Study Evaluating the Efficacy of Hydroxychloroquine and Azithromycine in Patients With COVID-19 and Hematological Malignancies (HYACINTHE)
- Conditions
- COVID19Hematologic Malignancy
- Interventions
- Drug: Placebo oral tabletDrug: Placebo oral capsule
- Registration Number
- NCT04392128
- Lead Sponsor
- Institut de cancérologie Strasbourg Europe
- Brief Summary
The primary objective of this phase 2, multicentric, placebo-controlled double-blind, randomized study is to evaluate the efficacy of the combination of hydroxychloroquine and azithromycine on the viral load drop at day 5 among patients with COVID-19 and hematological malignancies.
- Detailed Description
The study will evaluate the effect of the combination of hydroxychloroquine and azithromycine versus placebo among 114 patients with COVID-19 and hematologic malignancy.
After randomization in 1:1 ratio, patients will receive either the study treatment or placebo :
* Patients enrolled in the experimental arm will receive hydroxychloroquine (200mgx3 tablets per day during 10 days) and azithromycine (500 mg at day 1 then 250mg per day during 4 days)
* Patients enrolled in the control arm will receive a placebo of hydroxychloroquine (3 tablets per day during 10 days) and a placebo of azithromycine (2 capsules at day 1, then 1 capsule per day during 4 days)
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 18 years or older patients
- Patient with hematologic malignancy who received or not hematopoietic stem cell transplantation
- Non severe Covid-19 disease
- PCR-confirmed COVID-19 disease by a nasopharyngeal swab
- Life-expectancy related to the hematologic malignancy of at least 1 month
- Men or women of child-bearing potential accepting to use effective contraception during and until 8 months after the end of the study treatment
- Patients with severe form of COVID-19 infection defined as the presence of crackles observed during clinical exam, associated with less than 94% oxygen saturation or patients with respiratory insufficiency on oxygen therapy or mechanical ventilation
- Previous treatment with hydroxychloroquine or azithromycine for Covid-19 infection
- QTc interval greater than 480 ms
- Hypersensibility to hydroxychloroquine or azithromycine
- Retinopathy
- TGO or TGP geater than 5 x the normal upper limit
- Creatinine clearance lower than 30 ml/min
- Concomitant treatment that may lead to prolongation of the QT space
- Concomitant treatment with dihydroergotamine, ergotamine, cisapride or colchicine
- Known G6PD deficiency
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment arm Hydroxychloroquine Sulfate 200 MG [Plaquenil] Patients enrolled in the experimental arm will receive hydroxychloroquine (200mgx3 tablets per day during 10 days) and azithromycine (500 mg at day 1 (2 capsules taken at the same time) then 250mg per day (1 capsule per day) during 4 days). Control arm Placebo oral tablet Patients enrolled in the control arm will receive a placebo of hydroxychloroquine (3 tablets per day during 10 days) and a placebo of azithromycine (2 capsules taken at the same time at day 1, then 1 capsule per day during 4 days) Control arm Placebo oral capsule Patients enrolled in the control arm will receive a placebo of hydroxychloroquine (3 tablets per day during 10 days) and a placebo of azithromycine (2 capsules taken at the same time at day 1, then 1 capsule per day during 4 days) Treatment arm Azithromycin 250 MG Oral Capsule Patients enrolled in the experimental arm will receive hydroxychloroquine (200mgx3 tablets per day during 10 days) and azithromycine (500 mg at day 1 (2 capsules taken at the same time) then 250mg per day (1 capsule per day) during 4 days).
- Primary Outcome Measures
Name Time Method Evaluation of the efficacy of hydroxychloroquine and azithromyncine on the viral load drop at day 5. 5 days of treatment Locally evaluated rate of viral response. Favorable response is defined as (1) complete response : negative PCR (absence of detectable signal with a minimum of 40 cycles) or (2) major response : detectable signal but with an increased number of cycles \> or egal to 10 compared to initial PCR. Response failure is defined as (1) minor response : detectable signal but with an increased number of cycles \< 10 compared to initial PCR or (2) stabilisation or worsening of the viral load.
- Secondary Outcome Measures
Name Time Method Dosage of residual concentration of azithromycine and hydroxychloroquine. at day 5 and day 10 Dosage of residual concentration of azithromycine and hydroxychloroquine.
Mortality up to 1 and 3 months Date and cause of death
Evaluation of the seroconversion at inclusion, day 10, day 30 and day 90 after treatment Collection of serum to realize serological tests
Impact of the study treatment on the treatment of the hematological disease up to 3 months Patient follow-up during 3 months : hematological status and associated therapy
Clinical evolution up to 3 months Duration of fever - duration of respiratory symptoms (cough, dyspnea) - duration of other COVID-19 related symptoms (digestive symptoms, ageusia, anosmia)
Proportion of patients progressing to a severe form up to 3 months Less or equal to 94% oxygen saturation - need to initiate oxygenotherapy - occurrence of respiratory distress - patient transfer in intensive care unit - need of mechanical ventilation - occurrence of non-respiratory organ failure - occurrence of septic shock
Evaluation of viral load drop at day 10 SARS-CoV-2 viral load by PCR on nasopharyngeal swab at day 10 (if positive at day 5) : rate of negativation and comparison of number of cycles with previous samples
Tolerance of study treatment up to 3 months Frequence and causality of all-grade cardiac adverse events - frequence and causality of grade \> 1 adverse events for other adverse events - frequence and causality of serious adverse events (CTCAE v5)
NK immunological study at day 10 and day 30 after treatment Phenotypic and functional study of NK lymphocytes at inclusion, Retrospective analysis on frozen cells.
Hospitalisation duration up to 3 months Duration of hospitalisation (conventional, intensive care, reanimation)
Monitoring of the QT space at inclusion, day 2, day 5, day 10 ECG (using connected machine to allow monitoring at home)
T immunological study at day 10 and day 30 after treatment Phenotypic and functional study of T lymphocytes at inclusion, Retrospective analysis on frozen cells.
Trial Locations
- Locations (1)
Institut de Cancérologie Strasbourg Europe
🇫🇷Strasbourg, France
Institut de Cancérologie Strasbourg Europe🇫🇷Strasbourg, France