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).
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.
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
University Hospital of Toulouse
Toulouse, France
Stéphanie RUIZ, PH, Principal Investigator
University Hospital, Toulouse