scholarly journals A quadruple blind, randomised controlled trial of gargling agents in reducing intraoral viral load among hospitalised COVID-19 patients: A structured summary of a study protocol for a randomised controlled trial

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Farhan Raza Khan ◽  
Syed Murtaza Raza Kazmi ◽  
Najeeha Talat Iqbal ◽  
Junaid Iqbal ◽  
Syed Tariq Ali ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Hydrogen Peroxide ◽  
Viral Load ◽  
Hypertonic Saline ◽  
Povidone Iodine ◽  
Nasal Lavage ◽  
Study Group ◽  
Neem Extract ◽  
Full Protocol ◽  
Randomised Controlled

Abstract Objectives 1- To compare the effectiveness of 1% Hydrogen peroxide, 0.2% Povidone-Iodine, 2% hypertonic saline and a novel solution Neem extract (Azardirachta indica) in reducing intra-oral viral load in COVID-19 positive patients. 2- To determine the salivary cytokine profiles of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL- 17 among COVID-19 patients subjected to 1% Hydrogen peroxide, 0.2% Povidone-Iodine, 2% hypertonic saline or Neem extract (Azardirachta indica) based gargles. Trial design This will be a parallel group, quadruple blind-randomised controlled pilot trial with an add on laboratory based study. Participants A non-probability, purposive sampling technique will be followed to identify participants for this study. The clinical trial will be carried out at the Aga Khan University Hospital (AKUH), Karachi, Pakistan. The viral PCR tests will be done at main AKUH clinical laboratories whereas the immunological tests (cytokine analysis) will be done at the Juma research laboratory of AKUH. The inclusion criteria are laboratory-confirmed COVID-19 positive patients, male or female, in the age range of 18-65 years, with mild to moderate disease, already admitted to the AKUH. Subjects with low Glasgow coma score, with a history of radiotherapy or chemotherapy, who are more than 7 days past the onset of COVID- 19 symptoms, or intubated or edentulous patients will be excluded. Patients who are being treated with any form of oral or parenteral antiviral therapy will be excluded, as well as patients with known pre-existing chronic mucosal lesions such as lichen planus. Intervention and comparator Group A (n=10) patients on 10 ml gargle and nasal lavage using 0.2% Povidone-Iodine (Betadiene® by Aviro Health Inc./ Pyodine® by Brooks Pharma Inc.) for 20-30 seconds, thrice daily for 6 days. Group B (n=10) patients will be subjected to 10 ml gargle and nasal lavage using 1% Hydrogen peroxide (HP® by Karachi Chemicals Products Inc./ ActiveOxy® by Boumatic Inc.) for 20-30 seconds, thrice daily for 6 days. Group C will comprised of (n=10) subjects on 10ml gargle and nasal lavage using Neem extract solution (Azardirachta indica) formulated by Karachi University (chemistry department laboratories) for 20-30 seconds, thrice daily for 6 days. Group D (n=10) patients will use 2% hypertonic saline (Plabottle® by Otsuka Inc.) gargle and nasal lavage for a similar time period. Group E (n=10) will serve as positive controls. These will be given simple distilled water gargles and nasal lavage for 20-30 seconds, thrice daily for six days. For nasal lavage, a special douche syringe will be provided to each participant. Its use will be thoroughly explained by the data collection officer. After each use, the patient is asked not to eat, drink, or rinse their mouth for the next 30 minutes. Main outcomes The primary outcome is the reduction in the intra-oral viral load confirmed with real time quantitative PCR. Randomisation The assignment to the study group/ allocation will be done using the sealed envelope method under the supervision of Clinical Trial Unit (CTU) of Aga Khan University, Karachi, Pakistan. The patients will be randomised to their respective study group (1:1:1:1:1 allocation ratio) immediately after the eligibility assessment and consent administration is done. Blinding (masking) The study will be quadruple-blinded. Patients, intervention provider, outcome assessor and the data collection officer will be blinded. The groups will be labelled as A, B, C, D or E. The codes of the intervention will be kept in lock & key at the CTU and will only be revealed at the end of study or if the study is terminated prematurely. Numbers to be randomised (sample size) As there is no prior work on this research question, so no assumptions for the sample size calculation could be made. The present study will serve as a pilot trial. We intend to study 50 patients in five study groups with 10 patients in each study group. For details, please refer to Fig. 1 for details. Trial Status Protocol version is 7.0, approved by the department and institutional ethics committees and clinical trial unit of the university hospital. Recruitment is planned to start as soon as the funding is sanctioned. The total duration of the study is expected to be 6 months i.e. August 2020-January 2021. Trial registration This study protocol was registered at www.clinicaltrials.gov on 10 April 2020 NCT04341688. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

scholarly journals Multicentre, open-label, randomised, controlled clinical trial comparing 2% chlorhexidine–70% isopropanol and 5% povidone iodine–69% ethanol for skin antisepsis in reducing surgical-site infection after cardiac surgery: the CLEAN 2 study protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. e026929
Author(s):  
Matthieu Boisson ◽  
Pierre Corbi ◽  
Thomas Kerforne ◽  
Lionel Camilleri ◽  
Mathieu Debauchez ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cardiac Surgery ◽  
Povidone Iodine ◽  
Controlled Clinical Trial ◽  
Site Infection ◽  
Open Label ◽  
Initial Surgery ◽  
Randomised Controlled Clinical Trial ◽  
Skin Antisepsis ◽  
Randomised Controlled

Introduction Surgical-site infection (SSI) is the second most frequent cause of healthcare-associated infection worldwide and is associated with increased morbidity, mortality and healthcare costs. Cardiac surgery is clean surgery with low incidence of SSI, ranging from 2% to 5%, but with potentially severe consequences. Perioperative skin antisepsis with an alcohol-based antiseptic solution is recommended to prevent SSI, but the superiority of chlorhexidine (CHG)–alcohol over povidone iodine (PVI)–alcohol, the two most common alcohol-based antiseptic solutions used worldwide, is controversial. We aim to evaluate whether 2% CHG–70% isopropanol is more effective than 5% PVI–69% ethanol in reducing the incidence of reoperation after cardiac surgery. Methods and analysis The CLEAN 2 study is a multicentre, open-label, randomised, controlled clinical trial of 4100 patients undergoing cardiac surgery. Patients will be randomised in 1:1 ratio to receive either 2% CHG–70% isopropanol or 5% PVI–69% ethanol for perioperative skin preparation. The primary endpoint is the proportion of patients undergoing any re-sternotomy between day 0 and day 90 after initial surgery and/or any reoperation on saphenous vein/radial artery surgical site between day 0 and day 30 after initial surgery. Data will be analysed on the intention-to-treat principle. Ethics and dissemination This protocol has been approved by an independent ethics committee and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. Trial registration number EudraCT 2017-005169-33 and NCT03560193.

scholarly journals Salivary and Nasal Detection of the SARS-CoV-2 Virus After Antiviral Mouthrinses (BBCovid): A structured summary of a study protocol for a randomised controlled trial

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Florence Carrouel ◽  
Stéphane Viennot ◽  
Martine Valette ◽  
Jean-Marie Cohen ◽  
Claude Dussart ◽  
...  
Keyword(s):  
Viral Load ◽  
Randomised Controlled Trial ◽  
Real Time ◽  
Outcome Measures ◽  
Real Time Pcr ◽  
Controlled Trial ◽  
Full Protocol ◽  
Pcr Assays ◽  
Randomised Controlled ◽  
Hospital Center

Abstract Objectives - To describe the evolution of the SARS-CoV-2 salivary viral load of patients infected with Covid-19, performing 7 days of tri-daily mouthwashes with and without antivirals. - To compare the evolution of the SARS-CoV-2 nasal and salivary viral load according to the presence or absence of antivirals in the mouthwash. Trial design This is a multi-center, randomised controlled trial (RCT) with two parallel arms (1:1 ratio). Participants Inclusion criteria - Age: 18-85 years old - Clinical diagnosis of Covid-19 infection - Clinical signs have been present for less than 8 days - Virological confirmation - Understanding and acceptance of the trial - Written agreement to participate in the trial Exclusion criteria - Pregnancy, breastfeeding, inability to comply with protocol, lack of written agreement - Patients using mouthwash on a regular basis (more than once a week) - Patient at risk of infectious endocarditis - Patients unable to answer questions - Uncooperative patient The clinical trial is being conducted with the collaboration of three French hospital centers: Hospital Center Emile Roux (Le Puy en Velay, France), Clinic of the Protestant Infirmary (Lyon, France) and Intercommunal Hospital Center (Mont de Marsan, France). Intervention and comparator Eligible participants will be allocated to one of the two study groups. Intervention group: patients perform a tri-daily mouthwash with mouthwash containing antivirals (β-cyclodextrin and Citrox®) for a period of 7 days. Control group: patients perform a tri-daily mouthwash with a placebo mouthwash for a period of 7 days. Main outcomes Primary Outcome Measures: Change from Baseline amount of SARS-CoV-2 in salivary samples at 4 and 9 hours, 1, 2, 3, 4, 5 and 6 days. Real-time PCR assays are performed to assess salivary SARS-CoV 2 viral load. Secondary Outcome Measures: Change from Baseline amount of SARS-CoV-2 virus in nasal samples at 6 days. Real-time PCR assays are performed to assess nasal SARS-CoV-2 viral load. Randomisation Participants meeting all eligibility requirements are allocated to one of the two study arms (mouthwash with β-cyclodextrin and Citrox® or mouthwash without β-cyclodextrin and Citrox®) in a 1:1 ratio using simple randomisation with computer generated random numbers. Blinding (masking) Participants, doctors and nurses caring for participants, laboratory technicians and investigators assessing the outcomes will be blinded to group assignment. Numbers to be randomised (sample size) Both the intervention and control groups will be composed of 103 participants, so the study will include a total of 206 participants. Trial Status The current protocol version is 6, August 4th, 2020. Recruitment began on April 6, 2020 and is anticipated to be complete by April 5, 2021. As of October 2, 2020, forty-two participants have been included. Trial registration This trial was registered on 20 April 2020 at www.clinicaltrials.gov with the number NCT04352959. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.” The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).”

scholarly journals Review of the use of nasal and oral antiseptics during a global pandemic

2021 ◽  
Vol 16 (2) ◽  
pp. 119-130
Author(s):  
Christopher Stathis ◽  
Nikolas Victoria ◽  
Kristin Loomis ◽  
Shaun A Nguyen ◽  
Maren Eggers ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Viral Load ◽  
Viral Replication ◽  
Hypertonic Saline ◽  
Hypochlorous Acid ◽  
Povidone Iodine ◽  
Nasal Sprays ◽  
Early Stages ◽  
Global Pandemic

A review of nasal sprays and gargles with antiviral properties suggests that a number of commonly used antiseptics including povidone-iodine, Listerine®, iota-carrageenan and chlorhexidine should be studied in clinical trials to mitigate both the progression and transmission of SARS-CoV-2. Several of these antiseptics have demonstrated the ability to cut the viral load of SARS-CoV-2 by 3–4 log10 in 15–30 s  in vitro. In addition, hypertonic saline targets viral replication by increasing hypochlorous acid inside the cell. A number of clinical trials are in process to study these interventions both for prevention of transmission, prophylaxis after exposure, and to diminish progression by reduction of viral load in the early stages of infection.

scholarly journals Comparison of olanexidine versus povidone-iodine for preventing surgical site infection in gastrointestinal surgery: study protocol for a multicentre, single-blind, randomised controlled clinical trial

BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e028269 ◽  
Author(s):  
Masashi Takeuchi ◽  
Hideaki Obara ◽  
Hirofumi Kawakubo ◽  
Masahiro Shinoda ◽  
Koji Okabayashi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Surgical Site Infection ◽  
Povidone Iodine ◽  
Gastrointestinal Surgery ◽  
Institutional Review Board ◽  
Controlled Clinical Trial ◽  
Site Infection ◽  
Institutional Review ◽  
Randomised Controlled Clinical Trial ◽  
Randomised Controlled

IntroductionThe prevalence of surgical site infection (SSI) remains higher in gastrointestinal surgery than in other surgeries. Although several guidelines have indicated the efficacy of chlorhexidine and povidone-iodine in reducing the SSI rate, the optimal recommendation has still not been established. Therefore, it is necessary to determine the more effective antiseptic for surgical site preparation. Olanexidine (1.5% olanedine, Otsuka Pharmaceutical Factory, Tokushima, Japan), which is a new antiseptic in Japan, has antimicrobial activity against a wide range of bacteria, including Gram-positive and Gram-negative bacteria. Our study will contribute to determining a new antiseptic for use in gastrointestinal and other surgeries.Methods and analysisWe propose a multicentre, randomised controlled clinical trial for comparing two treatments, that is, 1.5% olanexidine or 10% povidone-iodine, for surgical skin preparation to prevent SSI in clean-contaminated gastrointestinal surgeries with surgical wounds. Patients aged ≥20 years at the time of consent will be included. The primary outcome measure is the 30-day postoperative SSI rate. For the primary analysis, which is aimed at comparing the treatment effects, the adjusted risk ratio and its 95% CI will be estimated using the Mantel-Haenszel method.Ethics and disseminationThe protocol was first approved by the Institutional Review Board of Keio University School of Medicine, followed by the institutional review board of each participating site. Participant recruitment began in June 2018. The final results will be published in international peer-reviewed medical journals.Trial registration numberUMIN 000031560; Pre-results.

scholarly journals Virucidal effect of povidone iodine on COVID-19 in the nasopharynx: A structured summary of a study protocol for an open-label randomized clinical trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mohammad Jahid Hasan ◽  
S. K. Nurul Fattah Rumi ◽  
Sultana Sahana Banu ◽  
A. K. M. Nasir Uddin ◽  
Md Shahnoor Islam ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Renal Failure ◽  
Povidone Iodine ◽  
Intervention Group ◽  
Distilled Water ◽  
Trial Protocol ◽  
Open Label ◽  
Nasal Irrigation ◽  
Comparator Group ◽  
Full Protocol

Abstract Objective General: To assess the virucidal efficacy of povidone iodine (PVP-I) on COVID-19 virus located in the nasopharynx Specific: i. To evaluate the efficacy of povidone iodine (PVP-I) to removeCOVID-19 virus located in the nasopharynx ii. To assess the adverse events of PVP-I Trial design This is a single-center, open-label randomized clinical trial with a 7-arm parallel-group design. Participants The study will be conducted at Dhaka Medical College Hospital, Dhaka, Bangladesh. Inclusion criteria All RT-PCR-confirmed COVID-19 cases aged between 15-90 years with symptoms for the past 4 days will be screened. Those who give informed consent, are willing to participate, and accept being randomized to any assigned group will also be considered for final inclusion. Exclusion criteria Patients with known sensitivity to PVP-I aqueous antiseptic solution or any of its listed excipients or previously diagnosed thyroid disease or who had a history of chronic renal failure: stage ≥3 by estimated glomerular filtration rate (eGFR) Modification of Diet in Renal Disease (MDRD) or had acute renal failure (KDIGO ≥stage 2: creatinine ≥2 times from the baseline) or patients who required invasive or noninvasive ventilation or planned within the next 6 hours were considered for exclusion. Moreover, lactating or pregnant women will also be restricted to include here. Intervention and comparator This RCT consist of seven arms: Arm-1 (intervention group): will receive povidone iodine (PVP-I) nasal irrigation (NI) at a concentration of 0.4% Arm-2 (intervention group): will receive PVP-I nasal irrigation at a concentration of 0.5% Arm-3 (intervention group): will receive PVP-I nasal irrigation at a concentration of 0.6%. Arm-4 (intervention group): will receive PVP-I nasal spray (NS) at a concentration of 0.5%. Arm-5 (intervention group): will receive PVP-I nasal spray at a concentration of 0.6%. Arm-6 (placebo comparator group): will receive distilled water through NI Arm-7 (Placebo comparator group): will receive distilled water through NS The intervention arms will be compared to the placebo comparator arms. Other supportive and routine care will be the same in both groups. Main outcomes The primary outcome is the proportion of cases that remain COVID-19 positive following the intervention. It will be assessed from 1 minutes to 15 minutes after the intervention. Any occurrence of adverse effects following the intervention will be documented as a secondary outcome. Randomization The assignment to the study (intervention) or control (comparator) group will be allocated in equal numbers through randomization using random number generation in Microsoft Excel by a statistician who is not involved in the trial. The allocation scheme will be made by an independent statistician using a sealed envelope. The participants will be allocated immediately after the eligibility assessment and consenting procedures. Blinding (masking) This is an open-label clinical trial, and no blinding or masking will be performed. Numbers to be randomized (sample size) A total of 189 confirmed cases of COVID-19 will be randomized into seven groups. In each arm, a total of 27 participants will be recruited. Trial Status The current trial protocol is Version 1.5 from September 10, 2020. Recruitment began September 30, 2020 and is anticipated to be completed, including data analysis by February 28, 2021. Trial registration The trial protocol has been registered in the ClinicalTrials.gov on September 16, 2020. NCT Identifier number: NCT04549376. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

Using Mouthwashes by a Healthcare Practitioner in Order to Decrease the Chance of Transmission of COVID-19

2021 ◽  
Vol 7 (3) ◽  
Author(s):  
Ghasemi S ◽  
◽  
Dashti M ◽  
Keyword(s):  
Hydrogen Peroxide ◽  
Viral Load ◽  
Respiratory Tract ◽  
Influenza A ◽  
Povidone Iodine ◽  
Turn Of The Century ◽  
Water Soluble ◽  
Influenza A H1n1 ◽  
Dental Practitioners

The use of mouthwashes has shown that they can reduce the viral load of Covid-19, with the most promising mouthwashes containing hydrogen peroxide (H2O2). Cetylpyridinium Chloride (CPC), Povidone Iodine (PVP-I) and Chlorhexidine Gluconate (CHX) [1]. Since Sars-Cov-2 is transmitted by airborne droplets and the respiratory tract is the main route of infection, having a way to clear this pathway can ensure that the practitioner does not contract Covid-19 in their patients. Discussion Chlorhexidine (CHX) CHX is a wider-spectrum antiseptic that has an action on Gramnegative and Gram-positive facultative anaerobes, fungi, bacteria, and aerobes by increasing the bacterial cell wall permeability, then causing its cell lysis [2,3]. It is mainly used in dentistry procedure to treat periodontal disease and reduce dental plaque [4]. Evidence shows that an in-vitro consequence against lipidenveloped viruses likes herpesvirus 1, influenza A, cytomegalovirus, hepatitis B and parainfluenza virus [5]. Even though COVID-19 is virus with an envelope, 0.12% CHX gluconate was recommended to have no or little effect against coronaviruses when associated with other type of mouthwashes [6-8]. On the other hand, Yoon et al. [9] shown that SARS-CoV-2 suppression for two hours after consuming 15ml 0.12% CHX once, suggesting that its application would be helpful for the transmission of control of COVID-19. Hydrogen peroxide (H2O2) Since the turn of the century, H2O2 has been used in dentistry in salt combination or alone since the turn of the century [10]. Like a mouthwash, it is a clear, colorless, odorless liquid [11]. No adverse effects on soft tissue have been shown in many studies using 1-1.5 % H2O2 as a daily rinse over two years of follow-up [12,13]. An the study of in vitro study that 3% H2O2 entirely inactivates type 4 adeno-associated viruses, influenza A and B, 1B and 7 rhinoviruses, type 6 and 3 adenoviruses, type 1A, mixoviruses, respiratory syncytial virus with a long-term strain, and the Coronavirus strain 229E within 1-30 minutes, the study shows that influenza virus and coronaviruses were the most subtle [14]. Because SARS-CoV2 is susceptible to oxidation, pre-procedure mouth rinses containing oxidizing agents like the 1% H2O2 h should have reduced viral load in saliva [6,15]. Iodopovidone Povidone Iodine (PVP-I) is a iodine water-soluble mixture that is widely used as a preoperative mouthwash and skin antiseptic [16]. It is commonly used at a concentration of 1% [17] to treat mucositis, prevent ventilator-associated pneumonia and prevent oropharyngeal infections. Its antimicrobial effect is manifested after free iodine dissociates from polyvinylpyrrolidone, then iodine quickly penetrates microbes, destroying proteins and oxidizing nucleic acid structures, causing the death of microbes [18,19]. Prior studies have shown that PVP-I is more virucidal than other commonly used antiseptics, including benzalkonium chloride and CHX [20]. It is nontoxic, reporting a incidence of 0.4% of allergy cases [21], does not cause or taste disturbance and tongue or tooth discoloration [22] and, nothing like alcohol-based products, can be used along with electrocautery [23]. Its efficiency has been well revealed in many studies of in vitro against several viruses, including and influenza A (H1N1) virus SARS-CoV, and MERS-CoV [16,20,24]. Recent studies have shown that 0.23% PVP-I mouthwash perfore procedure for at least 15 seconds before can reduce viral load in saliva [24], representing its procedure in COVID patients -19 [6,18,25,26]. Effectiveness of mouthwash on viral load The Centers for Disease Control and Prevention (CDC) has long suggested taking advantage over mouthwash in reducing airborne pathogens of all kinds prior to clinical procedures [27]. During this global pandemic, given the encounters associated with dispatching dental procedure, attention has been drawn to the potential use of mouthwashes to reduce and prevent SARS-CoV-2 transmission. Conclusion Mouthwashes are an effective way to reduce the transmission of viruses that infect the respiratory tract. As oral cavities are a major source of entry and transmission for human coronaviruses, so mouthwashes are the preventive measure to reduce the risk of COVID-19. Mouthwashes, especially PVP-I, are a potential antiviral that can significantly minimize viral load in saliva and then aerosols, thereby reduce the spread of COVID-19 infection. However, there is paucity of literature and, as a result, a lack of knowledge among dental practitioners about the value of using mouthwashes. Consequently, there is a great need for more clinical trials in order to take a step forward in clinical practice.

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