Clinical trial NCT04625218: Hydroxychloroquine for the Treatment of SARS-CoV2 (COVID 19) : Pharmacokinetic Study
Official title: Hydroxychloroquine for the Treatment of SARS-CoV2 (COVID 19) in the Critically Ill Patient: Pharmacokinetic Study. (CHLORO-VID)
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: COVID-19 Pneumonia
Keywords: SARS-CoV-2
hydroxychloroquine
pharmacokinetics
bronchoalveolar lavage fluid
Intensive Care Unit
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2020-11-12
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients hospitalized in intensive care

Brief summary: This study is a prospective, observational, open, monocentric multisite, pharmacokinetic study of hydroxychloroquine in critically ill patients. The aim of this study is to assess the pharmacokinetic behavior of hydroxychloroquine in COVID-19 critically ill patients treated with crushed hydroxychloroquine tablets (administered enterally using a nasogastric tube).

Detailed description: Based on the in vitro activity against SARS-CoV-2 and preliminary clinical data, hydroxychloroquine is currently used in the management of COVID-19 patients. In the meantime, the efficacy as well as the dosage of hydroxychloroquine is highly debated. Because of the severity of COVID-19 and the pharmacokinetics of hydroxychloroquine in systemic lupus erythematosus patients, a loading dose was rapidly included in the new hospital regimens to optimize drug distribution in tissues and more precisely in the lungs. Due to the lack of information on the plasma/blood concentrations required to induce a virological/clinical effect, plasma/blood concentration is monitored in many European countries for patients whether or not they are included in clinical research protocols. This problem of relationship between efficacy and exposure is important in the critically ill patient because both the bioavailability and the variability of the pharmacokinetic parameters are potentially responsible for variations in concentrations.

This study is a prospective, observational, open, multisite, pharmacokinetics study of hydroxychloroquine in critically ill patients. There is no supplemental intervention or additional samples compared to the standard care of these patients in our teaching hospital. The total duration of the study is that of the duration of hospitalization in intensive care. The duration of the pharmacokinetic study is 9 days, starting on D1 of the treatment with hydroxychloroquine, and ending with the last recommended residual plasma control. The total duration of treatment with hydroxychloroquine is 10 days, as recommended by the High Council of Public Health in its opinion of March 23, 2020.

Eligibility criteria: Inclusion Criteria:

* Patient ≥ 18 years old,
* Hospitalized in intensive care, intubated and ventilated
* With COVID-19 pneumonia confirmed by Rt-PCR,
* Having as specific treatment hydroxychloroquine, whatever the dosage regimen
* Having had the monitoring of the residual concentrations carried out by the Pharmacokinetics and Toxicology Laboratory of the Federative Institute of Biology of the Toulouse University Hospital the clinical Pharmacology and Toxicology laboratory of the Toulouse University Hospital
* Person affiliated to a social security scheme or equivalent

Exclusion Criteria:

* Minor patients
* Patients refusing to participate in the study
* Person participating in another research including an exclusion period still in progress.
* Contraindications to hydroxychloroquine: pre-existing retinopathy, known hypersensitivity to 4-aminoquinolines, hemolytic anemia, porphyria, G6PD deficiency, myasthenia gravis, association with citalopram, escitalopram, hydroxyzine, domperidone and piperaquine
* Patients undergoing treatment with medicines known to prolong the QT interval or likely to induce a cardiac arrhythmia such as for example anti-arrhythmics of class IA and III, tricyclic antidepressants and certain anti-infectives (in particular antibiotics of the family of macrolides and fluoroquinolones as well as trimethoprim-sulfamethoxazole).
* Pregnant or breastfeeding women

Primary outcomes:
measure: residual plasma concentration
timeFrame: Day 3
measure: residual plasma concentration
timeFrame: Day 5
measure: residual plasma concentration
timeFrame: Day 7
measure: residual plasma concentration
timeFrame: Day 9
Secondary outcomes:
measure: The number of days without artificial ventilation
timeFrame: Day 28
measure: The length of hospital stay in intensive care
timeFrame: Day 28
measure: Survival
timeFrame: Day 28
measure: Viral replication in the control bronchoalveolar lavage fluid on Day 7
timeFrame: Day 7
measure: Viral replication in the control bronchoalveolar lavage fluid on Day 14
timeFrame: Day 14
Other outcomes:
Locations:
city: Toulouse
country: France
facility: University Hospital of Toulouse
Study officials:
affiliation: University Hospital, Toulouse
name: Stéphanie RUIZ, PH
role: PRINCIPAL_INVESTIGATOR
References: