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

Primary Purpose

COVID19, Hematologic Malignancy

Status
Withdrawn
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Hydroxychloroquine Sulfate 200 MG [Plaquenil]
Azithromycin 250 MG Oral Capsule
Placebo oral tablet
Placebo oral capsule
Sponsored by
Institut de cancérologie Strasbourg Europe
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID19 focused on measuring SARS-CoV-2, Hematologic malignancy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Institut de Cancérologie Strasbourg Europe

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Treatment arm

Control arm

Arm Description

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).

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Clinical evolution
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
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
Date and cause of death
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
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)
Evaluation of the seroconversion
Collection of serum to realize serological tests
NK immunological study
Phenotypic and functional study of NK lymphocytes at inclusion, Retrospective analysis on frozen cells.
Hospitalisation duration
Duration of hospitalisation (conventional, intensive care, reanimation)
Impact of the study treatment on the treatment of the hematological disease
Patient follow-up during 3 months : hematological status and associated therapy
Monitoring of the QT space
ECG (using connected machine to allow monitoring at home)
Dosage of residual concentration of azithromycine and hydroxychloroquine.
Dosage of residual concentration of azithromycine and hydroxychloroquine.
T immunological study
Phenotypic and functional study of T lymphocytes at inclusion, Retrospective analysis on frozen cells.

Full Information

First Posted
May 15, 2020
Last Updated
September 2, 2020
Sponsor
Institut de cancérologie Strasbourg Europe
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1. Study Identification

Unique Protocol Identification Number
NCT04392128
Brief Title
Study Evaluating the Efficacy of Hydroxychloroquine and Azithromycine in Patients With COVID-19 and Hematological Malignancies (HYACINTHE)
Acronym
HYACINTHE
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Withdrawn
Why Stopped
competent authority decision
Study Start Date
September 2, 2020 (Actual)
Primary Completion Date
September 2, 2020 (Actual)
Study Completion Date
September 2, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut de cancérologie Strasbourg Europe

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.
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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID19, Hematologic Malignancy
Keywords
SARS-CoV-2, Hematologic malignancy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment arm
Arm Type
Experimental
Arm Description
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).
Arm Title
Control arm
Arm Type
Placebo Comparator
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine Sulfate 200 MG [Plaquenil]
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Azithromycin 250 MG Oral Capsule
Intervention Description
Azithromycin is amacrolide antibiotic.
Intervention Type
Drug
Intervention Name(s)
Placebo oral tablet
Intervention Description
Placebo of Hydroxychloroquine Sulfate 200 MG [Plaquenil].
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Intervention Description
Placebo of Azithromycin capsules.
Primary Outcome Measure Information:
Title
Evaluation of the efficacy of hydroxychloroquine and azithromyncine on the viral load drop at day 5.
Description
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 Outcome Measure Information:
Title
Clinical evolution
Description
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
Title
Proportion of patients progressing to a severe form
Description
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
Title
Mortality
Description
Date and cause of death
Time Frame
up to 1 and 3 months
Title
Evaluation of viral load drop
Description
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
Title
Tolerance of study treatment
Description
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)
Time Frame
up to 3 months
Title
Evaluation of the seroconversion
Description
Collection of serum to realize serological tests
Time Frame
at inclusion, day 10, day 30 and day 90 after treatment
Title
NK immunological study
Description
Phenotypic and functional study of NK lymphocytes at inclusion, Retrospective analysis on frozen cells.
Time Frame
at day 10 and day 30 after treatment
Title
Hospitalisation duration
Description
Duration of hospitalisation (conventional, intensive care, reanimation)
Time Frame
up to 3 months
Title
Impact of the study treatment on the treatment of the hematological disease
Description
Patient follow-up during 3 months : hematological status and associated therapy
Time Frame
up to 3 months
Title
Monitoring of the QT space
Description
ECG (using connected machine to allow monitoring at home)
Time Frame
at inclusion, day 2, day 5, day 10
Title
Dosage of residual concentration of azithromycine and hydroxychloroquine.
Description
Dosage of residual concentration of azithromycine and hydroxychloroquine.
Time Frame
at day 5 and day 10
Title
T immunological study
Description
Phenotypic and functional study of T lymphocytes at inclusion, Retrospective analysis on frozen cells.
Time Frame
at day 10 and day 30 after treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Facility Information:
Facility Name
Institut de Cancérologie Strasbourg Europe
City
Strasbourg
ZIP/Postal Code
67033
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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