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

Randomised, Double-blind, Placebo-controlled Phase 2 Study Evaluating the Efficacy of Hydroxychloroquine and Azithromycine in Patients With COVID-19 and Hematological Malignancies

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.

Study Overview

• Status: Withdrawn
• Conditions: Hematologic Malignancy; COVID19
• Intervention / Treatment: Drug: Hydroxychloroquine Sulfate 200 MG [Plaquenil]; Drug: Azithromycin 250 MG Oral Capsule; Drug: Placebo oral tablet; Drug: Placebo oral capsule

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)

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Strasbourg, France, 67033
    • Institut de cancerologie Strasbourg Europe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment arm; 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).	Drug: Hydroxychloroquine Sulfate 200 MG [Plaquenil]; 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.; Drug: Azithromycin 250 MG Oral Capsule; Azithromycin is amacrolide antibiotic.
Placebo Comparator: Control arm; 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)	Drug: Placebo oral tablet; Placebo of Hydroxychloroquine Sulfate 200 MG [Plaquenil].; Drug: Placebo oral capsule; Placebo of Azithromycin capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	5 days of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical evolution	Duration of fever - duration of respiratory symptoms (cough, dyspnea) - duration of other COVID-19 related symptoms (digestive symptoms, ageusia, anosmia)	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	up to 3 months
Mortality	Date and cause of death	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	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)	up to 3 months
Evaluation of the seroconversion	Collection of serum to realize serological tests	at inclusion, day 10, day 30 and day 90 after treatment
NK immunological study	Phenotypic and functional study of NK lymphocytes at inclusion, Retrospective analysis on frozen cells.	at day 10 and day 30 after treatment
Hospitalisation duration	Duration of hospitalisation (conventional, intensive care, reanimation)	up to 3 months
Impact of the study treatment on the treatment of the hematological disease	Patient follow-up during 3 months : hematological status and associated therapy	up to 3 months
Monitoring of the QT space	ECG (using connected machine to allow monitoring at home)	at inclusion, day 2, day 5, day 10
Dosage of residual concentration of azithromycine and hydroxychloroquine.	Dosage of residual concentration of azithromycine and hydroxychloroquine.	at day 5 and day 10
T immunological study	Phenotypic and functional study of T lymphocytes at inclusion, Retrospective analysis on frozen cells.	at day 10 and day 30 after treatment

Collaborators and Investigators

• Sponsor: Institut de cancérologie Strasbourg Europe

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2020
• Primary Completion (Actual): September 2, 2020
• Study Completion (Actual): September 2, 2020

Study Registration Dates

• First Submitted: May 15, 2020
• First Submitted That Met QC Criteria: May 15, 2020
• First Posted (Actual): May 18, 2020

Study Record Updates

• Last Update Posted (Actual): September 4, 2020
• Last Update Submitted That Met QC Criteria: September 2, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Hematologic malignancy
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Neoplasms by Site; Hematologic Diseases; Neoplasms; COVID-19; Hematologic Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Azithromycin; Hydroxychloroquine
• Other Study ID Numbers: 2020-005; 2020-002002-45 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No