Azithromycin+Amoxicillin/Clavulanate vs Amoxicillin/Clavulanate in COVID19 Patients With Pneumonia in Non-intensive Unit (AziA)
Primary Purpose
COVID-19 Pneumonia
Status
Unknown status
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Azithromycin with amoxicillin/clavulanate
amoxicillin/clavulanate
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 Pneumonia
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)
Sites / Locations
- Chu Angers
- CHD Vendée
- CHU Poitiers
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Azithromycin with amoxicillin/clavulanate
Amoxicillin/clavulanate
Arm Description
Combination of azithromycin during 4 days with amoxicillin/clavulanate during 7 days.
Amoxicillin/clavulanate every day during 7 days.
Outcomes
Primary Outcome Measures
Rate of positive SARS-CoV-2 RT-PCR
Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal sample
Secondary Outcome Measures
Rate of positive SARS-CoV-2 RT-PCR
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-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)
Total duration of antibiotic treatment during the 30 days following inclusion
Total duration of antibiotic treatment during the 30 days following inclusion
Number of all-cause mortality during the 30 days following inclusion
Number of all-cause mortality during the 30 days following inclusion
Number of in-hospital mortality during the 30 days following inclusion
Number of in-hospital mortality during the 30 days following inclusion
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
Number of days without mechanical ventilation during the 30 days following inclusion
Number of days without mechanical ventilation during the 30 days following inclusion
adverse events attributable to antibiotic treatment during the 30 days following inclusion
adverse events attributable to antibiotic treatment during the 30 days following inclusion
Hospital length of stay during the 30 days following inclusion
Hospital length of stay during the 30 days following inclusion
Full Information
NCT ID
NCT04363060
First Posted
April 23, 2020
Last Updated
April 27, 2020
Sponsor
Nantes University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04363060
Brief Title
Azithromycin+Amoxicillin/Clavulanate vs Amoxicillin/Clavulanate in COVID19 Patients With Pneumonia in Non-intensive Unit
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Unknown status
Study Start Date
April 30, 2020 (Anticipated)
Primary Completion Date
July 30, 2020 (Anticipated)
Study Completion Date
July 30, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nantes University Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19 Pneumonia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
104 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Azithromycin with amoxicillin/clavulanate
Arm Type
Experimental
Arm Description
Combination of azithromycin during 4 days with amoxicillin/clavulanate during 7 days.
Arm Title
Amoxicillin/clavulanate
Arm Type
Active Comparator
Arm Description
Amoxicillin/clavulanate every day during 7 days.
Intervention Type
Combination Product
Intervention Name(s)
Azithromycin with amoxicillin/clavulanate
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
amoxicillin/clavulanate
Intervention Description
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
Primary Outcome Measure Information:
Title
Rate of positive SARS-CoV-2 RT-PCR
Description
Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal sample
Time Frame
Day 6
Secondary Outcome Measure Information:
Title
Rate of positive SARS-CoV-2 RT-PCR
Description
Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal sample
Time Frame
Day 10
Title
Clinical evolution on the World Health Organization Ordinal Scale for Clinical Improvement for COVID-19
Description
Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 score. Scale ranging from 0 to 8 (0:unifected; 8:dead)
Time Frame
day 6, day 10, and day 30
Title
Total duration of antibiotic treatment during the 30 days following inclusion
Description
Total duration of antibiotic treatment during the 30 days following inclusion
Time Frame
30 days
Title
Number of all-cause mortality during the 30 days following inclusion
Description
Number of all-cause mortality during the 30 days following inclusion
Time Frame
30 days
Title
Number of in-hospital mortality during the 30 days following inclusion
Description
Number of in-hospital mortality during the 30 days following inclusion
Time Frame
30 days
Title
Number of patients transferred to intensive care unit during the 30-day follow-up
Description
Number of patients transferred to intensive care unit during the 30-day follow-up
Time Frame
30 days
Title
Number of days without mechanical ventilation during the 30 days following inclusion
Description
Number of days without mechanical ventilation during the 30 days following inclusion
Time Frame
30 days
Title
adverse events attributable to antibiotic treatment during the 30 days following inclusion
Description
adverse events attributable to antibiotic treatment during the 30 days following inclusion
Time Frame
30 days
Title
Hospital length of stay during the 30 days following inclusion
Description
Hospital length of stay during the 30 days following inclusion
Time Frame
30 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Emmanuel MONTASSIER
Phone
+33 (0)2 53 48 20 38
Email
Emmanuel.montassier@chu-nantes.fr
Facility Information:
Facility Name
Chu Angers
City
Angers
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vincent DUBEE, MD, PhD
Facility Name
CHD Vendée
City
La Roche-sur-Yon
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Romain DECOURS, MD, PhD
Facility Name
CHU Poitiers
City
Poitiers
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Blandine RAMMAERT, MD, PhD
12. IPD Sharing Statement
Learn more about this trial
Azithromycin+Amoxicillin/Clavulanate vs Amoxicillin/Clavulanate in COVID19 Patients With Pneumonia in Non-intensive Unit
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