Stepped-wedge randomized controlled trial of laparoscopic ventral mesh rectopexy in adults with chronic constipation

Abstract

Background The effectiveness of laparoscopic ventral mesh rectopexy (LVMR) in patients with defecatory disorders secondary to internal rectal prolapse is poorly evidenced. A UK-based multicenter randomized controlled trial was designed to determine the clinical efficacy of LVMR compared to controls at medium-term follow-up. Methods The randomized controlled trial was conducted from March 1, 2015 TO January 31, 2019. A stepped-wedge RCT design permitted observer-masked data comparisons between patients awaiting LVMR (controls) with those who had undergone surgery. Adult participants with radiologically confirmed IRP refractory to conservative treatment were randomized to three arms with different delays before surgery. Efficacy outcome data were collected at equally stepped time points (12, 24, 36, 48, 60, and 72 weeks). Clinical efficacy of LVMR compared to controls was defined as ≥ 1.0-point reduction in Patient Assessment of Constipation-Quality of Life and/or Symptoms (PAC-QOL and/or PAC-SYM) scores at 24 weeks. Secondary outcome measures included 14-day diary data, the Generalized Anxiety Disorder scale (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), St Marks incontinence score, the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), the chronic constipation Behavioral Response to Illness Questionnaire (CC-BRQ), and the Brief Illness Perception Questionnaire (BIPQ). Results Of a calculated sample size of 114, only 28 patients (100% female) were randomized from 6 institutions (due mainly to national pause on mesh-related surgery). Nine were assigned to the T0 arm, 10 to T12, and 9 to T24. There were no substantial differences in baseline characteristics between the three arms. Compared to baseline, significant reduction (improvement) in PAC-QOL and PAC-SYM scores were observed at 24 weeks post-surgery (– 1.09 [95% CI – 1.76, – 0.41], p = 0.0019, and – 0.92 [– 1.52, – 0.32], p = 0.0029, respectively) in the 19 patients available for analysis (9 were excluded for dropout [n = 2] or missing primary outcome [n = 7]). There was a clinically significant long-term reduction in PAC-QOL scores (− 1.38 [− 2.94, 0.19], p = 0.0840 at 72 weeks). Statistically significant improvements in PAC-SYM scores persisted to 72 weeks (− 1.51 [− 2.87, − 0.16], p = 0.0289). Compared to baseline, no differences were found in secondary outcomes, except for significant improvements at 24 and 48 weeks on CC-BRQ avoidance behavior (− 14.3 [95% CI − 23.3, − 5.4], and − 0.92 [− 1.52, − 0.32], respectively), CC-BRQ safety behavior (− 13.7 [95% CI − 20.5, − 7.0], and − 13.0 [− 19.8, − 6.1], respectively), and BIPQ negative perceptions (− 16.3 [95% CI − 23.5, − 9.0], and − 10.5 [− 17.9, − 3.2], respectively). Conclusions With the caveat of under-powering due to poor recruitment, the study presents the first randomized trial evidence of short-term benefit of LVMR for internal rectal prolapse. Trial registration ISRCTN Registry (ISRCTN11747152).

Sample Size Calculation for an Individual Stepped‐Wedge Randomized Trial

“…Although appealing, this design has not been widely used. It has been used in studies of obstructive sleep apnea (Truby et al 2019), chronic constipation (Grossi et al 2022), fine particulate matter exposure (Benka-Coker et al 2021), juvenile idiopathic arthritis (Ilowite et al 2014), myositis (Aggarwal et al 2016;Oddis et al 2013), or even vascular malformations (ClinicalTrials.gov, 2019;Maruani et al 2021). However, its use is reviewed among multiple designs addressing challenges in small clinical trials (Allemang-Trivalle et al 2023;Cornu et al 2013) to study rare disorders (Abrahamyan et al 2016) or studies of fragile populations such as children (Balevic While several publications focused on the analysis of ISW-RTs 2 designs, none, to our knowledge, proposed a sample size derivation.…”

“…2019), chronic constipation (Grossi et al. 2022), fine particulate matter exposure (Benka‐Coker et al. 2021), juvenile idiopathic arthritis (Ilowite et al.…”