Back to resultsEfficacy of Azithromycin-associated Hydroxychloroquine Therapy Given in General Practice in Early-stage Disease in COVID-19 Patients (MG-COVID)
Primary Purpose
Covid-19
Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Hydroxychloroquine and Azithromycin
Azinc
Sponsored by
About this trial
This is an interventional treatment trial for Covid-19 focused on measuring Covid-19, hydroxychloroquine, primary care, azithromycin
Eligibility Criteria
Inclusion Criteria:
- Inclusion criteria :
- Adult aged 18 to 75 years old
- Taken into primary health care for suspicion of early-stage COVID-19 infection (maximum 5 days of evolution). The patient must have presented within the previous 5 days at least one of the following criteria: fever (≥38°C), cough, anosmia, agueusia, diarrhea, headache, myalgia.
Criteria for randomization at D2 :
- Positive PCR on deep nasopharyngeal swab.
- Kalemia ≥ 3.5 mmol/L
- Normal magnesium and calcium levels (according to laboratory standards)
- QTc ≤ 460ms for women or QTc ≤ 450ms for men
- Beta-hCG negative
Exclusion criteria :
- Comorbidity(ies) or clinical condition of the patient requiring immediate oxygen therapy, hospitalization and/or ventilatory assistance
Concomitant treatment contraindicated, not recommended, or with precautions for use in combination with hydroxychloroquine or azithromycin:
- drug likely to induce torsades de pointe or at increased risk of ventricular arrhythmia, and in particular citalopram, escitalopram, hydroxyzine, domperidone, piperazine, class IA and III antiarrhythmics, tricyclic antidepressants, antipsychotics and certain anti-infectives (macrolides, fluoroquinolones).
- Alkaloids of ergot of rye, colchicine, cisapride
- proconvulsant or epileptogenic threshold lowering drugs: imipraminic antidepressants, selective serotonin reuptake inhibitors, neuroleptics (phenothiazines and butyrophenones) and tramadol.
- Known history of contraindications or increased risk of treatment with hydroxychloroquine or azithromycin (retinopathy,renal failure, significant liver failure, severe cholestasis, porphyria, known G6PD deficit, hypomagnesemia and hypokalemia, diabetes, myasthenia gravis, Heart diseases (heart failure, infarction, arrhythmia, congenital QTc prolongation, abnormalities that interfere with QTc measurement such as Left Bundle Branch Block, Right Bundle Branch Block, Pace maker with ventricular pacing), epilepsy, allergy to hydroxychloroquine, chloroquine, azithromycin, erythromycin, any other macrolide, ketolide or any of the excipients of Plaquenil® or Zithromax® or any of the components of Azinc form and vitality®.
- Ongoing treatment with hydroxychloroquine or azithromycin, regardless of the indication.
- Taking other antiviral targeted therapy used in COVID-19 disease
- Women who are pregnant or breastfeeding or planning to become pregnant within 8 months of discontinuing hydroxychloroquine therapy.
- No National Health Insurrance (sécurité sociale, CMU or AME) coverage.
- Major under guardianship or curatorship
- Participation in another therapeutic clinical trial for COVID-19
- Refusal to participate in the study and/or lack of signature of a consent
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Experimental Arm
Control Arm
Arm Description
Hydroxychloroquine sulfate (PLAQUENIL®), 200mg x 3 /d, for 10 days AND Azithromycin (ZITHROMAX®), 500mg on D1 and then 250mg/d for the next 4 days, in addition to standard of care
Dietetary supplement, Azinc form and vitality®, 2 capsules per day, for 10 days, in addition to standard of care
Outcomes
Primary Outcome Measures
Rate of patients with occurrence of an unfavorable outcome between randomization and day 14
Unfavorable outcome defined by the onset of at least one of the following between randomization and day 14: hospitalization, death or percutaneous O² saturation ≤ 92% in ambient air
Primary outcome of ancillary virological study : evolution of viral load between day 0 and day 14
Ancillary virological study : evolution of viral load between day 0 and day 14, measured by the threshold cycle,Ct, with PCR on naso-pharyngeal swab
Secondary Outcome Measures
The all-cause mortality rate at day 14
The all-cause mortality rate at day 28
Rate of patients with occurrence of an unfavorable outcome between randomization and day 28
Unfavorable outcome defined by the onset of at least one of the following between randomization and day 28: hospitalization, death or percutaneous O² saturation ≤ 92% in ambient air
The rate of use of mechanical ventilation at day 14
The rate of use of mechanical ventilation at day 28
The Intensive Care Unit admission rate at day 14
The Intensive Care Unit admission rate at day 28
Number of days of hospitalization for any cause between day 0 and day 14
Number of days of hospitalization for any cause between day 0 and day 28
The time to resolution of all COVID symptoms at day 14
Time to resolution of all COVID-19 symptoms : no COVID symptom for at least 48 hours without symptomatic treatment in previous 24 hours
The time to resolution of all COVID symptoms atday 28
Time to resolution of all COVID-19 symptoms : no COVID symptom for at least 48 hours without symptomatic treatment in previous 24 hours
The rate of use of oxygen therapy at day 14
The rate of use of oxygen therapy at day 28
The rate of use of secondary antibiotic therapy (after day 2) at day 14
The rate of use of secondary antibiotic therapy (after day 2) at day 28
Clinical status at day 14
Clinical status on a 7-point ordinal scale :
Not hospitalized, no limitations on activities
Not hospitalized, limitation on activities;
Hospitalized, not requiring supplemental oxygen;
Hospitalized, requiring supplemental oxygen;
Hospitalized, on non-invasive ventilation or high flow oxygen devices;
Hospitalized, on invasive mechanical ventilation or ECMO;
Death.
Clinical status at day 28
Clinical status on a 7-point ordinal scale :
Not hospitalized, no limitations on activities
Not hospitalized, limitation on activities;
Hospitalized, not requiring supplemental oxygen;
Hospitalized, requiring supplemental oxygen;
Hospitalized, on non-invasive ventilation or high flow oxygen devices;
Hospitalized, on invasive mechanical ventilation or ECMO;
Death.
number of serious adverse events at day 14
number serious adverse events at day 28
number of adverse events at day 14
number of adverse events at day 28
The rate of patients with treatment withdrawal
Ancillary virological study : rate of patients with negative viral load at day 8
Ancillary virological study : rate of patients with negative viral load at PCR on naso pharyngeal swab at day 8
Ancillary virological study : rate of patients with negative viral load at day 14
Ancillary virological study : rate of patients with negative viral load at PCR on naso pharyngeal swab at day 14
Full Information
NCT ID
NCT04371406
First Posted
April 29, 2020
Last Updated
October 23, 2020
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT04371406
Brief Title
Efficacy of Azithromycin-associated Hydroxychloroquine Therapy Given in General Practice in Early-stage Disease in COVID-19 Patients
Acronym
MG-COVID
Official Title
Efficacy of Azithromycin-associated Hydroxychloroquine Therapy Given in General Practice in Early-stage Disease in COVID-19 Patients: Randomized Controlled Trial: MG-COVID
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Regulatory approvals have not been obtained
Study Start Date
April 2020 (Anticipated)
Primary Completion Date
August 2020 (Anticipated)
Study Completion Date
September 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Hydroxychloroquine, a derivative of chloroquine (an antimalarial drug) with a weak immunosuppressive effect, is prescribed by some teams alone or in combination with azithromycin. No randomized controlled trials have demonstrated its efficacy, particularly in primary care in the early stages of the disease. However, currently available data suggest better efficacy if treatment is given early in the disease, before symptoms worsen. To date, the majority of COVID-19 patients treated in outpatient care, particularly in general practice, represent the majority of COVID-19 patients.
It is essential to evaluate, in primary care, the efficacy and safety of hydroxychloroquine combined with azithromycin in Covid-19 patients in order to be able to implement this therapeutic strategy as soon as the first symptoms appear. We realize a randomized, controlled, open superiority trial, in 2 parallel groups (ratio 1:1).The main objective is to assess the efficacy of Hydroxychloroquine combined with azithromycin in COVID-19 patients in primary care, in add-on to standard of care, on unfavorable outcome defined by the onset of at least one of the following between D0 and D14: hospitalization, death or percutaneous O² saturation ≤ 92% in ambient air.
Detailed Description
Randomized, controlled, open superiority trial, in 2 parallel groups (ratio 1:1).
Eligible consecutive patient will be offered to take part in the trial during a visit to thier GP for COVID symptoms. After verification of eligibility criteria and written informed consent, a nasopharyngeal swab, an ECG and a blood sampled (kalaemia, magnesemia and calcemia) will be performed.
Patient with SARS-CoV-2 PCR positive result and still fulfilling eligibility criteria will be randomized on day2 (D2) through a web-based allocation system, following a computer generated allocation list, stratified on center and existence of any comorbidity, to experimental or control group. Patients without confirmation of SARS-CoV-2 infection on PCR will not continue the trial. Both groups patients will have a paper-based diary to record their daily symptoms and drug intake. A clinical follow-up will be done by the GP at D5, D8, D14 and D28.The main analysis population will be in intention to treat. An intermediate efficacy analysis is planned when 50% of patients have reached D14.
Two hundred consecutive patients (from pre-identified centers) will be included in an ancillary virological study to assess evolution of viral load at D8 and D14. For these patients all nasopharyngeal swab will be sent to a centralised lab at Pitié-Salpêtrière Hospital.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid-19
Keywords
Covid-19, hydroxychloroquine, primary care, azithromycin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Experimental Arm
Arm Type
Experimental
Arm Description
Hydroxychloroquine sulfate (PLAQUENIL®), 200mg x 3 /d, for 10 days AND Azithromycin (ZITHROMAX®), 500mg on D1 and then 250mg/d for the next 4 days, in addition to standard of care
Arm Title
Control Arm
Arm Type
Sham Comparator
Arm Description
Dietetary supplement, Azinc form and vitality®, 2 capsules per day, for 10 days, in addition to standard of care
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine and Azithromycin
Intervention Description
Hydroxychloroquine sulfate (PLAQUENIL®), 200mg x 3 /d, for 10 days AND Azithromycin (ZITHROMAX®), 500mg on D1 and then 250mg/d for the next 4 days, in addition to standard of care
Intervention Type
Dietary Supplement
Intervention Name(s)
Azinc
Intervention Description
Dietetary supplement, Azinc form and vitality®, 2 capsules per day, for 10 days, in addition to standard of care
Primary Outcome Measure Information:
Title
Rate of patients with occurrence of an unfavorable outcome between randomization and day 14
Description
Unfavorable outcome defined by the onset of at least one of the following between randomization and day 14: hospitalization, death or percutaneous O² saturation ≤ 92% in ambient air
Time Frame
between randomization and day14
Title
Primary outcome of ancillary virological study : evolution of viral load between day 0 and day 14
Description
Ancillary virological study : evolution of viral load between day 0 and day 14, measured by the threshold cycle,Ct, with PCR on naso-pharyngeal swab
Time Frame
between day 0 and day 14
Secondary Outcome Measure Information:
Title
The all-cause mortality rate at day 14
Time Frame
day 14
Title
The all-cause mortality rate at day 28
Time Frame
day 28
Title
Rate of patients with occurrence of an unfavorable outcome between randomization and day 28
Description
Unfavorable outcome defined by the onset of at least one of the following between randomization and day 28: hospitalization, death or percutaneous O² saturation ≤ 92% in ambient air
Time Frame
between randomization and day 28
Title
The rate of use of mechanical ventilation at day 14
Time Frame
day 14
Title
The rate of use of mechanical ventilation at day 28
Time Frame
day 28
Title
The Intensive Care Unit admission rate at day 14
Time Frame
day 14
Title
The Intensive Care Unit admission rate at day 28
Time Frame
day 28
Title
Number of days of hospitalization for any cause between day 0 and day 14
Time Frame
between randomization and day 14
Title
Number of days of hospitalization for any cause between day 0 and day 28
Time Frame
between randomization and day 28
Title
The time to resolution of all COVID symptoms at day 14
Description
Time to resolution of all COVID-19 symptoms : no COVID symptom for at least 48 hours without symptomatic treatment in previous 24 hours
Time Frame
day 14
Title
The time to resolution of all COVID symptoms atday 28
Description
Time to resolution of all COVID-19 symptoms : no COVID symptom for at least 48 hours without symptomatic treatment in previous 24 hours
Time Frame
day 28
Title
The rate of use of oxygen therapy at day 14
Time Frame
between randomization and day 14
Title
The rate of use of oxygen therapy at day 28
Time Frame
between randomization and day 28
Title
The rate of use of secondary antibiotic therapy (after day 2) at day 14
Time Frame
between randomization and day 14
Title
The rate of use of secondary antibiotic therapy (after day 2) at day 28
Time Frame
between randomization and day 28
Title
Clinical status at day 14
Description
Clinical status on a 7-point ordinal scale :
Not hospitalized, no limitations on activities
Not hospitalized, limitation on activities;
Hospitalized, not requiring supplemental oxygen;
Hospitalized, requiring supplemental oxygen;
Hospitalized, on non-invasive ventilation or high flow oxygen devices;
Hospitalized, on invasive mechanical ventilation or ECMO;
Death.
Time Frame
day 14
Title
Clinical status at day 28
Description
Clinical status on a 7-point ordinal scale :
Not hospitalized, no limitations on activities
Not hospitalized, limitation on activities;
Hospitalized, not requiring supplemental oxygen;
Hospitalized, requiring supplemental oxygen;
Hospitalized, on non-invasive ventilation or high flow oxygen devices;
Hospitalized, on invasive mechanical ventilation or ECMO;
Death.
Time Frame
day 28
Title
number of serious adverse events at day 14
Time Frame
day 14
Title
number serious adverse events at day 28
Time Frame
day 28
Title
number of adverse events at day 14
Time Frame
day 14
Title
number of adverse events at day 28
Time Frame
day 28
Title
The rate of patients with treatment withdrawal
Time Frame
day 14
Title
Ancillary virological study : rate of patients with negative viral load at day 8
Description
Ancillary virological study : rate of patients with negative viral load at PCR on naso pharyngeal swab at day 8
Time Frame
day 8
Title
Ancillary virological study : rate of patients with negative viral load at day 14
Description
Ancillary virological study : rate of patients with negative viral load at PCR on naso pharyngeal swab at day 14
Time Frame
day 14
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Inclusion criteria :
Adult aged 18 to 75 years old
Taken into primary health care for suspicion of early-stage COVID-19 infection (maximum 5 days of evolution). The patient must have presented within the previous 5 days at least one of the following criteria: fever (≥38°C), cough, anosmia, agueusia, diarrhea, headache, myalgia.
Criteria for randomization at D2 :
Positive PCR on deep nasopharyngeal swab.
Kalemia ≥ 3.5 mmol/L
Normal magnesium and calcium levels (according to laboratory standards)
QTc ≤ 460ms for women or QTc ≤ 450ms for men
Beta-hCG negative
Exclusion criteria :
Comorbidity(ies) or clinical condition of the patient requiring immediate oxygen therapy, hospitalization and/or ventilatory assistance
Concomitant treatment contraindicated, not recommended, or with precautions for use in combination with hydroxychloroquine or azithromycin:
drug likely to induce torsades de pointe or at increased risk of ventricular arrhythmia, and in particular citalopram, escitalopram, hydroxyzine, domperidone, piperazine, class IA and III antiarrhythmics, tricyclic antidepressants, antipsychotics and certain anti-infectives (macrolides, fluoroquinolones).
Alkaloids of ergot of rye, colchicine, cisapride
proconvulsant or epileptogenic threshold lowering drugs: imipraminic antidepressants, selective serotonin reuptake inhibitors, neuroleptics (phenothiazines and butyrophenones) and tramadol.
Known history of contraindications or increased risk of treatment with hydroxychloroquine or azithromycin (retinopathy,renal failure, significant liver failure, severe cholestasis, porphyria, known G6PD deficit, hypomagnesemia and hypokalemia, diabetes, myasthenia gravis, Heart diseases (heart failure, infarction, arrhythmia, congenital QTc prolongation, abnormalities that interfere with QTc measurement such as Left Bundle Branch Block, Right Bundle Branch Block, Pace maker with ventricular pacing), epilepsy, allergy to hydroxychloroquine, chloroquine, azithromycin, erythromycin, any other macrolide, ketolide or any of the excipients of Plaquenil® or Zithromax® or any of the components of Azinc form and vitality®.
Ongoing treatment with hydroxychloroquine or azithromycin, regardless of the indication.
Taking other antiviral targeted therapy used in COVID-19 disease
Women who are pregnant or breastfeeding or planning to become pregnant within 8 months of discontinuing hydroxychloroquine therapy.
No National Health Insurrance (sécurité sociale, CMU or AME) coverage.
Major under guardianship or curatorship
Participation in another therapeutic clinical trial for COVID-19
Refusal to participate in the study and/or lack of signature of a consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julie CHASTANG, Dr
Organizational Affiliation
Department of General Medicine
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Data are available upon reasonable request. The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.
Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.
IPD Sharing Time Frame
Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
IPD Sharing Access Criteria
Researchers who provide a methodological sound proposal.
Learn more about this trial
Efficacy of Azithromycin-associated Hydroxychloroquine Therapy Given in General Practice in Early-stage Disease in COVID-19 Patients
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