scholarly journals Evaluating Diuretics in Normal Care (EVIDENCE): protocol of a cluster randomised controlled equivalence trial of prescribing policy to compare the effectiveness of thiazide-type diuretics in hypertension

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Amy Rogers ◽  
Angela Flynn ◽  
Isla S. Mackenzie ◽  
Lewis McConnachie ◽  
Rebecca Barr ◽  
...  
Keyword(s):  
Cardiovascular Death ◽  
Relative Effect ◽  
Major Adverse Cardiovascular Events ◽  
Event Analysis ◽  
Open Label ◽  
Intention To Treat ◽  
Cluster Randomised ◽  
Comparative Safety ◽  
Randomised Controlled ◽  
Primary Care Practices

Abstract Introduction Healthcare systems must use treatments that are effective and safe. Regulators licensed many currently used older medications before introducing the stringent evidential requirements imposed on modern treatments. Also, there has been little encouragement to carry out within-class, head-to-head comparisons of licensed medicines. For commonly prescribed drugs, even small differences in effectiveness or safety could have significant public health implications. However, conventional clinical trials that randomise individual subjects are costly and unwieldy. Such trials are also often criticised as having low external validity. We describe an approach to rapidly generate externally valid evidence of comparative safety and effectiveness using the example of two widely used diuretics for the management of hypertension. Methods and analysis The EVIDENCE (Evaluating Diuretics in Normal Care) study has a prospective, cluster-randomised, open-label, blinded end-point design. By randomising prescribing policy in primary care practices, the study compares the safety and effectiveness of commonly used diuretics in treating hypertension. Participating practices are randomised 1:1 to a policy of prescribing either indapamide or bendroflumethiazide when clinically indicated. Suitable patients who are not already taking the policy diuretic are switched accordingly. All patients taking the study medications are written to explaining the rationale for changing the prescribing policy and notifying them they can opt-out of any switch. The prescribing policies’ effectiveness and safety will be compared using rates of major adverse cardiovascular events (hospitalisation with myocardial infarction, heart failure or stroke or cardiovascular death), routinely collected in national healthcare administrative datasets. The study will seek to recruit 250 practices to provide a study population of approximately 50,000 individuals with a mean follow-up time of two years. A primary intention-to-treat time-to-event analysis will be used to estimate the relative effect of the two policies. Ethics and dissemination EVIDENCE has been approved by the East of Scotland Research Ethics Service (17/ES/0016, current approved protocol version 5, 26 August 2021). The results will be disseminated widely in peer reviewed journals, guideline committees, National Health Service (NHS) organisations and patient groups. Trial registration ISRCTN46635087. Registered on 11 August 2017 (pre-recruitment).

scholarly journals Evaluating Diuretics in Normal Care (EVIDENCE): Protocol of a cluster randomised controlled equivalence trial of prescribing policy to compare the effectiveness of thiazide-type diuretics in hypertension

2020 ◽  
Author(s):  
Amy Rogers ◽  
Angela Flynn ◽  
Isla S Mackenzie ◽  
Lewis McConnachie ◽  
Rebecca Barr ◽  
...  
Keyword(s):  
Primary Care ◽  
Cardiovascular Death ◽  
Major Adverse Cardiovascular Events ◽  
List Type ◽  
Primary Analysis ◽  
Open Label ◽  
Minimal Impact ◽  
Cluster Randomised ◽  
Prescribing Behaviour ◽  
Randomised Controlled

AbstractIntroductionHealthcare systems must use treatments that are effective and safe. Regulators licensed many currently used older medications before introducing the stringent evidential requirements imposed on modern treatments. Also, there has been little encouragement to carry out within-class, head-to-head comparisons of licensed medicines. For commonly prescribed drugs, even small differences in effectiveness or safety could have significant public health implications. However, conventional clinical trials that randomise individual subjects are costly and unwieldy. Such trials are also often criticised as having low external validity. We describe an approach to rapidly generate externally valid evidence of comparative safety and effectiveness using the example of two widely used diuretics for the management of hypertension.Methods and AnalysisThe EVIDENCE (Evaluating Diuretics in Normal Care) study has a prospective, cluster-randomised, open-label, blinded end-point design. By randomising prescribing policy in primary care practices, the study compares the safety and effectiveness of commonly used diuretics in treating hypertension. Participating practices are randomised 1:1 to a policy of prescribing either indapamide or bendroflumethiazide when clinically indicated. Suitable patients who are not already taking the policy diuretic are switched accordingly. All patients taking the study medications are written to explaining the rationale for changing the prescribing policy and notifying them they can opt-out of any switch. The prescribing policies’ effectiveness and safety will be compared using rates of major adverse cardiovascular events (hospitalisation with myocardial infarction, heart failure or stroke or cardiovascular death), routinely collected in national healthcare administrative datasets. The study will seek to recruit 250 practices to provide a study population of approximately 50,000 individuals with a mean follow-up time of 2 years. The primary analysis will test for equivalence with a 30% margin in a per-protocol cohort.Ethics and DisseminationEVIDENCE has been approved by the East of Scotland Research Ethics Service (17/ES/0016, current approved protocol version 4, 28th September 2019). The results will be disseminated widely in peer review journals, guideline committees, National Health Service (NHS) organisations and patient groups.Trial registration numberISRCTN 46635087; registered pre-results, 11/08/2017.Strengths and limitations of this study designA cluster randomisation design maximises generalisability of results to UK NHS primary care.Study interventions with minimal impact on existing NHS workflows should encourage recruitment.Development of electronic study search tools and routinely collected data facilitates participation by remote and rural practices.One-off policy interventions may have a limited long-term effect on prescribing behaviour.

scholarly journals Efficacy of pragmatic same-day ring prophylaxis for adult individuals exposed to SARS-CoV-2 in Switzerland (COPEP): protocol of an open-label cluster randomised trial

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e040110
Author(s):  
Mikaela Smit ◽  
Annalisa Marinosci ◽  
Giovanni Jacopo Nicoletti ◽  
Thomas Perneger ◽  
Silvio Ragozzino ◽  
...  
Keyword(s):  
Randomised Trial ◽  
Standard Of Care ◽  
Cluster Randomised Trial ◽  
Postexposure Prophylaxis ◽  
Open Label ◽  
Daily Monitoring ◽  
Intention To Treat ◽  
Cluster Randomised ◽  
Registration Number ◽  
Asymptomatic Individuals

IntroductionLopinavir/ritonavir (LPV/r) has been proposed as repurposed drugs for pre-exposure and postexposure prophylaxis as well as therapy of COVID-19. Coronavirus postexposure prophylaxis (COPEP) trial aims at assessing their efficacy as postexposure ring-prophylaxis among adults exposed to SARS-CoV-2.Methods and analysisCOPEP is a two-arm open-label cluster-randomised trial conducted in three cantons of Switzerland. Asymptomatic contacts (≥16 years) of individuals diagnosed with COVID-19 will be randomised (2:1) to either LPV/r (400 mg/100 mg two times per day) for 5 days, or a standard of care arm (no treatment). Asymptomatic individuals may be either SARS-CoV-2 positive or negative. Contacts living in the single household will form a cluster and will be randomised into the same arm. All participants will be followed-up for 21 days and undergo daily monitoring for COVID-19 symptoms. The primary endpoint is 21-day incidence of laboratory-confirmed COVID-19 with ≥1 compatible symptom, analysed in an intention-to-treat (ITT) analysis. The secondary endpoints include the 21-day incidence of COVID-19 as well as SARS-CoV-2 infection in a modified ITT analysis, excluding participants who had a positive SARS-CoV-2 RT-PCR from oropharyngeal swab and/or a positive SARS-CoV-2 IgG serology at baseline. Assuming a 21-day incidence for COVID-19 of 20% among contacts without postexposure chemoprophylaxis, to detect a relative risk reduction of 60% (ie, translating in an absolute reduction from 20% to 8%), with a power of 80%, an alpha of 5%. Accounting for design effect of cluster design of circa 1.1, we plan to enrol 200 participants to the LPV/r arm and 100 to the standard of care arm, 300 participants in total.Ethics and disseminationEthics approval has been granted by the Commission Cantonale d’Ethique de la Recherche, Ethikkommission Nordwest- und Zentralschweiz and Comitato Etico Cantonale (ref 2020-00864) and Swissmedic (2020DR3056). Results from this trial will be disseminated via journal articles and presentations at national and international conferences.Trial registration numberClinicaltrials.gov Registry (NCT04364022); Swiss National Clinical Trial Portal Registry (SNCTP 000003732).Registered report identifierCCER 2020-0864.

scholarly journals A cluster randomised controlled trial to determine the effect of community mobilisation and advocacy on men’s use of violence in periurban South Africa: study protocol

BMJ Open ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. e017579 ◽  
Author(s):  
Nicola J Christofides ◽  
Abigail M Hatcher ◽  
Angelica Pino ◽  
Dumisani Rebombo ◽  
Ruari Santiago McBride ◽  
...  
Keyword(s):  
South Africa ◽  
Randomised Controlled Trial ◽  
Alcohol Use ◽  
Controlled Trial ◽  
Cluster Randomised Controlled Trial ◽  
Computer Assisted ◽  
Community Mobilisation ◽  
Intention To Treat ◽  
Cluster Randomised ◽  
Randomised Controlled

ObjectiveThis paper describes the design and methods of a cluster randomised controlled trial (C-RCT) to determine the effectiveness of a community mobilisation intervention that is designed to reduce the perpetration of violence against women (VAW).Methods and analysisA C-RCT of nine intervention and nine control clusters is being carried out in a periurban, semiformal settlement near Johannesburg, South Africa, between 2016 and 2018. A community mobilisation and advocacy intervention, called Sonke CHANGE is being implemented over 18 months. It comprises local advocacy and group activities to engage community members to challenge harmful gender norms and reduce VAW. The intervention is hypothesised to improve equitable masculinities, reduce alcohol use and ultimately, to reduce VAW. Intervention effectiveness will be determined through an audio computer-assisted self-interview questionnaire with behavioural measures among 2600 men aged between 18 and 40 years at baseline, 12 months and 24 months. The primary trial outcome is men’s use of physical and/or sexual VAW. Secondary outcomes include harmful alcohol use, gender attitudes, controlling behaviours, transactional sex and social cohesion. The main analysis will be intention-to-treat based on the randomisation of clusters. A qualitative process evaluation is being conducted alongside the C-RCT. Implementers and men participating in the intervention will be interviewed longitudinally over the period of intervention implementation and observations of the workshops and other intervention activities are being carried out.Ethics and disseminationEthical approval was obtained from the University of the Witwatersrand Human Research Ethics Committee and procedures comply with ethical recommendations of the United Nations Multi-Country Study on Men and Violence. Dissemination of research findings will take place with local stakeholders and through peer-reviewed publications, with data available on request or after 5 years of trial completion.Trial registration numberNCT02823288; Pre-result.

Hybrid minimally invasive versus open oesophagectomy for patients with oesophageal cancer: A multicenter, open-label, randomized phase III controlled trial, the MIRO trial.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 5-5 ◽  
Author(s):  
Christophe Mariette ◽  
Bernard Meunier ◽  
Denis Pezet ◽  
Cecile Dalban ◽  
Denis Collet ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Oesophageal Cancer ◽  
Postoperative Morbidity ◽  
Controlled Trial ◽  
Pulmonary Complications ◽  
Phase Iii ◽  
Open Label ◽  
Intention To Treat ◽  
Randomised Controlled ◽  
Minimally Invasive Oesophagectomy

5 Background: Surgical resection is regarded as the only curative option for resectable oesophageal cancer. Postoperative morbidity, in particular pulmonary complications, continues to be of great concern and occurs in more than half of patients after open oesophagectomy (OO). We assessed whether hybrid minimally invasive oesophagectomy (HMIO) reduces morbidity compared with OO. Methods: We performed a multicentre, open-label, randomised controlled trial at 12 study centres between October 2009 and April 2012. Patients aged 18-75 years old with resectable cancers of the middle or lower third of the oesophagus were assigned by a computer-generated randomisation sequence to undergo either transthoracic OO or HMIO. Surgical technique was standardised by both on site visits and the use of videos, and was based on an Ivor Lewis procedure with laparoscopic gastric mobilisation and open right thoracotomy. Randomisation was stratified by centre. The primary outcome was 30 day grade II-IV postoperative morbidity as defined by the Dindo-Clavien classification. Analysis was by intention to treat. Results: We randomly assigned 104 patients to the OO group and 103 to the HMIO group. Sixty-seven (64.4%) patients in the OO group had major postoperative morbidity compared with 37 (35.9%) in the HMIO group (OR 0·31, 95% CI 0·18-0·55; p=0·0001). Thirty-one (30.1%) patients in the OO had major pulmonary complications compared with 18 (17.7%) in the minimally invasive group p=0·037), whereas 30-day mortality was 5 (4.9%) vs. 5 (4.9%), respectively. Conclusions: These findings provide evidence for the short-term benefits of HMIO for patients with resectable oesophageal cancer (NCT00937456 ClinicalTrials.gov). Clinical trial information: NCT00937456.

Comparison of two dose escalation strategies of methotrexate in active rheumatoid arthritis: a multicentre, parallel group, randomised controlled trial

2021 ◽  
pp. annrheumdis-2021-220512
Author(s):  
Siddharth Jain ◽  
Varun Dhir ◽  
Amita Aggarwal ◽  
Ranjan Gupta ◽  
Bidyalaxmi Leishangthem ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Controlled Trial ◽  
Group Differences ◽  
Drug Discontinuation ◽  
Open Label ◽  
Intention To Treat ◽  
Parallel Group ◽  
Registration Number ◽  
Randomised Controlled

ObjectivesThere are no head-to-head trials of different dose escalation strategies of methotrexate (MTX) in RA. We compared the efficacy, safety and tolerability of ‘usual’ (5 mg every 4 weeks) versus ‘fast’ (5 mg every 2 weeks) escalation of oral MTX.MethodsThis multicentre, open-label (assessor blinded) RCT included patients 18-55 years of age having active RA with disease duration <5 years, and not on DMARDs. Patients were randomized 1:1 into usual or fast escalation groups, both groups starting MTX at 15 mg/week till a maximum of 25 mg/week. Primary outcome was EULAR good response at 16 weeks, secondary outcomes were ΔDAS28 and adverse effects (AE). Analyses were intention-to-treat.Results178 patients with mean DAS28-CRP of 5.4(1.1) were randomized to usual (n=89) or fast escalation groups (n=89). At 16 weeks, there was no difference in good EULAR response in the usual (28.1%) or fast escalation (22.5%) groups (p=0.8). There was no difference in mean ΔDAS28-CRP at 8 weeks (-0.9, -0.8, p=0.72) or 16 weeks (-1.3, -1.3, p=0.98). Even at 24 weeks (extended follow-up), responses were similar. There were no inter-group differences in ΔHAQ, or MTX-polyglutamates 1-3 levels at 8 or 16 weeks. Gastrointestinal AE were higher in the fast escalation group over initial 8 weeks (27%, 40%, p=0.048), but not over 16 weeks. There was no difference in cytopenias, transaminitis, or drug discontinuation/dose reduction between the groups. No serious AE were seen.ConclusionA faster MTX escalation strategy in RA was not more efficacious over 16-24 weeks, and did not significantly increase AE, except higher gastrointestinal AE initially.Trial registration numberCTRI/2018/12/016549

Clinical effectiveness of a Malaysian-manufactured CAPD product: A randomised trial

2021 ◽  
Vol 41 (3) ◽  
pp. 273-283 ◽  
Author(s):  
Wen Yao Mak ◽  
Chin Tho Leong ◽  
Loke Meng Ong ◽  
Sunita Bavanandan ◽  
Lily Mushahar ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Randomised Trial ◽  
Clinical Effectiveness ◽  
Open Label ◽  
Dialysis Dose ◽  
Intention To Treat ◽  
Significant Difference ◽  
Incident Rate ◽  
Randomised Controlled

Background:We compared the clinical effectiveness of a new peritoneal dialysis (PD) product with polyvinyl chloride-containing tubing (Stay Safe Link®, SSL) with the plastic-free alternative (Stay Safe®, STS) in patients on continuous ambulatory peritoneal dialysis (CAPD).Method:A multicentre, parallel, randomised, controlled, open-label, non-inferiority trial was conducted. Adult patients receiving CAPD were randomised in a 1:1 ratio to SSL or STS. The primary outcome was the rate of peritonitis after 1 year of follow-up.Results:A total of 472 subjects were randomised (SSL, n = 233; STS, n = 239). One subject in each group was excluded from the analysis as they withdrew consent before the first dialysis dose. Four hundred and seventy subjects (SSL, n = 232; STS, n = 238) were included in the modified intention-to-treat analysis. Non-inferiority between two groups was established as no significant difference was found in peritonitis rate (incident rate ratio: 0.91, 95% CI: 0.65–1.28). No significant difference was detected in weekly Kt/V ( p = 0.58) and creatinine clearance ( p = 0.55). However, the average ultrafiltration volume was significantly lower in SSL, with a mean difference of 93 ml ( p < 0.01). SSL also demonstrated a 2.57-times higher risk of device defect than STS (95% CI: 1.77–3.75).Conclusion:SSL was non-inferior in peritonitis rate compared to plastic-free STS over 1 year in patients requiring CAPD. There was no difference in the delivered dialysis dose, but there was a higher rate of device defects with SSL.

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