Clinical Evaluation of Antiseptic Mouth Rinses to Reduce Salivary Viral Load of SARS-CoV-2 in COVID-19 Patients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Effect of 5 different mouthwashes on the SARS-Cov2 viral load.
研究概览
简要总结
As no curative treatment for SARS-CoV-2 is currently available, most public health measures to contain the pandemic are based on preventing the spread of the pathogen. The virus is transmitted by the respiratory route and by direct contact with contaminated surfaces and subsequent contact with nasal, oral or ocular mucosa. Although patients with symptomatic coronavirus disease 2019 (COVID-19) have been the main source of transmission, observations suggest that asymptomatic and incubating patients also have the ability to transmit SARS-CoV-2. Angiotensin II converting enzyme (ACE2) is the main cellular receptor for SARS-CoV-2, which interacts with the spike protein to facilitate its entry. ACE2 receptors are highly expressed in the oral cavity and present at high levels in oral epithelial cells. The mean expression of ACE2 was higher in the tongue compared to that in other oral tissues and it has been found to be higher in the minor salivary glands than in the lungs. These findings strongly suggest that the oral cavity and specifically the saliva may be a high-risk route for SARS-CoV-2 infection. Thus, strategies reducing salivary viral load could contribute to reduce the risk of transmission. Furthermore, studies using macaques as animal models have shown that SARS-CoV persists for two days in oral mucous membranes before its diffusion to the lower respiratory tract. This offers an interesting preventive and therapeutic window of opportunity for the control of this disease. For this reason, the use of mouthwashes with antiseptics that have virucidal activity can be a simple preventive strategy that could easily be applied both by infected patients before being examined by sanitary personnel and in the general population. This study is a multi-centered, blinded, parallel-group, placebo-controlled randomised clinical trial that tests the effect of four different mouthwashes (CPC, chlorhexidine, povidone-iodine and H2O2) in the salivary viral load of SARS-CoV-2 measured by qPCR at three different timepoints. A fifth group of patients using a distilled water mouth rinse is used as a control. Viral particles per ml of saliva are quantified at baseline and 30, 60 and 120 minutes after a 1-minute mouth rinse with the antiseptic or water. Our study aims to test whether any of these standard oral antiseptics appear to diminish viral load in saliva and could therefore be used as a strategy to reduce transmission risk in clinical and social settings.
详细描述
Strategies reducing salivary viral load could contribute to reduce the risk of transmission of SARS-CoV-2. Thus, the use of mouthwashes with antiseptics that have virucidal activity can be a simple and low-cost preventive strategy that could easily be applied in the general population. To evaluate the effect of several antiseptics to neutralize or reduce the SARS-CoV-2 viral load in vivo in saliva samples, a multicentre, randomized, blind, five-parallel-group, placebo-controlled trial has been designed.
The study will be performed in Madrid, Valencia and Murcia regions in Spain, in five different hospitals: Fundación Jiménez Díaz University Hospital (Madrid, Spain), Villalba University General Hospital (Madrid, Spain), Infanta Elena University Hospital (Madrid, Spain), Virgen de la Arixaca University Hospital (Murcia, Spain) and Clínico de Valencia University Hospital (Valencia, Spain).
Every patient included is previously diagnosed and hospitalized because of SARS-COV-2 infection, being admitted mainly for respiratory pathology. All of them will be adults (age >18 years) and provide their voluntary written or oral consent to participation according to the hospital's ethics committee recommendations.
After approval of consent, the hospital staff responsible for the interventions will consecutively assign each participant a code following the order from a previously randomly generated table. The code will consist of a patient number and a letter corresponding to one of the five study groups (A, B, C, D and E), that will be known to the clinical personnel but unknown to the laboratory personnel who will process samples and extract RNA, as well as to those that will analyse the data. In this way, participants will be randomly assigned to one of the five treatment groups and the blind will be achieved by using identical tubes with the same volume for both mouthwashes and placebo.
Every included patient is asked not to eat, drink anything but water, chew gum, smoke, brush their teeth, or use any mouthwash for one hour prior to sample collection. In addition, they are not allowed to drink for half an hour after the mouthwash and eat for the entire test.
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, Investigator, Outcomes Assessor)
盲法说明
The hospital staff consecutively assigned each participant a code following the order from a previously randomly generated table.
The code were unknown to the personnel who processed the samples and to those that analyzed the data.
Participants were blinded by using identical tubes with the same volume for both mouthwashes and placebo.
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
- •Lower than 7 days from the positive SARS-COV-2 PCR test of a nasopharyngeal sample
- •Have the ability to donate saliva samples and perform mouthwash
排除标准
- •Patient participation in a COVID-19 research study using experimental drugs,
- •Use of an antiseptic mouthwash for 48 h before the start of the study
- •Any known hypersensitivity or allergy to components of the mouthwashes.
研究组 & 干预措施
Cetylpyridinium chloride 0,07% (Vitis Xtra Forte©)
Cetylpyridinium chloride 0,07% (Vitis Xtra Forte©) contains cetylpyridinium chloride (C21H38ClN).
Rinses were ready to use in their commercial formulas.
干预措施: Vitis Xtra Forte© (Drug)
Control (Distilled Water)
Distilled water.
干预措施: Distilled Water (Drug)
Povidone-iodine 2% (Betadine© bucal 100 mg/ml)
Povidone-iodine 2% (Betadine© bucal 100 mg/ml) (Mylan Pharmaceuticals, S.L., Spain).
The concentration was adjusted to those previously indicated by diluting commercial formulas with distilled water minutes before rinsing (3 mL of povidone-iodine 10% for oral use - Betadine© with 12 mL of distilled water).
干预措施: Betadine© bucal 100 mg/ml (Drug)
Hydrogen peroxide 1% (Oximen® 3%)
Hydrogen peroxide 1% (Oximen® 3%) (Reig Jofré, S.A., Spain). The concentration was adjusted to those previously indicated by diluting commercial formulas with distilled water minutes before rinsing (5 mL of hydrogen peroxide 3% - Oximen© with 10 mL of distilled water).
干预措施: Oximen® 3% (Drug)
Clorhexidine 0,12% (Clorhexidine Dental PHB©)
Clorhexidine 0,12% (Clorhexidine Dental PHB©) contains clorhexidine (C22H30N10Cl2).
Rinses were ready to use in their commercial formulas.
干预措施: Clorhexidine Dental PHB© (Drug)
结局指标
主要结局
Effect of 5 different mouthwashes on the SARS-Cov2 viral load.
时间窗: Minute 0 (before mouthwash) - Minute 30 (after mouthwash) - Minute 60 (after mouthwash) - Minute 120 (after mouthwash)
Determine the changes on the SARS-Cov2 viral load in saliva tested in vivo, between baseline values and those obtained at 30 minutes, at 60 minutes and at 120 minutes, after the use of 5 different mouthwashes randomized on 98 COVID-19 patients.
Effect of 5 different mouthwashes on the infective SARS-Cov2 viral load in saliva.
时间窗: Minute 0 (before mouthwash) - Minute 30 (after mouthwash) - Minute 60 (after mouthwash)
Determine the changes on the SARS-Cov2 infective viral load in saliva tested in vivo, between baseline values and those obtained at 30 minutes and at 60 minutes after the use of 5 different mouthwashes randomized on 62 COVID-19 patients.
次要结局
未报告次要终点
研究者
Alejandro Mira Obrador
BSc in Biological Sciences (Alicante University), MSc PhD (Oxford University), Senior Researcher (FISABIO Foundation)
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
