Evaluation of the Pharmacokinetics and Pharmacodynamics of Hydroxychloroquine in COVID-19 Intensive Care Unit Patients

Study Overview
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Brief Summary
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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.

Official Title
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Evaluation of the Pharmacokinetics and Pharmacodynamics of Hydroxychloroquine in COVID-19 Intensive Care Unit Patients

Conditions
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Sars-CoV2

Intervention / Treatment
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* Drug: Hydroxychloroquine (HCQ)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients infected by SARS-CoV-2 treated by Hydroxychloroquine<br>Blood sample on patients infected by SARS-CoV-2 treated by Hydroxychloroquine | Drug: Hydroxychloroquine (HCQ)<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of hydroxychloroquine (HCQ) | measured blood concentration by blood sample results. | Up to day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between hydroxychloroquine (HCQ) concentration and cardiac toxicity (QT interval) | measured by blood sample and electrocardiogram results. | Up to day 21 | 
| Correlation between Pharmacokinetic (concentration) and pharmacodynamic (viral load) of hydroxychloroquine (HCQ) | measured by blood sample | Day 1, Day 3, Day 5, Day 7, Day 14, Day 21 | 
| Pharmacokinetic model | Pharmacokinetic (area under the curve) analysis will be performed using a population approach with a non-linear mixed effects model. | Up to day 21 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, Hydroxychloroquine, COVID-19, Intensive care unit, Pharmacokinetics