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Lookup NU author(s): Helen MossopORCiD, Dr Emma ClarkORCiD, Gillian WatsonORCiD, Professor Miles WithamORCiD, Professor Luke Vale, Dr Naomi McGregorORCiD, Julia PhillipsonORCiD, Professor James WasonORCiD, Professor Alison YarnallORCiD, Professor Helen HancockORCiD, Professor Rose Anne Kenny, Dr James FrithORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Background: Orthostatic hypotension is a significant drop in blood pressure upon standing upright. It is very common and can result in symptoms such as postural dizziness, fainting and falls. Within the United Kingdom National Health Service, there are three principal treatments: non-drug therapies, and two medications - fludrocortisone or midodrine. Despite this we do not know which treatments are the most effective, nor whether they are cost-effective. Objective: Evaluate the feasibility of a randomised trial to evaluate the clinical and cost-effectiveness of fludrocortisone and midodrine in comparison to non-drug therapies for the treatment of orthostatic hypotension. Design: A 10-month pilot of a pragmatic, open-label, randomised, prospective, superiority, multiarm, multistage clinical trial. The pilot evaluated recruitment, attrition, crossover and quality of outcomes. Setting: Falls and Syncope, Movement Disorder, Geriatrics, and Cardiology clinics in United Kingdom National Health Service secondary care. Participants: Adults with symptomatic orthostatic hypotension. Interventions: Control: Non-drug therapies (conservative management). Interventions: Conservative management plus fludrocortisone (50-400 mcg daily) or conservative management plus midodrine (5-30 mg daily). Main outcome measures: Recruitment: Target was 40-64 participants from 14 sites. Attrition target: ≤ 15% participants withdraw before the primary end point. Crossover: To determine the rates of crossover between intervention arms. Outcome data: Assess the quality and completeness of outcomes. Other important outcomes included feedback via questionnaire and interview from sites and participants. Results: Two hundred and eighty-two patients were screened for eligibility during the pilot; of these, 13 were recruited from 4 of 9 open sites. Current or recent use of one of the study medications accounted for 120 (52%) exclusions due to ineligibility. At the primary end point of 6 months, 10 of the 13 participants (77%) remained in the study. Of those, completion rates for primary and secondary outcomes were 100%, except for the falls diaries, which was 60%. Feedback from sites revealed that redeployment of clinical and research staff due to COVID-19 negatively impacted on site opening and screening for eligible participants. Adapting the protocol to make it more flexible for remote clinics and more pragmatic for clinical use did not improve recruitment. Limitations: The sample size is too small to provide a reliable estimate of attrition and crossover rates for future studies. Conclusions: This study was not feasible in its current design. COVID-19 had an impact on staffing and site opening, while the exclusion criteria limited recruitment. Future work: To answer the research question, novel trial designs are needed. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR127385.Orthostatic hypotension is a large drop in blood pressure which occurs on standing upright. It is very common but the best way to treat it is not known. This clinical trial aimed to find out whether three common treatments help to improve the condition and are value for money. The treatments were non-drug therapies (such as water and salt and compression garments) and two medications – fludrocortisone and midodrine. The trial included a 10-month pilot (rehearsal) to see whether a full trial would be feasible. The pilot evaluated how many participants it was possible to recruit, how many dropped out and whether participants changed their allocated treatment. The outcomes (which measure if a treatment is effective) were evaluated to see how well they were completed. Feedback was gained from the NHS hospital sites that were involved and the participants who volunteered. The study began in November 2019. The UK went into lockdown for the COVID-19 pandemic in March 2020. This resulted in delays to the start of the trial and a shortage of staff available to work on the study. At the end of the pilot, 282 adults with OH had been identified at nine sites across the UK. Of these, 233 did not meet the criteria to take part. For just over half (52%), this was because they were already taking one of the study treatments. In 9 months, only 13 participants had been recruited (the target was at least 40). Of these, 3 dropped out so results were available in 10 participants at 6 months. The number of participants is too small to measure how effective the treatments are. To answer the research question a clinical trial would need to be designed differently, focusing on ways to recruit more participants and support clinical staff to deliver the study.
Author(s): Mossop H, Al Ashmori S, Sotire T, Clark E, Watson G, Witham M, Vale L, McGregor N, Phillipson J, Wason JM, Yarnall AJ, Hancock H, Kenny RA, Frith J
Publication type: Article
Publication status: Published
Journal: Health Technology Assessment
Year: 2025
Volume: 29
Issue: 54
Pages: 1-21
Print publication date: 01/11/2025
Acceptance date: 02/04/2018
Date deposited: 27/11/2025
ISSN (print): 1366-5278
ISSN (electronic): 2046-4924
Publisher: NIHR Journals Library
URL: https://doi.org/10.3310/HGRW7249
DOI: 10.3310/HGRW7249
PubMed id: 41217271
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