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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Recruitment Status : Withdrawn (competent authority decision)
First Posted : May 18, 2020
Last Update Posted : September 4, 2020
Sponsor:
Information provided by (Responsible Party):
Institut de cancérologie Strasbourg Europe

Tracking Information
First Submitted Date  ICMJE May 15, 2020
First Posted Date  ICMJE May 18, 2020
Last Update Posted Date September 4, 2020
Actual Study Start Date  ICMJE September 2, 2020
Actual Primary Completion Date September 2, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2020)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 19, 2020)
  • 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)
  • 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
  • Mortality [ Time Frame: up to 1 and 3 months ]
    Date and cause of death
  • 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
  • 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)
  • Evaluation of the seroconversion [ Time Frame: at inclusion, day 10, day 30 and day 90 after treatment ]
    Collection of serum to realize serological tests
  • 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.
  • Hospitalisation duration [ Time Frame: up to 3 months ]
    Duration of hospitalisation (conventional, intensive care, reanimation)
  • 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
  • Monitoring of the QT space [ Time Frame: at inclusion, day 2, day 5, day 10 ]
    ECG (using connected machine to allow monitoring at home)
  • Dosage of residual concentration of azithromycine and hydroxychloroquine. [ Time Frame: at day 5 and day 10 ]
    Dosage of residual concentration of azithromycine and hydroxychloroquine.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2020)
  • 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)
  • 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
  • Mortality [ Time Frame: up to 1 and 3 months ]
    Date and cause of death
  • 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
  • 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)
  • Evaluation of the seroconversion [ Time Frame: at inclusion, day 10, day 30 and day 90 after treatment ]
    Collection of serum to realize serological tests
  • T and NK immunological study [ Time Frame: at day 10 and day 30 after treatment ]
    Phenotypic and functional study of T and NK lymphocytes at inclusion, Retrospective analysis on frozen cells.
  • Hospitalisation duration [ Time Frame: up to 3 months ]
    Duration of hospitalisation (conventional, intensive care, reanimation)
  • 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
  • Monitoring of the QT space [ Time Frame: at inclusion, day 1, day 5, day 10 ]
    ECG (using connected machine to allow monitoring at home)
  • Pharmacological study of the study treatment [ Time Frame: at day 5 and day 10 ]
    Dosage of residual concentration of azithromycine and hydroxychloroquine.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Evaluating the Efficacy of Hydroxychloroquine and Azithromycine in Patients With COVID-19 and Hematological Malignancies (HYACINTHE)
Official Title  ICMJE Randomised, Double-blind, Placebo-controlled Phase 2 Study Evaluating the Efficacy of Hydroxychloroquine and Azithromycine in Patients With COVID-19 and Hematological Malignancies
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)
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • COVID19
  • Hematologic Malignancy
Intervention  ICMJE
  • 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.
  • Drug: Placebo oral tablet
    Placebo of Hydroxychloroquine Sulfate 200 MG [Plaquenil].
  • Drug: Placebo oral capsule
    Placebo of Azithromycin capsules.
Study Arms  ICMJE
  • 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).
    Interventions:
    • Drug: Hydroxychloroquine Sulfate 200 MG [Plaquenil]
    • Drug: Azithromycin 250 MG Oral Capsule
  • 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)
    Interventions:
    • Drug: Placebo oral tablet
    • Drug: Placebo oral capsule
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: September 2, 2020)
0
Original Estimated Enrollment  ICMJE
 (submitted: May 15, 2020)
114
Actual Study Completion Date  ICMJE September 2, 2020
Actual Primary Completion Date September 2, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04392128
Other Study ID Numbers  ICMJE 2020-005
2020-002002-45 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Institut de cancérologie Strasbourg Europe
Study Sponsor  ICMJE Institut de cancérologie Strasbourg Europe
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Institut de cancérologie Strasbourg Europe
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP