ABSTRACT
BACKGROUND: There is a lack of randomised controlled trials (RCTs) investigating the role of hand hygiene in preventing and containing acute respiratory infections (ARIs) in mass gatherings. In this pilot RCT, we assessed the feasibility of establishing a large-scale trial to explore the relationship between practising hand hygiene and rates of ARI in Umrah pilgrimage amidst the COVID-19 pandemic. METHODS: A parallel RCT was conducted in hotels in Makkah, Saudi Arabia, between April and July 2021. Domestic adult pilgrims who consented to participate were randomised 1:1 to the intervention group who received alcohol-based hand rub (ABHR) and instructions, or to the control group who did not receive ABHR or instructions but were free to use their own supplies. Pilgrims in both groups were then followed up for seven days for ARI symptoms. The primary outcome was the difference in the proportions of syndromic ARIs among pilgrims between the randomised groups. RESULTS: A total of 507 (control: intervention = 267: 240) participants aged between 18 and 75 (median 34) years were randomised; 61 participants were lost to follow-up or withdrew leaving 446 participants (control: intervention = 237:209) for the primary outcome analysis; of whom 10 (2.2 %) had developed at least one respiratory symptom, three (0.7 %) had 'possible ILI' and two (0.4 %) had 'possible COVID-19'. The analysis of the primary outcome found no evidence of difference in the proportions of ARIs between the randomised groups (odds ratio 1.1 [0.3-4.0] for intervention relative to control). CONCLUSION: This pilot trial suggests that conducting a future definitive RCT to assess the role of hand hygiene in the prevention of ARIs is feasible in Umrah setting amidst such a pandemic; however, outcomes from this trial are inconclusive, and such a study would need to be very large given the low rates of outcomes observed here. TRIAL REGISTRATION: This trial was registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12622001287729), the full protocol can be accessed there.
ABSTRACT
INTRODUCTION: There has been renewed interest in the therapeutic use of bacteriophages (phages); however, standardised therapeutic protocols are lacking, and there is a paucity of rigorous clinical trial data assessing efficacy. METHODS AND ANALYSIS: We propose an open-label, single-arm trial investigating a standardised treatment and monitoring protocol for phage therapy. Patients included will have exhausted other therapeutic options for control of their infection and phage therapy will be administered under Australia's Therapeutic Goods Administration Special Access Scheme. A phage product with high in vitro activity against the targeted pathogen(s) must be available in line with relevant regulatory requirements. We aim to recruit 50-100 patients over 5 years, from any public or private hospitals in Australia. The standardised protocol will specify clinical assessments and biological sampling at scheduled time points. The primary outcome is safety at day 29, assessed by the frequency of adverse events, and overseen by an independent Data Safety Monitoring Board. Secondary outcomes include long-term safety (frequency of adverse events until at least 6 months following phage therapy), and feasibility, measured as the proportion of participants with>80% of minimum data available for analysis. Additional endpoints assessed include clinical response, patient/guardian reported quality of life measures, phage pharmacokinetics, human host immune responses and microbiome analysis. All trial outcomes will be summarised and presented using standard descriptive statistics. ETHICS AND DISSEMINATION: Participant inclusion will be dependent on obtaining written informed consent from the patient or guardian. The trial protocol was approved by the Sydney Children's Hospitals Network Human Research Ethics Committee in December 2021 (Reference 2021/ETH11861). In addition to publication in a peer-reviewed scientific journal, a lay summary of study outcomes will be made available for participants and the public on the Phage Australia website (https://www.phageaustralia.org/). TRIAL REGISTRATION NUMBER: Registered on ANZCTR, 10 November 2021 (ACTRN12621001526864; WHO Universal Trial Number: U1111-1269-6000).
Subject(s)
COVID-19 , Phage Therapy , Adult , Child , Humans , Quality of Life , SARS-CoV-2 , Treatment OutcomeABSTRACT
BACKGROUND: In this large-scale cluster-randomized controlled trial (cRCT) we sought to assess the effectiveness of facemasks against viral respiratory infections. METHODS AND RESULTS: Over three consecutive Hajj seasons (2013, 2014, 2015) pilgrims' tents in Makkah were allocated to 'facemask' or 'no facemask' group. Fifty facemasks were offered to participants in intervention tents, to be worn over four days, and none were offered to participants in control tents. All participants recorded facemask use and respiratory symptoms in health diaries. Nasal swabs were collected from the symptomatic for virus detection by reverse transcription polymerase chain reaction. Clinical symptoms and laboratory results were analyzed by 'intention- to-treat' and 'per-protocol'. A total of 7687 adult participants from 318 tents were randomized: 3864 from 149 tents to the intervention group, and 3823 from 169 tents to the control group. Participants were aged 18 to 95 (median 34, mean 37) years, with a male to female ratio of 1:1.2. Overall, respiratory viruses were detected in 277 of 650 (43%) nasal/pharyngeal swabs collected from symptomatic pilgrims. Common viruses were rhinovirus (35.1%), influenza (4.5%) and parainfluenza (1.7%). In the intervention arm, respectively 954 (24.7%) and 1842 (47.7%) participants used facemasks daily and intermittently, while in the control arm, respectively 546 (14.3%) and 1334 (34.9%) used facemasks daily and intermittently. By intention-to-treat analysis, facemask use did not seem to be effective against laboratory-confirmed viral respiratory infections (odds ratio [OR], 1.4; 95% confidence interval [CI], 0.9 to 2.1, p = 0.18) nor against clinical respiratory infection (OR, 1.1; 95% CI, 0.9 to 1.4, p = 0.40). Similarly, in a per-protocol analysis, facemask use did not seem to be effective against laboratory-confirmed viral respiratory infections (OR 1.2, 95% CI 0.9-1.7, p = 0.26) nor against clinical respiratory infection (OR 1.3, 95% CI 1.0-1.8, p = 0.06). CONCLUSION: This trial was unable to provide conclusive evidence on facemask efficacy against viral respiratory infections most likely due to poor adherence to protocol.