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Azithromycin+Amoxicillin/Clavulanate vs Amoxicillin/Clavulanate in COVID19 Patients With Pneumonia in Non-intensive Unit

Phase 3
Conditions
COVID-19 Pneumonia
Interventions
Drug: amoxicillin/clavulanate
Combination Product: Azithromycin with amoxicillin/clavulanate
Registration Number
NCT04363060
Lead Sponsor
Nantes University Hospital
Brief Summary

The global pandemic of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, in December 2019, and has since spread worldwide.1 As of April 14, 2020, there have been more than 1.5 million reported cases and 124 000 deaths in more than 200 countries. A recent open-label nonrandomized French study reporte that addition of azithromycin to hydroxychloroquine in 6 patients resulted in numerically superior viral clearance (6/6, 100%) compared with hydroxychloroquine monotherapy (8/14, 57%) or control (2/16, 12.5%). Azithromycin alone has never been tested, whereas azithromycin has immunomodulating and anti-inflammatory properties that could theoretically prevent or limit secondary worsening. Our hypothesis is that azithromycin combined with amoxicillin/clavulanate will be superior to amoxicillin/clavulanate alone to obtain viral clearance at Day 6 in COVID-19 patients with pneumonia and hospitalized in a non-intensive care unit ward.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
104
Inclusion Criteria
  • Adult ≥ 18 ans,
  • Patient with positive SARS-CoV-2 RT-PCR on nasopharyngeal sample at randomization or within the previous 48 hours,
  • Patient with pneumonia diagnosed by thorax CT-scan or echography,
  • Patient able to take per os medication,
  • Written and signed consent of the patient,
  • Patients affiliated with or benefitting from a social security scheme.
Exclusion Criteria
  • Patient hospitalized in intensive care unit,
  • Patient who received more than 24 hours of antibiotic treatment for the ongoing episode,
  • Chronic renal failure with a Glomerular Filtration Rate < 20ml/min,
  • Severe hepatic failure,
  • Severe chronic cardiac insufficiency,
  • Allergy to macrolides,
  • Electrocardiogram showing corrected QT prolongation greater than 470 ms in men and 480 ms in women.
  • Life-threatening presentation expected to lead to possible imminent death (based on provider assessment)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Amoxicillin/clavulanateamoxicillin/clavulanateAmoxicillin/clavulanate every day during 7 days.
Azithromycin with amoxicillin/clavulanateAzithromycin with amoxicillin/clavulanateCombination of azithromycin during 4 days with amoxicillin/clavulanate during 7 days.
Primary Outcome Measures
NameTimeMethod
Rate of positive SARS-CoV-2 RT-PCRDay 6

Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal sample

Secondary Outcome Measures
NameTimeMethod
Number of all-cause mortality during the 30 days following inclusion30 days

Number of all-cause mortality during the 30 days following inclusion

Number of in-hospital mortality during the 30 days following inclusion30 days

Number of in-hospital mortality during the 30 days following inclusion

Number of patients transferred to intensive care unit during the 30-day follow-up30 days

Number of patients transferred to intensive care unit during the 30-day follow-up

Number of days without mechanical ventilation during the 30 days following inclusion30 days

Number of days without mechanical ventilation during the 30 days following inclusion

Rate of positive SARS-CoV-2 RT-PCRDay 10

Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal sample

Clinical evolution on the World Health Organization Ordinal Scale for Clinical Improvement for COVID-19day 6, day 10, and day 30

Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 score. Scale ranging from 0 to 8 (0:unifected; 8:dead)

Total duration of antibiotic treatment during the 30 days following inclusion30 days

Total duration of antibiotic treatment during the 30 days following inclusion

adverse events attributable to antibiotic treatment during the 30 days following inclusion30 days

adverse events attributable to antibiotic treatment during the 30 days following inclusion

Hospital length of stay during the 30 days following inclusion30 days

Hospital length of stay during the 30 days following inclusion

Trial Locations

Locations (3)

Chu Angers

🇫🇷

Angers, France

CHU Poitiers

🇫🇷

Poitiers, France

CHD Vendée

🇫🇷

La Roche-sur-Yon, France

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