Effect of Tenofovir/Emtricitabine in Patients Recently Infected With SARS-COV2 (Covid-19) Discharged Home (AR0-CORONA)
Primary Purpose
Covid19
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
tenofovir disoproxil and emtricitabine
Sponsored by
About this trial
This is an interventional treatment trial for Covid19 focused on measuring COVID-19, TDF/FTC, ambulatory patients, Replication rate of the virus
Eligibility Criteria
Inclusion Criteria:
- Patients 18 years and over
- SARS-CoV2 Infection confirmed by PCR
- Patients who do not require immediate hospitalization
- Signed informed consent
Non-Inclusion criteria:
- Patients with HIV or Hepatitis B
- Symptoms suggestive of a SARS-CoV2 infection that has been progressing for more than 7 days
- Asympomatic patients with unknown date of infection or date of infection>7 days
- Chronic HCV infection
- Contraindication to the use of TDF/FTC
- Hypersensitivity to tenofovir, to emtricitabine or to any of the excipients (especially lactose)
- Glomerular filtration rate <80mL / min
- Recent (less than 7 days) or concomitant use of NSAIDs or other nephrotoxic drugs (antiinfectives, immunosuppressants, allopurinol, lithium
- need for hospitalization for contemporary decompensation of a comorbidity
- need for hospitalization due to SARS-CoV2 infection:
- Capillary oximetry less than 95%
- clinical evaluation by the investigating doctor leading to hospitalization
- Pregnant or breastfeeding women
Exclusion Criteria:
- Diagnosis of pregnancy during treatment
Sites / Locations
- Caen University Hospital
- Regional Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
TDF / FTC
usual care
Arm Description
2 tablets on Day-1 then 1 tablet/day for 6 days
Standard of Care
Outcomes
Primary Outcome Measures
Phase 2B: Reduction of SARS-CoV2 viral load assessed by Ct PCR at day-4 adjusted on Ct PCR SARS-CoV2 viral load at baseline (ANCOVA)
Nasopharyngeal swab performed at baseline and day-4 with RT-PCR for SARS-CoV2
Phase 3: Rate of non-contagious nasopharyngeal sample for SARS-CoV2 by PCR on Day-4 with Ct > or = 28
Nasopharyngeal swab performed at day-4 with RT-PCR for SARS-CoV2
Secondary Outcome Measures
Phase 2B/3: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Number of adverse events according to the CTCAE grade
Phase 3: Symptoms score
Self-reported COVID-19 related symptoms
Phase 3: Proportion of secondary hospitalization
Assessed by investigators up to day-15
Phase 3: Rate of non-contagious nasopharyngeal sample for SARS-CoV2 by PCR on Day-7 with Ct > or = 28
Nasopharyngeal swab performed at day-7 with RT-PCR for SARS-CoV2
Full Information
NCT ID
NCT04685512
First Posted
November 16, 2020
Last Updated
June 29, 2021
Sponsor
University Hospital, Caen
1. Study Identification
Unique Protocol Identification Number
NCT04685512
Brief Title
Effect of Tenofovir/Emtricitabine in Patients Recently Infected With SARS-COV2 (Covid-19) Discharged Home
Acronym
AR0-CORONA
Official Title
Effect of Tenofovir/Emtricitabine Short Course on Viral Clearance in Patients Recently Infected With SARS-COV2 (Covid-19) Not Requiring Hospitalization: a Phase IIB/III Multicenter Open-label Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
November 18, 2020 (Actual)
Primary Completion Date
April 1, 2021 (Actual)
Study Completion Date
May 1, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Caen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
COVID-19 pandemic is currently affecting the globe. To date, there is no effective oral therapy against SARS-CoV2 infection. The investigators propose to test as a repurposing drug combination, a short course of tenofovir disoproxil and emtricitabine (TDF/FTC), as a proof-of-concept randomized open-label study to test its viral efficacy against SARS-CoV2.
Detailed Description
The SARS-CoV2 pandemic is causing morbidity and mortality. There is no cure. Remdesivir is a nucleotide analogue that has demonstrated its efficacy in vitro against SARS-CoV2 and in humans (shorten symptoms duration by 2 days without improving survival), but it is used parenterally. TDF belongs to the same therapeutic class, represents a promising avenue of research. TDF/FTC demonstrated in vivo efficacy against SARS-CoV2 in preclinical animal models and its use is associated with reduced risk of SARS-CoV2 infection in 2 large cohorts of HIV infected patients.The objective of this work is to evaluate the anti-viral efficacy of the TDF/FTC combination in short course in patients infected with SARS-CoV2 on an outpatient basis.
The investigators propose a multicenter, open-label, phase 2B/3 randomized trial of a 7-day treatment with TDF / FTC (2 tablets on Day-1 then 1 tablet / day for 6 days) according to the dosage used in pre-exposure prophylaxis for HIV. This study should include 60 outpatients (Phase 2B) and 120 additional outpatients (Phase III) who were diagnosed with SARS-CoV2 positive and with no contraindication to TDF / FTC and without criteria for hospitalization. The primary endpoint of the phase 2B will be the SARS-CoV2 antiviral efficacy quantified by RT-PCR nasopharyngeal sample Ct increase on Day-4 compared to baseline. The primary endpoint of the phase 3 will be the rate of non-contagious PCR on Day-4 from a nasopharyngeal sample. Secondary endpoints will be tolerance, symptoms resolution, percentage of hospitalization and the rate of non-contagious PCR on Day-7 from a nasopharyngeal sample.
The investigators hypothesize that compared to no treatment, treatment with TDF/FTC reduces at Day-4:
SARS-CoV2 viral load corresponding to a 4-point +/-5 increase in Ct (Phase 2B)
contagious carriage from 80% to 60% (Phase 3).
The AR0-CORONA investigators hope, through this study, to be able to validate an anti-viral treatment making it possible to reduce the duration of contagiousness and thus contribute to attenuating the R0 of recently infected patients carrying SARS-CoV2 who are isolated at home.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19
Keywords
COVID-19, TDF/FTC, ambulatory patients, Replication rate of the virus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Phase 2B: 30 treated, 30 untreated - 1 interim analysis planned after inclusion of 30 patients / Phase 3: 90 treated, 90 untreated - 2 interim analyses planned after inclusion of 60 and 120 patients
Masking
Outcomes Assessor
Masking Description
Biologists in Endpoint Adjudication committee
Allocation
Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TDF / FTC
Arm Type
Experimental
Arm Description
2 tablets on Day-1 then 1 tablet/day for 6 days
Arm Title
usual care
Arm Type
No Intervention
Arm Description
Standard of Care
Intervention Type
Drug
Intervention Name(s)
tenofovir disoproxil and emtricitabine
Intervention Description
Experimental drugs administration of 7-day short course TDF/FTC
Primary Outcome Measure Information:
Title
Phase 2B: Reduction of SARS-CoV2 viral load assessed by Ct PCR at day-4 adjusted on Ct PCR SARS-CoV2 viral load at baseline (ANCOVA)
Description
Nasopharyngeal swab performed at baseline and day-4 with RT-PCR for SARS-CoV2
Time Frame
Day-4 after the start of study
Title
Phase 3: Rate of non-contagious nasopharyngeal sample for SARS-CoV2 by PCR on Day-4 with Ct > or = 28
Description
Nasopharyngeal swab performed at day-4 with RT-PCR for SARS-CoV2
Time Frame
Day-4 after the start of study
Secondary Outcome Measure Information:
Title
Phase 2B/3: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Description
Number of adverse events according to the CTCAE grade
Time Frame
From the start of the study to Day-7
Title
Phase 3: Symptoms score
Description
Self-reported COVID-19 related symptoms
Time Frame
From the start of the study to Day-7
Title
Phase 3: Proportion of secondary hospitalization
Description
Assessed by investigators up to day-15
Time Frame
Day-15
Title
Phase 3: Rate of non-contagious nasopharyngeal sample for SARS-CoV2 by PCR on Day-7 with Ct > or = 28
Description
Nasopharyngeal swab performed at day-7 with RT-PCR for SARS-CoV2
Time Frame
Day-7 after the start of study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients 18 years and over
SARS-CoV2 Infection confirmed by PCR
Patients who do not require immediate hospitalization
Signed informed consent
Non-Inclusion criteria:
Patients with HIV or Hepatitis B
Symptoms suggestive of a SARS-CoV2 infection that has been progressing for more than 7 days
Asympomatic patients with unknown date of infection or date of infection>7 days
Chronic HCV infection
Contraindication to the use of TDF/FTC
Hypersensitivity to tenofovir, to emtricitabine or to any of the excipients (especially lactose)
Glomerular filtration rate <80mL / min
Recent (less than 7 days) or concomitant use of NSAIDs or other nephrotoxic drugs (antiinfectives, immunosuppressants, allopurinol, lithium
need for hospitalization for contemporary decompensation of a comorbidity
need for hospitalization due to SARS-CoV2 infection:
Capillary oximetry less than 95%
clinical evaluation by the investigating doctor leading to hospitalization
Pregnant or breastfeeding women
Exclusion Criteria:
- Diagnosis of pregnancy during treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Jacques Parienti
Organizational Affiliation
University Hospital, Caen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Caen University Hospital
City
Caen
State/Province
Calvados
ZIP/Postal Code
14000
Country
France
Facility Name
Regional Hospital
City
Orléans
ZIP/Postal Code
45100
Country
France
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
We encourage contact the corresponding author for academic IPD sharing
Citations:
Citation
Parienti JJ et al. EClinicalMedicine 2021: https://authors.elsevier.com/sd/article/S2589-5370(21)00273-X
Results Reference
result
PubMed Identifier
34222849
Citation
Parienti JJ, Prazuck T, Peyro-Saint-Paul L, Fournier A, Valentin C, Brucato S, Verdon R, Seve A, Colin M, Lesne F, Guinard J, Ar Gouilh M, Dina J, Vabret A, Hocqueloux L. Effect of Tenofovir Disoproxil Fumarate and Emtricitabine on nasopharyngeal SARS-CoV-2 viral load burden amongst outpatients with COVID-19: A pilot, randomized, open-label phase 2 trial. EClinicalMedicine. 2021 Aug;38:100993. doi: 10.1016/j.eclinm.2021.100993. Epub 2021 Jun 27.
Results Reference
derived
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Effect of Tenofovir/Emtricitabine in Patients Recently Infected With SARS-COV2 (Covid-19) Discharged Home
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