Type of publication:
Journal article
Author(s):
Knowles, Charles H; Booth, Lesley; Brown, Steve R; Cross, Samantha; Eldridge, Sandra; Emmett, Christopher; Grossi, Ugo; Jordan, Mary; *Lacy-Colson, Jon; Mason, James; McLaughlin, John; Moss-Morris, Rona; Norton, Christine; Scott, S Mark; Stevens, Natasha; Taheri, Shiva; Yiannakou, Yan.
Citation:
NIHR Journals Library. Programme Grants for Applied Research 2021 Vol 9(14).
Abstract:
BACKGROUND: Chronic constipation affects 1-2% of adults and significantly affects quality of life. Beyond the use of laxatives and other basic measures, there is uncertainty about management, including the value of specialist investigations, equipment-intensive therapies using biofeedback, transanal irrigation and surgery. OBJECTIVES: (1) To determine whether or not standardised specialist-led habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback is more clinically effective than standardised specialist-led habit training alone, and whether or not outcomes of such specialist-led interventions are improved by stratification to habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback or habit training alone based on prior knowledge of anorectal and colonic pathophysiology using standardised radiophysiological investigations; (2) to compare the impact of transanal irrigation initiated with low-volume and high-volume systems on patient disease-specific quality of life; and (3) to determine the clinical efficacy of laparoscopic ventral mesh rectopexy compared with controls at short-term follow-up. DESIGN: The Chronic Constipation Treatment Pathway (CapaCiTY) research programme was a programme of national recruitment with a standardised methodological framework (i.e. eligibility, baseline phenotyping and standardised outcomes) for three randomised trials: a parallel three-group trial, permitting two randomised comparisons (CapaCiTY trial 1), a parallel two-group trial (CapaCiTY trial 2) and a stepped-wedge (individual-level) three-group trial (CapaCiTY trial 3). SETTING: Specialist hospital centres across England, with a mix of urban and rural referral bases. PARTICIPANTS: The main inclusion criteria were as follows: age 18-70 years, participant self-reported problematic constipation, symptom onset > 6 months before recruitment, symptoms meeting the American College of Gastroenterology's constipation definition and constipation that failed treatment to a minimum basic standard. The main exclusion criteria were secondary constipation and previous experience of study interventions. INTERVENTIONS: CapaCiTY trial 1: group 1 – standardised specialist-led habit training alone (n = 68); group 2 – standardised specialist-led habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback (n = 68); and group 3 – standardised radiophysiological investigations-guided treatment (n = 46) (allocation ratio 3 : 3 : 2, respectively). CapaCiTY trial 2: transanal irrigation initiated with low-volume (group 1, n = 30) or high-volume (group 2, n = 35) systems (allocation ratio 1 : 1). CapaCiTY trial 3: laparoscopic ventral mesh rectopexy performed immediately (n = 9) and after 12 weeks' (n = 10) and after 24 weeks' (n = 9) waiting time (allocation ratio 1 : 1 : 1, respectively). MAIN OUTCOME MEASURES: The main outcome measures were standardised outcomes for all three trials. The primary clinical outcome was mean change in Patient Assessment of Constipation Quality of Life score at the 6-month, 3-month or 24-week follow-up. The secondary clinical outcomes were a range of validated disease-specific and psychological scoring instrument scores. For cost-effectiveness, quality-adjusted life-year estimates were determined from individual participant-level cost data and EuroQol-5 Dimensions, five-level version, data. Participant experience was investigated through interviews and qualitative analysis. RESULTS: A total of 275 participants were recruited. Baseline phenotyping demonstrated high levels of symptom burden and psychological morbidity. CapaCiTY trial 1: all interventions (standardised specialist-led habit training alone, standardised specialist-led habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback and standardised radiophysiological investigations-guided habit training alone or habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback) led to similar reductions in the Patient Assessment of Constipation Quality of Life score (approximately -0.8 points), with no statistically significant difference between habit training alone and habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback (-0.03 points, 95% confidence interval -0.33 to 0.27 points; p = 0.8445) or between standardised radiophysiological investigations and no standardised radiophysiological investigations (0.22 points, 95% confidence interval -0.11 to 0.55 points; p = 0.1871). Secondary outcomes reflected similar levels of benefit for all interventions. There was no evidence of greater cost-effectiveness of habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback or stratification by standardised radiophysiological investigations compared with habit training alone (with the probability that habit training alone is cost-effective at a willingness-to-pay threshold of 30,000 per quality-adjusted life-year gain; p = 0.83). Participants reported mixed experiences and similar satisfaction in all groups in the qualitative interviews. CapaCiTY trial 2: at 3 months, there was a modest reduction in the Patient Assessment of Constipation Quality of Life score, from a mean of 2.4 to 2.2 points (i.e. a reduction of 0.2 points), in the low-volume transanal irrigation group compared with a larger mean reduction of 0.6 points in the high-volume transanal irrigation group (difference -0.37 points, 95% confidence interval -0.89 to 0.15 points). The majority of participants preferred high-volume transanal irrigation, with substantial crossover to high-volume transanal irrigation during follow-up. Compared with low-volume transanal irrigation, high-volume transanal irrigation had similar costs (median difference -8, 95% confidence interval -240 to 221) and resulted in significantly higher quality of life (0.093 quality-adjusted life-years, 95% confidence interval 0.016 to 0.175 quality-adjusted life-years). CapaCiTY trial 3: laparoscopic ventral mesh rectopexy resulted in a substantial short-term mean reduction in the Patient Assessment of Constipation Quality of Life score (-1.09 points, 95% confidence interval -1.76 to -0.41 points) and beneficial changes in all other outcomes; however, significant increases in cost (5012, 95% confidence interval 4446 to 5322) resulted in only modest increases in quality of life (0.043 quality-adjusted life-years, 95% confidence interval -0.005 to 0.093 quality-adjusted life-years), with an incremental cost-effectiveness ratio of 115,512 per quality-adjusted life-year. CONCLUSIONS: Excluding poor recruitment and underpowering of clinical effectiveness analyses, several themes emerge: (1) all interventions studied have beneficial effects on symptoms and disease-specific quality of life in the short term; (2) a simpler, cheaper approach to nurse-led behavioural interventions appears to be at least as clinically effective as and more cost-effective than more complex and invasive approaches (including prior investigation); (3) high-volume transanal irrigation is preferred by participants and has better clinical effectiveness than low-volume transanal irrigation systems; and (4) laparoscopic ventral mesh rectopexy in highly selected participants confers a very significant short-term reduction in symptoms, with low levels of harm but little effect on general quality of life. LIMITATIONS: All three trials significantly under-recruited [CapaCiTY trial 1, n = 182 (target 394); CapaCiTY trial 2, n = 65 (target 300); and CapaCiTY trial 3, n = 28 (target 114)]. The numbers analysed were further limited by loss before primary outcome. TRIAL REGISTRATION: Current Controlled Trials ISRCTN11791740,
ISRCTN11093872 and ISRCTN11747152.
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