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

Sars-CoV2 Clinical Trial

— PREAVIS  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04522466
• Other study ID #: 20CH065
• Secondary ID: 2020-001281-11
• Status: Terminated
• Phase: Phase 3
• Start date: April 3, 2020
• Est. completion date: May 28, 2020

Study information

• Verified date: September 2020
• Source: Centre Hospitalier Universitaire de Saint Etienne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: May 28, 2020
• Est. primary completion date: May 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Sars-CoV2

Intervention

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).

Locations

Country	Name	City	State
France	Groupement Hospitalier des Portes de Province	Montélimar
France	Centre Hospitalier de Roanne	Roanne
France	CHU Saint-Etienne	Saint-Étienne
France	Clinique Mutualiste	Saint-Étienne

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Saint Etienne	CHU Saint-Etienne - Laboratoire de Pharmacologie - Toxicologie - Gaz du sang

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics of hydroxychloroquine (HCQ)	measured blood concentration by blood sample results.	Up to day 21
Secondary	Correlation between hydroxychloroquine (HCQ) concentration and cardiac toxicity (QT interval)	measured by blood sample and electrocardiogram results.	Up to day 21
Secondary	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
Secondary	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