Clinical trial NCT04363060: Azithromycin+Amoxicillin/Clavulanate vs Amoxicillin/Clavulanate in COVID19 Patients With Pneumonia in Non-intensive Unit
Official title: Azithromycin With Amoxicillin/Clavulanate Versus Amoxicillin/Clavulanate Alone in COVID-19 Patients With Pneumonia and Hospitalized in a Non-intensive Care Unit Ward (AziA): a Superiority Open-label Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: COVID-19 Pneumonia
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2020-04-27
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Rate of positive SARS-CoV-2 RT-PCR
timeFrame: Day 6
Secondary outcomes:
measure: Rate of positive SARS-CoV-2 RT-PCR
timeFrame: Day 10
measure: Clinical evolution on the World Health Organization Ordinal Scale for Clinical Improvement for COVID-19
timeFrame: day 6, day 10, and day 30
measure: Total duration of antibiotic treatment during the 30 days following inclusion
timeFrame: 30 days
measure: Number of all-cause mortality during the 30 days following inclusion
timeFrame: 30 days
measure: Number of in-hospital mortality during the 30 days following inclusion
timeFrame: 30 days
measure: Number of patients transferred to intensive care unit during the 30-day follow-up
timeFrame: 30 days
measure: Number of days without mechanical ventilation during the 30 days following inclusion
timeFrame: 30 days
measure: adverse events attributable to antibiotic treatment during the 30 days following inclusion
timeFrame: 30 days
measure: Hospital length of stay during the 30 days following inclusion
timeFrame: 30 days
Other outcomes:
Locations:
city: Angers
country: France
facility: Chu Angers
city: La Roche-sur-Yon
country: France
facility: CHD Vendée
city: Poitiers
country: France
facility: CHU Poitiers
Study officials:
References: