Evaluation of the Pharmacokinetics and Pharmacodynamics of Hydroxychloroquine in COVID-19 Intensive Care Unit Patients (PREAVIS)
Primary Purpose
Sars-CoV2
Status
Terminated
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Hydroxychloroquine (HCQ)
Sponsored by
About this trial
This is an interventional treatment trial for Sars-CoV2 focused on measuring SARS-CoV-2, Hydroxychloroquine, COVID-19, Intensive care unit, Pharmacokinetics
Eligibility Criteria
Inclusion Criteria:
- Adult patients 18 years of age and older
- Patients hospitalized in the intensive care unit infected with CoV-2-SARS for whom a diagnosis of respiratory CoV-2-SARS infection has been made by nasopharyngeal swab or deep respiratory sampling.
- Patient receiving HCQ treatment as part of care or as part of a clinical trial.
- Patient affiliated or entitled to a social security scheme
Exclusion Criteria:
- Hypersensitivity to the active substances or to any of the following excipients: lactose monohydrate, povidone, corn starch, magnesium stearate.
- Retinopathies
- Combination with citalopram, escitalopram, hydroxyzine, domperidone and piperazine due to increased risk of ventricular rhythm disturbances, including torsades de pointes.
- Patient with known QT prolongation
- Known deficit in G6PD
- Pregnant woman
Sites / Locations
- Groupement Hospitalier des Portes de Province
- Centre Hospitalier de Roanne
- CHU Saint-Etienne
- Clinique Mutualiste
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Patients infected by SARS-CoV-2 treated by Hydroxychloroquine
Arm Description
Blood sample on patients infected by SARS-CoV-2 treated by Hydroxychloroquine
Outcomes
Primary Outcome Measures
Pharmacokinetics of hydroxychloroquine (HCQ)
measured blood concentration by blood sample results.
Secondary Outcome Measures
Correlation between hydroxychloroquine (HCQ) concentration and cardiac toxicity (QT interval)
measured by blood sample and electrocardiogram results.
Correlation between Pharmacokinetic (concentration) and pharmacodynamic (viral load) of hydroxychloroquine (HCQ)
measured by blood sample
Pharmacokinetic model
Pharmacokinetic (area under the curve) analysis will be performed using a population approach with a non-linear mixed effects model.
Full Information
NCT ID
NCT04522466
First Posted
August 19, 2020
Last Updated
September 4, 2020
Sponsor
Centre Hospitalier Universitaire de Saint Etienne
Collaborators
CHU Saint-Etienne - Laboratoire de Pharmacologie - Toxicologie - Gaz du sang
1. Study Identification
Unique Protocol Identification Number
NCT04522466
Brief Title
Evaluation of the Pharmacokinetics and Pharmacodynamics of Hydroxychloroquine in COVID-19 Intensive Care Unit Patients
Acronym
PREAVIS
Official Title
Evaluation of the Pharmacokinetics and Pharmacodynamics of Hydroxychloroquine in COVID-19 Intensive Care Unit Patients
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Terminated
Why Stopped
Stop of the study by competent authority (ANSM)
Study Start Date
April 3, 2020 (Actual)
Primary Completion Date
May 28, 2020 (Actual)
Study Completion Date
May 28, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Saint Etienne
Collaborators
CHU Saint-Etienne - Laboratoire de Pharmacologie - Toxicologie - Gaz du sang
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
To date, no treatment has demonstrated clinical efficacy on COVID 19. However, several therapeutic strategies are being considered and are being evaluated in numerous clinical trials. Among these strategies, the use of hydroxychloroquine (HCQ) seems promising. There is very little information on how to precisely administer hydroxychloroquine to patients infected with SARS-CoV-2 in intensive care, which may be responsible for side effects, some of which are potentially serious. In addition, this treatment has a long half-life which increases the risk of accumulation and therefore toxicity. In view of the lack of knowledge on the pharmacokinetic / pharmacodynamic properties of hydroxychloroquine in intensive care patients infected with SARS-CoV-2, we propose to perform a prospective multicenter cohort study in order to collect the biological data necessary for this evaluation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sars-CoV2
Keywords
SARS-CoV-2, Hydroxychloroquine, COVID-19, Intensive care unit, Pharmacokinetics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Patients infected by SARS-CoV-2 treated by Hydroxychloroquine
Arm Type
Experimental
Arm Description
Blood sample on patients infected by SARS-CoV-2 treated by Hydroxychloroquine
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine (HCQ)
Intervention Description
Hydroxychloroquine (HCQ) will be administered as usual practice: dosage is adjusted to maintain a concentration between 1 and 2 mg/L.
Measure pharmacokinetics and pharmacodynamics of Hydroxychloroquine (HCQ).
Primary Outcome Measure Information:
Title
Pharmacokinetics of hydroxychloroquine (HCQ)
Description
measured blood concentration by blood sample results.
Time Frame
Up to day 21
Secondary Outcome Measure Information:
Title
Correlation between hydroxychloroquine (HCQ) concentration and cardiac toxicity (QT interval)
Description
measured by blood sample and electrocardiogram results.
Time Frame
Up to day 21
Title
Correlation between Pharmacokinetic (concentration) and pharmacodynamic (viral load) of hydroxychloroquine (HCQ)
Description
measured by blood sample
Time Frame
Day 1, Day 3, Day 5, Day 7, Day 14, Day 21
Title
Pharmacokinetic model
Description
Pharmacokinetic (area under the curve) analysis will be performed using a population approach with a non-linear mixed effects model.
Time Frame
Up to day 21
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult patients 18 years of age and older
Patients hospitalized in the intensive care unit infected with CoV-2-SARS for whom a diagnosis of respiratory CoV-2-SARS infection has been made by nasopharyngeal swab or deep respiratory sampling.
Patient receiving HCQ treatment as part of care or as part of a clinical trial.
Patient affiliated or entitled to a social security scheme
Exclusion Criteria:
Hypersensitivity to the active substances or to any of the following excipients: lactose monohydrate, povidone, corn starch, magnesium stearate.
Retinopathies
Combination with citalopram, escitalopram, hydroxyzine, domperidone and piperazine due to increased risk of ventricular rhythm disturbances, including torsades de pointes.
Patient with known QT prolongation
Known deficit in G6PD
Pregnant woman
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sophie PERINEL, MD
Organizational Affiliation
CHU Saint-Etienne
Official's Role
Principal Investigator
Facility Information:
Facility Name
Groupement Hospitalier des Portes de Province
City
Montélimar
Country
France
Facility Name
Centre Hospitalier de Roanne
City
Roanne
Country
France
Facility Name
CHU Saint-Etienne
City
Saint-Étienne
Country
France
Facility Name
Clinique Mutualiste
City
Saint-Étienne
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Evaluation of the Pharmacokinetics and Pharmacodynamics of Hydroxychloroquine in COVID-19 Intensive Care Unit Patients
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