changes From Baseline in Body Temperature to Any Post-baseline Timepoints [ Time Frame: Baseline, Day 1, Day 2, Week 1, EOT and EOS ]
    Variations in the mean body temperature from baseline to any post-baseline timepoint were assessed. n is the number of subjects for which the evaluation of the body temperature at each time point is available.
  • Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to PaO2/FiO2 [ Time Frame: At day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    Cumulative quantity of oxygen treatment (L) = Sum of all Quantity (L) in CONCOMITANT OXYGEN TREATMENT form, from randomization to time point of interest. According to PaO2/FiO2, the classification is 'mild' if 200 <= PaO2/FiO2 < 300 mmHg, 'moderate' if 100 <= PaO2/FiO2 < 200 mmHg, 'severe' if PaO2/FiO2 < 100 mmHg. A patient with ARDS (PaO2/FiO2<300 mmHg) is considered 'worsened' in case of a decrease of PaO2/FiO2 of at least one third (-33,3%) from the baseline PaO2/FiO2 value. NOTE that: N is the number of subjects for which the evaluation of the PaO2/FiO2 ratio at each time point is available. While n is the number of subjects worsened at each time point in comparison with the randomization, expressed in percentage.
  • Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to Oxygen Delivery System Classification [ Time Frame: day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    Duration of oxygen administration (hours) = Administration end date/time - Administration start date/time / 60. N is the number of subjects for which the evaluation of the Oxygen Delivery System Classification at each time point is available. n is the number of subjects worsened at each time point, expressed in percentage, in comparison with the randomization. According to Oxygen Delivery System, the classification is 'invasive' if there is Invasive Medicinal Ventilation or ECMO, else 'high flow' if there is High Flow Nasal Cannula or BIPAP or CPAP, else 'low flow' if there is Nasal Cannula or Mask then Class=Low Flow Classification. A patient is considered 'Worsened' after baseline if there is an increase in the level of severity within the oxygen delivery system classification (Invasive > High Flow > Low Flow).
  • Phase 2 - Oxygen Cumulative Duration During the Study [ Time Frame: Week 1, EOT, EOS ]
    This outcome assesses the oxygen cumulative duration during the study. N is the number of subjects for which the evaluation of the PaO2/FiO2 ratio or Oxygen Delivery System Classification at each time point is available. n is the number of subjects worsened at each time point in comparison with the randomization.
  • Phase 2 - Oxygen Cumulative Quantity During the Study [ Time Frame: Week 1, EOT and EOS ]
    In this endpoint is assessed the oxygen cumulative quantity needed at each single timepoint. N is the number of subjects for which the evaluation of the PaO2/FiO2 ratio or Oxygen Delivery System Classification at each time point is available. n is the number of subjects worsened at each time point in comparison with the randomization.
  • Phase 2 - Percentage of Subjects Requiring Mechanical Ventilation Use, Overall [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    Percentage along with the 95% confidence interval (Clopper-Pearson's formula) of subjects requiring mechanical ventilation are calculated and compared. N is the number of subjects for which the evaluation of the use of mechanical ventilation is available. n is the number, expressed in percentage, of subjects requiring mechanical ventilation, overall.
  • Phase 2 - Cumulative Duration of Mechanical Ventilation Use, Overall [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    Cumulative duration of mechanical ventilation (in hours) = Sum of duration of mechanical ventilation (hours) in mechanical ventilation form, from randomization to time point of interest. Duration of mechanical ventilation (hours) = End date/time - Start date/time / 60. n is the number of subjects for which the evaluation of the use of mechanical ventilation is available
  • Phase 2 - Percentage of Subjects With Intensive Care Unit (ICU) Admission Need [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    Percentage, along with the 95% confidence interval (Clopper-Pearson's formula), of subjects requiring ICU admission are calculated and compared.N is the number of subjects for which the evaluation of the ICU admission need is available.
  • Phase 2 - Cumulative ICU Stay [ Time Frame: Day 1, Day 2, Week 1, EOT, EOS ]
    Cumulative ICU stay was assessed at different timepoints and measured in days
  • Phase 2 - Lung Damage Extension by Severity and by Timepoint [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    Lung damage extensions is assessed by Chest CT or Rx. This damage can be as follows: "none", "trace", "mild", "moderate", or "severe". N is the number of subjects for which the evaluation of the lung damage extension at each time point is available.
  • Phase 2 - Lung Exudation by Severity and by Timepoint [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    Lung exudation is assessed by Chest CT or Rx. This can be as follows: "none", "trace", "mild", "moderate", or "severe". N is the number of subjects for which the evaluation of the lung damage extension at each time point is available.
  • Phase 2 - Change From Baseline in Partial Arterial Oxygen Pressure (PaO2) [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    PaO2 measures the pressure of oxygen dissolved in the blood and how well oxygen is able to move from the airspace of the lungs into the blood. Normally, PaO2 is between 75 and 100 mmHg (at sea level). Lower levels indicate an unsufficient amount of oxygen flowing from the alveoli to the blood. Please note that a significant proportion of patients in both groups did not have post-baseline assessments of PaO2.
  • Phase 2 - Change From Baseline in Oxygen Saturation (SpO2) [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    SpO2 measures the amount of oxygen-carrying hemoglobin in the blood relative to the amount of hemoglobin not carrying oxygen. Acceptable normal ranges for patients without pulmonary pathology are from 95 to 99 percent.
  • Phase 2 - Partial Arterial Oxygen Pressure (PaO2) to Fraction of Inspiration O2 (FiO2) Ratio [PaO2/FiO2 Ratio] [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    PaO2/FiO2 ratio is the ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2 expressed as a fraction, not a percentage) also known as the Horowitz index, the Carrico index, and (most conveniently) the P/F ratio at sea level, the normal PaO2/FiO2 ratio is ~ 400-500 mmHg (~55-65 kPa).
  • Phase 2 - Change From Baseline in Reactive Protein (CRP) [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    For a standard CRP test, a normal reading is less than 10 milligram per liter (mg/L). Levels between 10 mg/L and 100 mg/L are moderately elevated and are usually due to more significant inflammation from an infectious or non-infectious cause. Inflammatory status is documented by C-reactive protein (CRP) ≥ 100mg/L.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2021)
  • Phase 2/3 Secondary Endpoint: Changes in clinical severity score (as recommended by the World Health Organization -WHO- for COVID studies) [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (7±3 days after treatment period) ]
    The time to clinical improvement of two points from the time of randomization on a seven-category ordinal scale or live discharge from the hospital, whichever comes first. The seven-category ordinal scale consists of the following: 1) not hospitalized, with resumption of normal activities; 2) not hospitalized, but unable to resume normal activities; 3) hospitalized, not requiring supplemental oxygen; 4) hospitalized, requiring supplemental oxygen; 5) hospitalized, requiring high-flow oxygen therapy, noninvasive mechanical ventilation, or both; 6) hospitalized, requiring ECMO, invasive mechanical ventilation, or both; and 7) death.
  • Phase 2/3 Secondary Endpoint: Dyspnea severity [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    The severity of dyspnea is measured through the Liker scale and the VAS scale. The Liker scale is used as follows: the patient grades his current breathing compared to when he first started the drug (from -3 to 3). "0" = no change, "1" =minimally better, "2" =moderately better, "3" =markedly better, "-1" =minimally worse, "-2" =moderately worse, "-3" =markedly worse. The VAS scale is used as follows: the patient draws a horizontal line on an axial graph (from 0 to 100) to show the degree of how he feels about breathing. The number "0" equals the worst breathing the patient has ever felt and the number "100" equals the best he has ever felt.
  • Phase 2/3 Secondary Endpoint: duration of supplemental oxygen treatment [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    Duration of oxygen administration (hours) = Administration end date/time - Administration start date/time / 60.
  • Phase 2/3 Secondary Endpoint: quantity of supplemental oxygen treatment [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    Cumulative quantity of oxygen treatment (L) = Sum of all Quantity (L) in CONCOMITANT OXYGEN TREATMENT form, from randomization to time point of interest.
  • Phase 2/3 Secondary Endpoint: Incidence of mechanical ventilation use [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    Proportion along with the 95% confidence interval (Clopper-Pearson's formula) of subjects requiring mechanical ventilation are calculated and compared.
  • Phase 2/3 Secondary Endpoint: duration of mechanical ventilation use [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    Cumulative duration of mechanical ventilation (hours) = Sum of duration of mechanical ventilation (hours) in mechanical ventilation form, from randomization to time point of interest. Duration of mechanical ventilation (hours) = End date/time - Start date/time / 60
  • Phase 2/3 Secondary Endpoint: Incidence of intensive care unit (ICU) admission need [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    Proportion along with the 95% confidence interval (Clopper-Pearson's formula) of subjects requiring ICU admission are calculated and compared.
  • Phase 2/3 Secondary Endpoint: Lung damage extension changes from baseline [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    Lung damage extentions is assessed by Chest CT or Rx
  • Phase 2/3 Secondary Endpoint: Change from baseline in lung exudation degree [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    Lung exudation degree is assessed by Chest CT or Rx
  • Phase 2/3 Secondary Endpoint: PaO2 [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    PaO2 measures the pressure of oxygen dissolved in the blood and how well oxygen is able to move from the airspace of the lungs into the blood. Normally, PaO2 is between 75 and 100 mmHg (at sea level). Lower levels indicate an unsufficient amount of oxygen flowing from the alveoli to the blood.
  • Phase 2/3 Secondary Endpoint: SpO2 [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    SpO2 measures the amount of oxygen-carrying hemoglobin in the blood relative to the amount of hemoglobin not carrying oxygen. Acceptable normal ranges for patients without pulmonary pathology are from 95 to 99 percent.
  • Phase 2/3 Secondary Endpoint: Partial arterioral oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    PaO2/FiO2 ratio is the ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2 expressed as a fraction, not a percentage) also known as the Horowitz index, the Carrico index, and (most conveniently) the P/F ratio at sea level, the normal PaO2/FiO2 ratio is ~ 400-500 mmHg (~55-65 kPa).
  • Phase 2/3 Secondary Endpoint: C-reactive protein (CRP) [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    For a standard CRP test, a normal reading is less than 10 milligram per liter (mg/L). Levels between 10 mg/L and 100 mg/L are moderately elevated and are usually due to more significant inflammation from an infectious or non-infectious cause. Inflammatory status is documented by C-reactive protein (CRP) ≥ 100mg/L.
  • Phase 2/3 Secondary Endpoint: Hs-CRP [ Time Frame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period) ]
    The hs-CRP test detects lower levels of CRP in the bloodstream (0.5-10 mg/L), whereas the CRP test measures levels in a higher range (10-1,000 mg/L).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Reparixin in COVID-19 Pneumonia - Efficacy and Safety
Official Title  ICMJE Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients With COVID-19 Pneumonia
Brief Summary
  • Phase 2 Study Objectives: efficacy and safety of of Reparixin treatment as compared to the control arm in adult patients with severe COVID-19 pneumonia
  • Phase 3 Study Objectives: efficacy and safety of Reparixin treatment as compared to the control arm in adult patients with moderate or severe COVID-19 pneumonia
Detailed Description

This clinical trial is an adaptive phase 2/3, randomized, controlled multicenter study on the efficacy and safety of Reparixin in the treatment of hospitalized patients with COVID-19 pneumonia. 48 patients are planned to be enrolled in Phase 2 and an estimated total of 111 patients are planned to be enrolled up to the end of Phase 3, with a randomization 2:1 Reparixin vs Control (Standard of care).

In the phase 2 segment of this study, patients are randomized 2:1 to Reparixin oral tablets 1200 mg (Group 1, active treatment) or standard of care (Group 2, control arm). In case of worsening (e.g. need of ICU and/or mechanical ventilation) after the first 24hrs, patients are offered a rescue medication with no restriction from the sponsor and fully based on their physicians' judgement.

In the phase 3 segment of this study, it is planned that patients are randomized 2:1 to Reparixin or standard of care. The Phase 3 design will be reassessed and decided based on the results of the Phase 2.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Severe Pneumonia
Intervention  ICMJE
  • Drug: Reparixin
    Reparixin was administered via oral tablets 1200 mg TID for 7 days. In case of improvement, treatment can be prolonged at discretion of the investigator up to a maximum of 21 days of treatment in total or live discharge from the hospital, whichever comes first.
    Other Name: Repertaxin L-lysine salt
  • Drug: Standard of care
    Standard of care
    Other Name: Control
Study Arms  ICMJE
  • Experimental: Reparixin
    Reparixin oral tablets 1200 mg TID for 7 days
    Intervention: Drug: Reparixin
  • Active Comparator: Standard of care
    Standard of care
    Intervention: Drug: Standard of care
Publications * Landoni G, Piemonti L, Monforte AD, Grossi P, Zangrillo A, Bucci E, Allegretti M, Goisis G, Gavioli EM, Patel N, De Pizzol M, Pasedis G, Mantelli F. A Multicenter Phase 2 Randomized Controlled Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients with COVID-19 Pneumonia. Infect Dis Ther. 2022 Aug;11(4):1559-1574. doi: 10.1007/s40121-022-00644-6. Epub 2022 May 26.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 15, 2022)
56
Original Actual Enrollment  ICMJE
 (submitted: March 11, 2021)
55
Actual Study Completion Date  ICMJE February 2, 2021
Actual Primary Completion Date November 27, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Phase 2 Inclusion Criteria:

    1. Age 18 to 90.
    2. Confirmed COVID-19 diagnosis
    3. At least one of the following: # Respiratory distress, RR ≥ 30 breaths/min without oxygen; # Partial arterial oxygen pressure (PaO2) / Fraction of inspiration O2 (FiO2) >100 <300mmHg

    (1mmHg = 0.133kPa). 4. Chest imaging confirms lung involvement and inflammation. 5. Inflammatory status as documented by at least one of the following: Lactate dehydrogenase (LDH) > normal range, C-reactive protein (CRP) ≥ 100mg/L or IL-6 ≥ 40pg/mL, serum ferritin ≥ 900ng/mL, XDP >20mcg/mL.

  • Phase 3 Inclusion Criteria: Same as above; other criteria TBD based on Phase 2 outcomes.

Exclusion Criteria:

• Phase 2/3 Exclusion Criteria:

  1. Cannot obtain informed consent.
  2. Severe hepatic dysfunction (Child Pugh score ≥ C, or AST> 5 times the upper limit); Severe renal dysfunction (estimated glomerular filtration rate ≤ 30mL / min / 1.73 m2) or receive continuous renal replacement therapy, hemodialysis, or peritoneal dialysis.
  3. Patients with hypersensitivity to ibuprofen or to more than one non steroidal anti-inflammatory drug or to more than one medication belonging to the class of sulfonamides (e.g. sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib; hypersensitivity to sulphanilamide antibiotics alone, e.g. sulfamethoxazole, does not qualify for exclusion)
  4. Severe, active bleeding such as hemoptysis, gastrointestinal bleeding, central nervous system bleeding, and nosebleeds within 1 month before enrollment.
  5. Pregnant and lactating women and those planning to get pregnant.
  6. Participated in other interventional clinical trials with investigational medicinal products, not considered suitable for this study by the researchers.
  7. At the time of enrollment, patients not in a clinical condition compatible with the oral administration of the study drug.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04794803
Other Study ID Numbers  ICMJE REPAVID-19
2020-001645-40 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Dompé Farmaceutici S.p.A
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Dompé Farmaceutici S.p.A
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lorenzo Piemonti, MD PhD Ospedale San Raffaele
Principal Investigator: Alberto Zangrillo, MD PhD Ospedale San Raffaele
PRS Account Dompé Farmaceutici S.p.A
Verification Date May 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP