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

Phase 3TerminatedNCT04522466

Centre Hospitalier Universitaire de Saint Etienne7 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Sars-CoV2

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (4)

Groupement Hospitalier des Portes de Province

Montélimar, France

Centre Hospitalier de Roanne

Roanne, France

CHU Saint-Etienne

Saint-Etienne, France

Clinique Mutualiste

Saint-Etienne, France

Outcomes

Primary Outcomes

Pharmacokinetics of hydroxychloroquine (HCQ)

measured blood concentration by blood sample results.

Time frame: Up to day 21

Secondary Outcomes

Correlation between hydroxychloroquine (HCQ) concentration and cardiac toxicity (QT interval)

measured by blood sample and electrocardiogram results.

Time frame: Up to day 21

Correlation between Pharmacokinetic (concentration) and pharmacodynamic (viral load) of hydroxychloroquine (HCQ)

measured by blood sample

Time frame: 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.

Time frame: Up to day 21