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

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 Overview

• Status: Terminated
• Conditions: Sars-CoV2
• Intervention / Treatment: Drug: Hydroxychloroquine (HCQ)

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Montélimar, France
    • Groupement Hospitalier des Portes de Province
  • Roanne, France
    • Centre hospitalier de Roanne
  • Saint-Étienne, France
    • CHU Saint-Etienne
  • Saint-Étienne, France
    • Clinique Mutualiste

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: CHU Saint-Etienne - Laboratoire de Pharmacologie - Toxicologie - Gaz du sang
• Investigators: Principal Investigator: Sophie PERINEL, MD, CHU Saint-Etienne

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2020
• Primary Completion (Actual): May 28, 2020
• Study Completion (Actual): May 28, 2020

Study Registration Dates

• First Submitted: August 19, 2020
• First Submitted That Met QC Criteria: August 20, 2020
• First Posted (Actual): August 21, 2020

Study Record Updates

• Last Update Posted (Actual): September 7, 2020
• Last Update Submitted That Met QC Criteria: September 4, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Pharmacokinetics; COVID-19; Intensive care unit; Hydroxychloroquine
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: 20CH065; 2020-001281-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No