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

COVID19 Clinical Trial

— 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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04392128
• Other study ID #: 2020-005
• Secondary ID: 2020-002002-45
• Status: Withdrawn
• Phase: Phase 2
• Start date: September 2, 2020
• Est. completion date: September 2, 2020

Study information

• Verified date: September 2020
• Source: Institut de Cancerologie Strasbourg Europe
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2, 2020
• Est. primary completion date: September 2, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID19
• Hematologic Malignancy
• Hematologic Neoplasms
• Neoplasms

Intervention

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.
• Azithromycin 250 MG Oral Capsule
Azithromycin is amacrolide antibiotic.
• Placebo oral tablet
Placebo of Hydroxychloroquine Sulfate 200 MG [Plaquenil].
• Placebo oral capsule
Placebo of Azithromycin capsules.

Locations

Country	Name	City	State
France	Institut de Cancérologie Strasbourg Europe	Strasbourg

Sponsors (1)

Lead Sponsor	Collaborator
Institut de Cancerologie Strasbourg Europe

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Mortality	Date and cause of death	up to 1 and 3 months
Secondary	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
Secondary	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
Secondary	Evaluation of the seroconversion	Collection of serum to realize serological tests	at inclusion, day 10, day 30 and day 90 after treatment
Secondary	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
Secondary	Hospitalisation duration	Duration of hospitalisation (conventional, intensive care, reanimation)	up to 3 months
Secondary	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
Secondary	Monitoring of the QT space	ECG (using connected machine to allow monitoring at home)	at inclusion, day 2, day 5, day 10
Secondary	Dosage of residual concentration of azithromycine and hydroxychloroquine.	Dosage of residual concentration of azithromycine and hydroxychloroquine.	at day 5 and day 10
Secondary	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