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.
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.
Drug: tenofovir disoproxil and emtricitabine
Experimental drugs administration of 7-day short course TDF/FTC
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
Caen University Hospital
Caen, Calvados, France
Regional Hospital
Orléans, France
Jean-Jacques Parienti, Principal Investigator
University Hospital, Caen