Control, Fludrocortisone or Midodrine for the treatment of Orthostatic Hypotension (CONFORM-OH): Results from an internal pilot randomised controlled trial

Background Orthostatic hypotension (OH) is a common debilitating condition characterised by a significant drop in blood pressure (BP) on standing upright. Adults with OH are typically offered non-pharmacologic therapies, either alone or in combination with medication. The two most used agents are fludrocortisone and midodrine. There is a lack of good quality evidence for any of these treatments, all of which are in widespread clinical use. The aim of this internal pilot trial was to evaluate recruitment, attrition, treatment crossover and quality of outcomes. Methods The trial was designed as a pragmatic, open label, randomised, prospective, multicentre, superiority, multi-arm internal pilot. Within the 10-month pilot, a target of 64 adults with OH from 14 sites, was required to evaluate feasibility of recruitment, attrition, crossover and data collection. Participants were randomised to one of three treatments: non-drug therapies (control), fludrocortisone plus non-drug therapies or midodrine plus non-drug therapies. Outcomes measured included symptoms, quality of life, activities of daily living, postural BP, use of health and care services, falls and safety. Participants received treatment and were followed-up for 12 months. Pre-planned criteria to progress from internal pilot were defined for recruitment, retention, crossover and outcome completion. Results Between the 3 rd December 2021 and 31 st August 2022, 13 participants were randomised from four of nine recruiting centres. Redeployment of clinical and research staff, due to COVID-19, limited the number of available sites. Participants already receiving fludrocortisone or midodrine accounted for 120 of 233 eligible participants being excluded. Due to the low sample size the rates of attrition and crossover are of limited value. Apart from the falls diaries, completion rates of the outcome measures were high. Due to low recruitment rates the pilot did not progress to the planned multi-arm multi-stage trial. Conclusions In its current design, this trial was not feasible. The main barriers to success were participants already receiving treatment and redeployment of clinical and academic staff during and after the COVID-19 pandemic. Trial registration ISRCTN 87213295, 23/07/2021, https://doi.org/10.1186/ISRCTN87213295 Key messages regarding feasibility The clinical and cost effectiveness of different treatment strategies for orthostatic hypotension is unknown. People with orthostatic hypotension tend to be older, have multiple long-term conditions and take multiple medications. There is uncertainty around recruitment of this population, attrition rates, potential crossover of treatments and completion of multiple outcome measures. Redeployment of clinical and research staff during COVID-19 and the post-COVID period meant that trial delivery was not feasible. Recent or current exposure to one of the trial interventions precluded a large proportion of participants being eligible. A flexible and pragmatic trial protocol was not sufficient to overcome these barriers. The number and timing of outcome measures appears to be appropriate and feasible.