A Phase II randomised controlled trial of oral prednisolone in early diffuse cutaneous systemic sclerosis (PRedSS).

OBJECTIVES: Although the painful and disabling features of early diffuse cutaneous systemic sclerosis (dcSSc) have an inflammatory basis and could respond to corticosteroids, corticosteroids are a risk factor for scleroderma renal crisis. Whether or not they should be prescribed is therefore highly contentious. Our aim was to examine safety and efficacy of moderate dose prednisolone in early dcSSc. METHODS: PRedSS set out as a Phase II, multicentre, double-blind randomised controlled trial, converted to open-label during the Covid-19 pandemic. Patients were randomised to receive either prednisolone (∼0.3 mg/kg) or matching placebo (or no treatment during open-label) for 6 months. Co-primary endpoints were the Health Assessment Questionnaire Disability Index (HAQ-DI) and modified Rodnan skin core (mRSS) at 3 months. Over 20 secondary endpoints included patient reported outcome measures reflecting pain, itch, fatigue, anxiety and depression, and helplessness. Target recruitment was 72 patients. RESULTS: Thirty-five patients were randomised (17 prednisolone, 18 placebo/control). The adjusted mean difference between treatment groups at 3 months in HAQ-DI score was -0.10 (97.5% CI -0.29-0.10), p= 0.254, and in mRSS -3.90 (97.5% CI -8.83-1.03), p= 0.070, both favouring prednisolone but not significantly. Patients in the prednisolone group experienced significantly less pain (p= 0.027), anxiety (p= 0.018) and helplessness (p= 0.040) than control patients at 3 months. There were no renal crises, but sample size was small. CONCLUSION: PRedSS was terminated early primarily due to the Covid-19 pandemic, and so was underpowered. Therefore, interpretation must be cautious and results considered inconclusive, indicating the need for a further randomised trial. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03708718.

Systematic voiding programme in adults with urinary incontinence following acute stroke: the ICONS-II RCT.

BACKGROUND: Urinary incontinence affects around half of stroke survivors in the acute phase, and it often presents as a new problem after stroke or, if pre-existing, worsens significantly, adding to the disability and helplessness caused by neurological deficits. New management programmes after stroke are needed to address urinary incontinence early and effectively. OBJECTIVE: The Identifying Continence OptioNs after Stroke (ICONS)-II trial aimed to evaluate the clinical effectiveness and cost-effectiveness of a systematic voiding programme for urinary incontinence after stroke in hospital. DESIGN: This was a pragmatic, multicentre, individual-patient-randomised (1 : 1), parallel-group trial with an internal pilot. SETTING: Eighteen NHS stroke services with stroke units took part. PARTICIPANTS: Participants were adult men and women with acute stroke and urinary incontinence, including those with cognitive impairment. INTERVENTION: Participants were randomised to the intervention, a systematic voiding programme, or to usual care. The systematic voiding programme comprised assessment, behavioural interventions (bladder training or prompted voiding) and review. The assessment included evaluation of the need for and possible removal of an indwelling urinary catheter. The intervention began within 24 hours of recruitment and continued until discharge from the stroke unit. MAIN OUTCOME MEASURES: The primary outcome measure was severity of urinary incontinence (measured using the International Consultation on Incontinence Questionnaire) at 3 months post randomisation. Secondary outcome measures were taken at 3 and 6 months after randomisation and on discharge from the stroke unit. They included severity of urinary incontinence (at discharge and at 6 months), urinary symptoms, number of urinary tract infections, number of days indwelling urinary catheter was in situ, functional independence, quality of life, falls, mortality rate and costs. The trial statistician remained blinded until clinical effectiveness analysis was complete. RESULTS: The planned sample size was 1024 participants, with 512 allocated to each of the intervention and the usual-care groups. The internal pilot did not meet the target for recruitment and was extended to March 2020, with changes made to address low recruitment. The trial was paused in March 2020 because of COVID-19, and was later stopped, at which point 157 participants had been randomised (intervention, n = 79; usual care, n = 78). There were major issues with attrition, with 45% of the primary outcome data missing: 56% of the intervention group data and 35% of the usual-care group data. In terms of the primary outcome, patients allocated to the intervention group had a lower score for severity of urinary incontinence (higher scores indicate greater severity in urinary incontinence) than those allocated to the usual-care group, with means (standard deviations) of 8.1 (7.4) and 9.1 (7.8), respectively. LIMITATIONS: The trial was unable to recruit sufficient participants and had very high attrition, which resulted in seriously underpowered results. CONCLUSIONS: The internal pilot did not meet its target for recruitment and, despite recruitment subsequently being more promising, it was concluded that the trial was not feasible owing to the combined problems of poor recruitment, poor retention and COVID-19. The intervention group had a slightly lower score for severity of urinary incontinence at 3 months post randomisation, but this result should be interpreted with caution. FUTURE WORK: Further studies to assess the effectiveness of an intervention starting in or continuing into the community are required. TRIAL REGISTRATION: This trial is registered as ISRCTN14005026. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 31. See the NIHR Journals Library website for further project information.

Urinary incontinence affects around half of stroke survivors. It causes embarrassment and distress, affecting patients' ability to take part in rehabilitation. It also has a major impact on families and may determine whether or not patients are able to return home. Finding the underlying cause and addressing it can prevent, cure or reduce problems. Doing this in a systematic way for everyone with incontinence problems as early as possible after the stroke, while they are still in hospital, may work best. We also wanted to avoid using catheters in the bladder to drain the urine away, as these are often unnecessary and can cause urinary tract infections. This study aimed to test whether or not continence problems and the use of urinary catheters could be reduced if everyone with incontinence was fully assessed and given the right management and support early after hospital admission. We also wanted to find out if the benefits outweighed the costs. We planned to involve 1024 men and women with incontinence from 18 stroke units in the study, with 512 people receiving the intervention and 512 receiving usual care. However, the trial was paused because of COVID-19, at which time only 157 participants had been recruited. When we were thinking about restarting the study and looked at its progress, we found that not enough people had agreed to take part and, of those who had agreed, many had not returned their outcome questionnaires. This indicated that the trial was not feasible and should not restart. We could not make any firm conclusions about whether or not the intervention worked, as not enough people were involved. We found that stays in hospital after stroke are shorter than they were in the past. This suggests that future studies investigating ways of treating incontinence should consider interventions with management and support for incontinence that continue after patients leave the hospital.