Clinical trial NCT04392128: Study Evaluating the Efficacy of Hydroxychloroquine and Azithromycine in Patients With COVID-19 and Hematological Malignancies (HYACINTHE)
Official title: Randomised, Double-blind, Placebo-controlled Phase 2 Study Evaluating the Efficacy of Hydroxychloroquine and Azithromycine in Patients With COVID-19 and Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: COVID19
Hematologic Malignancy
Keywords: SARS-CoV-2
Hematologic malignancy
Lead sponsor: Institut de cancérologie Strasbourg Europe
Sponsor class: OTHER
First posted: 2020-05-18
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Evaluation of the efficacy of hydroxychloroquine and azithromyncine on the viral load drop at day 5.
timeFrame: 5 days of treatment
Secondary outcomes:
measure: Clinical evolution
timeFrame: up to 3 months
measure: Proportion of patients progressing to a severe form
timeFrame: up to 3 months
measure: Mortality
timeFrame: up to 1 and 3 months
measure: Evaluation of viral load drop
timeFrame: at day 10
measure: Tolerance of study treatment
timeFrame: up to 3 months
measure: Evaluation of the seroconversion
timeFrame: at inclusion, day 10, day 30 and day 90 after treatment
measure: NK immunological study
timeFrame: at day 10 and day 30 after treatment
measure: Hospitalisation duration
timeFrame: up to 3 months
measure: Impact of the study treatment on the treatment of the hematological disease
timeFrame: up to 3 months
measure: Monitoring of the QT space
timeFrame: at inclusion, day 2, day 5, day 10
measure: Dosage of residual concentration of azithromycine and hydroxychloroquine.
timeFrame: at day 5 and day 10
measure: T immunological study
timeFrame: at day 10 and day 30 after treatment
Other outcomes:
Locations:
city: Strasbourg
country: France
facility: Institut de Cancérologie Strasbourg Europe
Study officials:
References: