Covid19
Conditions
Keywords
COVID-19, TDF/FTC, ambulatory patients, Replication rate of the virus
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.
Interventions
Experimental drugs administration of 7-day short course TDF/FTC
Sponsors
University Hospital, Caen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Biologists in Endpoint Adjudication committee
Intervention 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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Day-4 after the start of study | 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 | Day-4 after the start of study | Nasopharyngeal swab performed at day-4 with RT-PCR for SARS-CoV2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2B/3: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | From the start of the study to Day-7 | Number of adverse events according to the CTCAE grade |
| Phase 3: Symptoms score | From the start of the study to Day-7 | Self-reported COVID-19 related symptoms |
| Phase 3: Proportion of secondary hospitalization | Day-15 | 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 | Day-7 after the start of study | Nasopharyngeal swab performed at day-7 with RT-PCR for SARS-CoV2 |
Countries
France
Outcome results
None listed