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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Phase 3: Rate of non-contagious nasopharyngeal sample for SARS-CoV2 by PCR on Day-4 with Ct > or = 28
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Biologists in Endpoint Adjudication committee
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Diagnosis of pregnancy during treatment
研究组 & 干预措施
TDF / FTC
2 tablets on Day-1 then 1 tablet/day for 6 days
干预措施: tenofovir disoproxil and emtricitabine (Drug)
结局指标
主要结局
Phase 3: Rate of non-contagious nasopharyngeal sample for SARS-CoV2 by PCR on Day-4 with Ct > or = 28
时间窗: Day-4 after the start of study
Nasopharyngeal swab performed at day-4 with RT-PCR for SARS-CoV2
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)
时间窗: Day-4 after the start of study
Nasopharyngeal swab performed at baseline and day-4 with RT-PCR for SARS-CoV2
次要结局
- Phase 3: Symptoms score(From the start of the study to Day-7)
- 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)
- Phase 2B/3: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](From the start of the study to Day-7)
- Phase 3: Proportion of secondary hospitalization(Day-15)