Efficacy of Azithromycin-associated Hydroxychloroquine Therapy Given in General Practice in Early-stage Disease in COVID-19 Patients

NCT04371406 | Withdrawn Phase 3 DMC

• 2 other identifiers: APHP2004472020-001702-35
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Covid-19

Keywords

Covid-19; hydroxychloroquine; primary care; azithromycin

Outcome Measures

Primary Outcomes (2)

• 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

  between randomization and day14

• 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

  between day 0 and day 14

Secondary Outcomes (24)

• The all-cause mortality rate at day 14

  day 14

• The all-cause mortality rate at day 28

  day 28

• Rate of patients with occurrence of an unfavorable outcome between randomization and day 28

  between randomization and day 28

• The rate of use of mechanical ventilation at day 14

  day 14

• The rate of use of mechanical ventilation at day 28

  day 28

Study Arms (2)

Experimental Arm

EXPERIMENTAL

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

Drug: Hydroxychloroquine and Azithromycin

Control Arm

SHAM COMPARATOR

Dietetary supplement, Azinc form and vitality®, 2 capsules per day, for 10 days, in addition to standard of care

Dietary Supplement: Azinc

Interventions

Hydroxychloroquine and Azithromycin DRUG

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

Experimental Arm

Azinc DIETARY_SUPPLEMENT

Dietetary supplement, Azinc form and vitality®, 2 capsules per day, for 10 days, in addition to standard of care

Control Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

COVID-19

Interventions

Hydroxychloroquine; Azithromycin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Julie CHASTANG, Dr

  Department of General Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2020
• First Posted: May 1, 2020
• Study Start: April 1, 2020
• Primary Completion: August 1, 2020
• Study Completion: September 1, 2020
• Last Updated: October 27, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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
• Access Criteria: Researchers who provide a methodological sound proposal.