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

COVID-19 Pneumonia Clinical Trial

— AziA  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04363060
• Other study ID #: RC20_0168
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: April 30, 2020
• Est. completion date: July 30, 2020

Study information

• Verified date: April 2020
• Source: Nantes University Hospital
• Contact: Emmanuel MONTASSIER
• Phone: +33 (0)2 53 48 20 38
• Email: Emmanuel.montassier[@]chu-nantes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 104
• Est. completion date: July 30, 2020
• Est. primary completion date: July 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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)

Related Conditions & MeSH terms

• COVID-19 Pneumonia
• Pneumonia

Intervention

Combination Product:
• Azithromycin with amoxicillin/clavulanate
Patients will receive azithromycin 500 mg on day 1 followed by 250mg per day for the next four days with amoxicillin/clavulanate 1 gr 3 times per day during 7 days. In case of allergy, amoxicillin/clavulanate can be replaced by a third-generation cephalosporin

Drug:
• amoxicillin/clavulanate
Patients will receive amoxicillin/clavulanate 1 gr 3 times per day during 7 days. In case of allergy, amoxicillin/clavulanate can be replaced by a third-generation cephalosporin

Locations

Country	Name	City	State
France	Chu Angers	Angers
France	CHD Vendée	La Roche-sur-Yon
France	CHU Poitiers	Poitiers

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of positive SARS-CoV-2 RT-PCR	Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal sample	Day 6
Secondary	Rate of positive SARS-CoV-2 RT-PCR	Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal sample	Day 10
Secondary	Clinical evolution on the World Health Organization Ordinal Scale for Clinical Improvement for COVID-19	Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 score. Scale ranging from 0 to 8 (0:unifected; 8:dead)	day 6, day 10, and day 30
Secondary	Total duration of antibiotic treatment during the 30 days following inclusion	Total duration of antibiotic treatment during the 30 days following inclusion	30 days
Secondary	Number of all-cause mortality during the 30 days following inclusion	Number of all-cause mortality during the 30 days following inclusion	30 days
Secondary	Number of in-hospital mortality during the 30 days following inclusion	Number of in-hospital mortality during the 30 days following inclusion	30 days
Secondary	Number of patients transferred to intensive care unit during the 30-day follow-up	Number of patients transferred to intensive care unit during the 30-day follow-up	30 days
Secondary	Number of days without mechanical ventilation during the 30 days following inclusion	Number of days without mechanical ventilation during the 30 days following inclusion	30 days
Secondary	adverse events attributable to antibiotic treatment during the 30 days following inclusion	adverse events attributable to antibiotic treatment during the 30 days following inclusion	30 days
Secondary	Hospital length of stay during the 30 days following inclusion	Hospital length of stay during the 30 days following inclusion	30 days