Back to resultsReparixin in COVID-19 Pneumonia - Efficacy and Safety
Primary Purpose
Severe Pneumonia
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Reparixin
Standard of care
Sponsored by
About this trial
This is an interventional treatment trial for Severe Pneumonia focused on measuring COVID-19
Eligibility Criteria
Inclusion Criteria:
Phase 2 Inclusion Criteria:
- Age 18 to 90.
- Confirmed COVID-19 diagnosis
- 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:
- Cannot obtain informed consent.
- 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.
- 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)
- Severe, active bleeding such as hemoptysis, gastrointestinal bleeding, central nervous system bleeding, and nosebleeds within 1 month before enrollment.
- Pregnant and lactating women and those planning to get pregnant.
- Participated in other interventional clinical trials with investigational medicinal products, not considered suitable for this study by the researchers.
- At the time of enrollment, patients not in a clinical condition compatible with the oral administration of the study drug.
Sites / Locations
- Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina de São Paulo
- Ospedale San Paolo
- Ospedale San Raffaele
- Ospedale di Varese
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Reparixin
Standard of care
Arm Description
Reparixin oral tablets 1200 mg TID for 7 days
Standard of care
Outcomes
Primary Outcome Measures
Phase 2 - Percentage of Participants With Composite Endpoint of Clinical Events
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
Secondary Outcome Measures
Phase 2 - Percentage of Patients With Improvement in Clinical Severity Score (as Recommended by WHO for COVID Studies) of at Least Two Points
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
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
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
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
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
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
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
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
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
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
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
Cumulative ICU stay was assessed at different timepoints and measured in days
Phase 2 - Lung Damage Extension by Severity and by Timepoint
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
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)
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)
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]
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)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04794803
Brief Title
Reparixin in COVID-19 Pneumonia - Efficacy and Safety
Official Title
Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients With COVID-19 Pneumonia
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Terminated
Why Stopped
The sponsor has decided to start with a separate protocol for phase 3 and therefore this study was terminated with only phase 2.
Study Start Date
May 5, 2020 (Actual)
Primary Completion Date
November 27, 2020 (Actual)
Study Completion Date
February 2, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dompé Farmaceutici S.p.A
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Pneumonia
Keywords
COVID-19
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
56 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Reparixin
Arm Type
Experimental
Arm Description
Reparixin oral tablets 1200 mg TID for 7 days
Arm Title
Standard of care
Arm Type
Active Comparator
Arm Description
Standard of care
Intervention Type
Drug
Intervention Name(s)
Reparixin
Other Intervention Name(s)
Repertaxin L-lysine salt
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Standard of care
Other Intervention Name(s)
Control
Intervention Description
Standard of care
Primary Outcome Measure Information:
Title
Phase 2 - Percentage of Participants With Composite Endpoint of Clinical Events
Description
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
Time Frame
Up to Day 1
Secondary Outcome Measure Information:
Title
Phase 2 - Percentage of Patients With Improvement in Clinical Severity Score (as Recommended by WHO for COVID Studies) of at Least Two Points
Description
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.
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)
Title
Phase 2 - Percentage of Improved Subjects in Dyspnea Severity, Assessed by Liker Scale
Description
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.
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)
Title
Phase 2 - Change From Baseline in Dyspnea Severity, Assessed by VAS Scale
Description
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.
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)
Title
Changes From Baseline in Body Temperature to Any Post-baseline Timepoints
Description
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.
Time Frame
Baseline, Day 1, Day 2, Week 1, EOT and EOS
Title
Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to PaO2/FiO2
Description
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.
Time Frame
At day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Title
Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to Oxygen Delivery System Classification
Description
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).
Time Frame
day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Title
Phase 2 - Oxygen Cumulative Duration During the Study
Description
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.
Time Frame
Week 1, EOT, EOS
Title
Phase 2 - Oxygen Cumulative Quantity During the Study
Description
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.
Time Frame
Week 1, EOT and EOS
Title
Phase 2 - Percentage of Subjects Requiring Mechanical Ventilation Use, Overall
Description
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.
Time Frame
Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Title
Phase 2 - Cumulative Duration of Mechanical Ventilation Use, Overall
Description
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
Time Frame
Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Title
Phase 2 - Percentage of Subjects With Intensive Care Unit (ICU) Admission Need
Description
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.
Time Frame
Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Title
Phase 2 - Cumulative ICU Stay
Description
Cumulative ICU stay was assessed at different timepoints and measured in days
Time Frame
Day 1, Day 2, Week 1, EOT, EOS
Title
Phase 2 - Lung Damage Extension by Severity and by Timepoint
Description
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.
Time Frame
Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Title
Phase 2 - Lung Exudation by Severity and by Timepoint
Description
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.
Time Frame
Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Title
Phase 2 - Change From Baseline in Partial Arterial Oxygen Pressure (PaO2)
Description
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.
Time Frame
Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Title
Phase 2 - Change From Baseline in Oxygen Saturation (SpO2)
Description
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.
Time Frame
Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Title
Phase 2 - Partial Arterial Oxygen Pressure (PaO2) to Fraction of Inspiration O2 (FiO2) Ratio [PaO2/FiO2 Ratio]
Description
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).
Time Frame
Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Title
Phase 2 - Change From Baseline in Reactive Protein (CRP)
Description
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.
Time Frame
Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Phase 2 Inclusion Criteria:
Age 18 to 90.
Confirmed COVID-19 diagnosis
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:
Cannot obtain informed consent.
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.
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)
Severe, active bleeding such as hemoptysis, gastrointestinal bleeding, central nervous system bleeding, and nosebleeds within 1 month before enrollment.
Pregnant and lactating women and those planning to get pregnant.
Participated in other interventional clinical trials with investigational medicinal products, not considered suitable for this study by the researchers.
At the time of enrollment, patients not in a clinical condition compatible with the oral administration of the study drug.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lorenzo Piemonti, MD PhD
Organizational Affiliation
Ospedale San Raffaele
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alberto Zangrillo, MD PhD
Organizational Affiliation
Ospedale San Raffaele
Official's Role
Principal Investigator
Facility Information:
Facility Name
Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina de São Paulo
City
São Paulo
ZIP/Postal Code
05403-900
Country
Brazil
Facility Name
Ospedale San Paolo
City
Milan
State/Province
Lombardy
ZIP/Postal Code
20100
Country
Italy
Facility Name
Ospedale San Raffaele
City
Milan
State/Province
Lombardy
ZIP/Postal Code
20100
Country
Italy
Facility Name
Ospedale di Varese
City
Varese
State/Province
Lombardy
Country
Italy
12. IPD Sharing Statement
Citations:
PubMed Identifier
35618953
Citation
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.
Results Reference
derived
Learn more about this trial
Reparixin in COVID-19 Pneumonia - Efficacy and Safety
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