Study Evaluating the Efficacy of Hydroxychloroquine and Azithromycine in Patients With COVID-19 and Hematological Malignancies (HYACINTHE)

Institut de cancérologie Strasbourg Europe

Overview

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.

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)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Conditions

COVID19 Hematologic Malignancy

Interventions

Hydroxychloroquine Sulfate 200 MG [Plaquenil]DRUG

Hydroxychloroquine is an anti-malarial drug also used as anti-inflammatory treatment for systemic lupus erythematosus and rheumatic disorders. HCQ also inhibits pH-dependant replication stages of diverse types of viruses including flavivirus, retrovirus and coronaviruses.

Azithromycin 250 MG Oral CapsuleDRUG

Azithromycin is amacrolide antibiotic.

Placebo oral tabletDRUG

Placebo of Hydroxychloroquine Sulfate 200 MG \[Plaquenil\].

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Institut de Cancérologie Strasbourg Europe

Strasbourg, France

Outcomes

Primary Outcomes

Evaluation of the efficacy of hydroxychloroquine and azithromyncine on the viral load drop at day 5.

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.

Time frame: 5 days of treatment

Secondary Outcomes

Clinical evolution

Duration of fever - duration of respiratory symptoms (cough, dyspnea) - duration of other COVID-19 related symptoms (digestive symptoms, ageusia, anosmia)

Time frame: up to 3 months

Proportion of patients progressing to a severe form

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

Time frame: up to 3 months

Mortality

Date and cause of death

Time frame: up to 1 and 3 months

Evaluation of viral load drop

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

Time frame: at day 10

Tolerance of study treatment

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)

Data from ClinicalTrials.gov

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