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

Phase 3

Terminated

• Conditions: Sars-CoV2
• Interventions: Drug: Hydroxychloroquine (HCQ)

• Registration Number: NCT04522466
• Lead Sponsor: Centre Hospitalier Universitaire de Saint Etienne

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-04-03
• Primary Completion: 2020-05-28
• Study Completion: 2020-05-28
• Study First Submitted: 2020-08-19
• Study First Submitted QC: 2020-08-20
• Study First Posted: 2020-08-21
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-04
• Last Update Posted: 2020-09-07

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 7

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Patients infected by SARS-CoV-2 treated by Hydroxychloroquine	Hydroxychloroquine (HCQ)	Blood sample on patients infected by SARS-CoV-2 treated by Hydroxychloroquine

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics of hydroxychloroquine (HCQ)	Up to day 21	measured blood concentration by blood sample results.

Secondary Outcome Measures

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

Trial Locations

Locations (4)

Groupement Hospitalier des Portes de Province; 🇫🇷 Montélimar, France

CHU Saint-Etienne; 🇫🇷 Saint-Étienne, France

Clinique Mutualiste; 🇫🇷 Saint-Étienne, France

Centre Hospitalier de Roanne; 🇫🇷 Roanne, France