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

• ClinicalTrials.gov Identifier: NCT04392128
• Recruitment Status: Withdrawn
• First Posted: May 18, 2020
• Last Update Posted: September 4, 2020
• Sponsor: Institut de cancérologie Strasbourg Europe
• Information provided by (Responsible Party): Institut de cancérologie Strasbourg Europe

Study Description

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.

Condition or disease	Intervention/treatment	Phase
COVID19; Hematologic Malignancy	Drug: Hydroxychloroquine Sulfate 200 MG [Plaquenil]; Drug: Azithromycin 250 MG Oral Capsule; Drug: Placebo oral tablet; Drug: Placebo oral capsule	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 2, 2020
• Actual Primary Completion Date: September 2, 2020
• Actual Study Completion Date: September 2, 2020

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Evaluation of the efficacy of hydroxychloroquine and azithromyncine on the viral load drop at day 5. [ Time Frame: 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 :

1. Clinical evolution [ Time Frame: up to 3 months ]
   Duration of fever - duration of respiratory symptoms (cough, dyspnea) - duration of other COVID-19 related symptoms (digestive symptoms, ageusia, anosmia)
2. Proportion of patients progressing to a severe form [ Time Frame: 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
3. Mortality [ Time Frame: up to 1 and 3 months ]
   Date and cause of death
4. Evaluation of viral load drop [ Time Frame: 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
5. Tolerance of study treatment [ Time Frame: 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)
6. Evaluation of the seroconversion [ Time Frame: at inclusion, day 10, day 30 and day 90 after treatment ]
   Collection of serum to realize serological tests
7. NK immunological study [ Time Frame: at day 10 and day 30 after treatment ]
   Phenotypic and functional study of NK lymphocytes at inclusion, Retrospective analysis on frozen cells.
8. Hospitalisation duration [ Time Frame: up to 3 months ]
   Duration of hospitalisation (conventional, intensive care, reanimation)
9. Impact of the study treatment on the treatment of the hematological disease [ Time Frame: up to 3 months ]
   Patient follow-up during 3 months : hematological status and associated therapy
10. Monitoring of the QT space [ Time Frame: at inclusion, day 2, day 5, day 10 ]
    ECG (using connected machine to allow monitoring at home)
11. Dosage of residual concentration of azithromycine and hydroxychloroquine. [ Time Frame: at day 5 and day 10 ]
    Dosage of residual concentration of azithromycine and hydroxychloroquine.
12. T immunological study [ Time Frame: at day 10 and day 30 after treatment ]
    Phenotypic and functional study of T lymphocytes at inclusion, Retrospective analysis on frozen cells.

Eligibility Criteria

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

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

Contacts and Locations

Locations

France

Institut de Cancérologie Strasbourg Europe

Strasbourg, France, 67033

Sponsors and Collaborators

Institut de cancérologie Strasbourg Europe

More Information

• Responsible Party: Institut de cancérologie Strasbourg Europe
• ClinicalTrials.gov Identifier: NCT04392128
• Other Study ID Numbers: 2020-005; 2020-002002-45 ( EudraCT Number )
• First Posted: May 18, 2020
• Last Update Posted: September 4, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Institut de cancérologie Strasbourg Europe:

SARS-CoV-2; Hematologic malignancy

Additional relevant MeSH terms:

COVID-19; Coronavirus Infections; Coronaviridae Infections; Hydroxychloroquine; Neoplasms; Hematologic Neoplasms; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Neoplasms by Site; Hematologic Diseases; Azithromycin; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents