Effectiveness of the Use of Personal Protective Equipment in Addition to Tenofovir/Emtricitabine for the Prevention of the Transmission of SARS-COV-2 to Health Care Personnel. Randomized Clinical Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 950
- 主要终点
- SARS-CoV-2 infection
研究概览
简要总结
Effectiveness of the use of Tenofovir/Emtricitabine in addition to personal protective equipment for the prevention of the transmission of SARS-COV-2 to health care personnel. A Randomized Clinical Trial.
This is an experimental study whose aim is to evaluate the effectiveness of a drug to prevent infection with the virus that causes COVID-19 (SARS-CoV-2), in health care workers.
The drug under study is Tenofovir /Emtricitabine, a well-known antiretroviral, which is safe and is used as prophylaxis and treatment for HIV and other viral infections such as Hepatitis.
Several laboratory-based studies indicate that this drug has the potential to inhibit SARS-CoV-2 replication. In addition, one study in HIV infected persons found that those taking Tenofovir /Emtricitabine tended to have a lower occurrence of COVID-19.
In this study, we will compare the occurrence of infection with SARS-CoV-2/ COVID19 in health care workers between those assigned to an intervention group and those assigned to a control group. The intervention group will receive Tenofovir /Emtricitabine during 60 days in addition to the use of personal protective equipment (PPE), and the control group will receive a placebo during 60 days in addition to the use of personal protective equipment (PPE).
The study will recruit 950 health professionals above 18 and less than 70 years, working in the emergency room, COVID wards and intensive care units of seven hospitals in Colombia.
To make the comparison groups very similar, the participants will be assigned through a random mechanism to either the intervention (475), or the control (475) groups. In order to prevent biases in the evaluation of the results, neither the participants nor the clinical investigators, data managers, analysts and support personnel will know which intervention the participants are receiving.
To determine the occurrence of infection with the virus the study will use both molecular tests that detect the presence of viral genes in respiratory secretions, and serological tests that detect the response of the immune system to the virus. The study will evaluate also the safety of this drug determining the occurrence of adverse events.
详细描述
Background and Rationale The global impact of SARS-CoV-2/COVID-19 is unprecedented, and it is the greatest pandemic of a respiratory virus since the 1918 Influenza. With high infectiousness, important morbidity, and relatively high fatality in specific groups of the population, an attack rate of approximately 80%, and no vaccine available yet, the pandemic will exceed the capacity of the health care systems in many settings(1). The health care personnel represent the most valuable resource to respond to the challenges imposed by this pandemic. As health care professionals are in the frontline of response and at a high risk of infection, it is extremely important to establish effective prevention strategies that protect them from becoming infected (2). It is critical that these interventions be rigorously evaluated with designs such as RCT that provide the highest level of evidence, to make recommendations that effectively protect health care professionals and contribute to control the epidemic.
Both hand hygiene and the use of Personal Protective Equipment (PPE) are considered key strategies for the prevention of infection in health care professionals (3). However, there are few studies estimating the probability of infection with their use. Moreover, several pharmacological agents have been considered for a prophylactic use in SARS-CoV-2 infection.
As of today, there is preclinical evidence, principally in vitro, indicating antiviral effect of Tenofovir Disoproxil Fumarate / Emtiricitabine (TDF/FTC) on the SARS-CoV-2 RNA depended RNA polymerase. TDF/FTC is an approved drug for HIV treatment in combination with other antiretroviral drugs. It is widely used as HIV pre and post exposure prophylaxis, and it is the election therapy for Hepatitis B infection (4-7).
Knowing that TDF/FTC is a drug with a known security profile, has low frequency of short-term adverse events, and is capable of inhibiting SARS-CoV-2 replication in vitro, it is an interesting alternative to evaluate as prophylaxis for SARS-CoV-2 infection. Furthermore, recently, in a clinical cohort of 77590 persons living with HIV, it was documented that those receiving TDF/FTC had a risk of COVID 19 and related hospitalization between 37 a 57% lower than those who were taking other antiretroviral medications (8) Consequently, we consider relevant and justified to evaluate the use of TDF/FTC for the prevention of SARS-CoV-2 infection in a high-risk population, such as health care professionals providing clinical care to confirmed or suspected cases of COVID-19.
Tenofovir/Emtricitabine as prophylaxis for SARS-CoV-2 Infection SARS-CoV-2 is a single strand positive-sense RNA virus similar to Hepatitis C Virus, West Nile Virus, Marburg, HIV, Ebola, Dengue virus, and Rhinovirus among others. The RNA-dependent RNA polymerase (RdRp) is one of the structural proteins of SARS-CoV-2(9). The active site of RdRp is configured by two successive aspartate residues which protrude from a beta turn structure, making accessible to the surface through the nucleotide canal (10). The homology between SARS-CoV-2 RdRp and SARS-CoV-1 is higher than 97%, thus facilitating in silico studies (11).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Participant will not be informed that is either receiving or not the product of intervention, additionally, placebo will have a similar taste of the product of intervention and packaging will be the same for both.
Investigators will be masked because there is a central randomization and only the pharmacist of the study will now in which arm is assigned the participant Data analysis will be performed with an encrypted dataset which doesn't reveal which one is the intervention or which one is placebo
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Medical doctor, Nurse ,Respiratory therapist or nurse assistant who work in the emergency room, general covid ward or intensive care unit
- •Age : between 18-70 years
- •RT-PCR and serology tests for SARS-CoV-2 negative at baseline evaluation
- •Direct care of patients in the emergency room, general Covid wards or intensive care unit
- •Informed consent signed
排除标准
- •Two or more of the following : Body temperature higher than 38 Celsius, Cough of recent onset (in the previous 10 days), Dyspnea, Odinophagia, Malaise, fatigue, Acute diarrheal disease.
- •History of COVID-19 confirmed by RT-PCR or IgG antibodies
- •Family member with suspected or confirmed COVID 19
- •Cohabitating with a suspected or confirmed case of COVID-19
- •Hepatitis B anti-surface antigen antibodies lower than 10mU/ml at baseline evaluation
- •Acute or chronic Hepatitis B
- •Confirmed diagnosis of HIV infection either by clinical history or ELISA inmunassay at baseline evaluation
- •Use of TDF/FTC in the last three months for other clinical conditions
- •ALT or AST higher than 2 times the upper reference limit
- •Serum hemoglobin <11g/dl or neutropenia<1.000cell/mm3
- •Renal dysfunction defined as eGFR lower than 60ml/min (using the CKDEPI formula) or history of Chronic kidney disease Known hypersensitivity to TDF/FTC Serum phosphorus level <2.5mg/dl
- •Diagnosed osteopenia or osteoporosis
- •History of pathological fractures
- •Pregnancy, lactation or pregnancy desire during the period of the study
- •Being a participant in another Clinical trial of prevention for COVID-19
- •Use of any of the following drugs: Cidofovir, Celecoxib, Diclofenac, Ibuprofen, Metadon, Naproxen, Nimesulide, Piroxicam, Amiodarone, Quinine, Amikacin, Cephalexin, Clarithromycin, Gentamicin, Piperacillin / Tazobazorcin, Flucomycin, Flucomycin, Sulfadiazine, Vancomycin , Ganciclovir, Ledipasvir / Sofosbuvir, Sofosbuvir / Velpatasvir, Furosemide, Hydralazine, Sacubitril, Verapamil, Interferon, Hydroxyurea, Dolutegravir / Lamivudine Abacavir, Didanosine, Lamivudine, Atazanavir / cobicistat, Atazanavir / ritonavir, Darunavir / ritonavir, Darunavir / cobicistat, Indinavir, Interferon, Hydroxyurea, Cyclosporine, Mycophenolate, Sirolimus, Tacrolimus, Acetazolamide Orlistat, Probenecid, Pyridostigmine, Sevelamer, Zoledronic acid.
研究组 & 干预措施
Intervention
Tenofovir/ Emtricitabine ( 300 mg / 200 mg daily during 60 days) + Personal Protective Equipment (PPE)
干预措施: Tenofovir/ Emtricitabine ( 300 mg / 200 mg daily during 60 days) + Personal Protective Equipment (PPE) (Drug)
Placebo
(1 tablet daily during 60 days) + Personal Protective Equipment (PPE)
干预措施: Placebo (1 tablet daily during 60 days) + Personal Protective Equipment (PPE) (Other)
结局指标
主要结局
SARS-CoV-2 infection
时间窗: At any time during follow up 75 days ( 60 days of intervention + final follow-up 15 days post-intervention)
* Positivity of RT-PCR in nasopharyngeal samples in any of the measurements during follow up, or in symptomatic participants at any time. * Positive IgG antibodies against SARS- CoV-2 in any of the measurements during follow up
次要结局
- Serious and non-serious adverse events(At any time during follow up 75 days ( 60 days of intervention + final follow-up 15 days post-intervention))
- Discontinuation of using TDF/FTC for any reason(At any time during follow up 75 days ( 60 days of intervention + final follow-up 15 days post-intervention))
- Adherence to TDF/FTC(At any time during the 60 days of intervention)
- Severity of SARS-CoV-2 infection(At any time during follow up 75 days ( 60 days of intervention + final follow-up 15 days post-intervention))
研究者
Sandra Liliana Valderrama
MD, Msc
Hospital Universitario San Ignacio