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

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ClinicalTrials.gov Identifier: NCT04392128
Recruitment Status : Not yet recruiting
First Posted : May 18, 2020
Last Update Posted : May 20, 2020
Sponsor:
Information provided by (Responsible Party):
Institut de Cancerologie 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.

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)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 114 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
Estimated Study Start Date : May 12, 2020
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : January 31, 2021


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.




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.



Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04392128


Contacts
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Contact: Valérie SARTORI 0368767223 ext 33 v.sartori@icans.eu
Contact: Manon VOEGELIN 0368767360 ext 33 m.voegelin@icans.eu

Locations
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France
Institut de Cancérologie Strasbourg Europe
Strasbourg, France, 67033
Contact: Valérie SARTORI    368767223 ext +33    v.sartoti@icans.eu   
Contact: Manon VOEGELIN    368767360 ext +33    m.voegelin@icans.eu   
Principal Investigator: Luc-Matthieu FORNECKER, MD-PhD         
Principal Investigator: Anne QUINQUENEL, MD         
Principal Investigator: Marie Thérèse RUBIO, MD-PhD         
Principal Investigator: Denis CAILLOT, MD         
Principal Investigator: Etienne DAGUINDAU, MD         
Principal Investigator: Stéphanie NGUYEN QUOC, MD-PhD         
Principal Investigator: Bernard DRENOU, MD         
Principal Investigator: Philippe CARASSOU, MD         
Sponsors and Collaborators
Institut de Cancerologie Strasbourg Europe
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Responsible Party: Institut de Cancerologie Strasbourg Europe
ClinicalTrials.gov Identifier: NCT04392128    
Other Study ID Numbers: 2020-005
2020-002002-45 ( EudraCT Number )
First Posted: May 18, 2020    Key Record Dates
Last Update Posted: May 20, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 Cancerologie Strasbourg Europe:
SARS-CoV-2
Hematologic malignancy
Additional relevant MeSH terms:
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Hematologic Neoplasms
Neoplasms
Neoplasms by Site
Hematologic Diseases
Azithromycin
Hydroxychloroquine
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents