Constipation

Non-drug therapies for the management of chronic constipation in adults: the CapaCiTY research programme including three RCTs (2021)

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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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Stepped-wedge randomised trial of laparoscopic ventral mesh rectopexy in adults with chronic constipation: A randomised controlled trial (2020)

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Type of publication:
Conference abstract

Author(s):
Grossi U.; McAlees E.; Knowles C.H.; Stevens N.; Di Tanna G.L.; Marlin N.; *Lacy-Colson J.; Brown S.; Scott S.M.; Norton C.; Mason J.

Citation:
Techniques in Coloproctology; 2020; vol. 24 (no. 4); p. 373-374

Abstract:
Background: Laparoscopic ventral mesh rectopexy (LVMR) is an established treatment for external full-thickness rectal prolapse. However, its clinical efficacy in patients with internal prolapse is uncertain due to the lack of high-quality evidence.
Methods: An individual level, stepped-wedge randomised trial has been designed to allow observer blinded data comparisons between patients awaiting LVMR with those who have undergone surgery. Adults with symptomatic internal rectal prolapse, unresponsive to prior conservative management, will be eligible to participate. They will be randomised to three arms with different delays before surgery (0, 12 and 24 weeks). Efficacy outcome data will be collected at equally stepped time points (12, 24, 36 and 48 weeks). The primary objective is to determine clinical efficacy of LVMR compared to controls with reduction in the Patient Assessment of Constipation Quality of Life (PAC-QOL) at 24 weeks serving as the primary outcome. Secondary objectives are to determine: (1) the clinical effectiveness of LVMR to 48 weeks to a maximum of 72 weeks; (2) preoperative determinants of outcome; (3) relevant health economics for LVMR; (4) qualitative evaluation of patient and health professional experience of LVMR and (5) 30-day morbidity and mortality rates.
Results: An individual-level, stepped-wedge, randomised trial serves the purpose of providing an untreated comparison for the active treatment group, while at the same time allowing the waiting-listed participants an opportunity to obtain the intervention at a later date. Conclusions: In keeping with the basic ethical tenets of this design, the average waiting time for LVMR (12 weeks) will be shorter than that for routine services (24 weeks).

Surgery for constipation: systematic review and practice recommendations: Results II: Hitching procedures for the rectum (2017)

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Type of publication:
Systematic Review

Author(s):
Grossi U.; Knowles C.H.; Mason J.; *Lacy-Colson J.; Brown S.R.; Campbell K.; Chapman M.; Clarke A.; Cruickshank

Citation:
Colorectal Disease; Sep 2017; vol. 19 ; p. 37-48

Abstract:
Aim: To assess the outcomes of rectal suspension procedures (forms of rectopexy) in adults with chronic constipation. Method: Standardised methods and reporting of benefits and harms were used for all Capacity reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements with a summative Oxford Centre for Evidence-Based Medicine (2009) level. Results: Eighteen articles were identified, providing data on outcomes in 1238 patients. All studies reported only on laparoscopic approaches. Length of procedures ranged between 1.5 to 3.5 h, and length of stay between 4 to 5 days. Data on harms were inconsistently reported and heterogeneous, making estimates of harm tentative and imprecise. Morbidity rates ranged between 5-15%, with mesh complications accounting for 0.5% of patients overall. No mortality was reported after any procedures in a total of 1044 patients. Although inconsistently reported, good or satisfactory outcome occurred in 83% (74-91%) of patients; 86% (20-97%) of patients reported improvements in constipation after laparoscopic ventral mesh rectopexy (LVMR). About 2-7% of patients developed anatomical recurrence. Patient selection was inconsistently documented. As most common indication, high grade rectal intussusception was corrected in 80-100% of cases after robotic or LVMR. Healing of prolapse-associated solitary rectal ulcer syndrome occurred in around 80% of patients after LVMR.
Conclusion: Evidence supporting rectal suspension procedures is currently derived from poor quality studies. Methodologically robust trials are needed to inform future clinical decision making.