Transanal irrigation for the management of low anterior resection syndrome (LARS): protocol for a pragmatic, multicentre, crossover randomised controlled trial

Abstract

Introduction

Advances in surgical techniques and neoadjuvant care for rectal cancer have increased sphincter preservation, allowing restoration of bowel continuity through low anterior resection (LAR). However, up to 75% of patients experience low anterior resection syndrome (LARS), which is bowel dysfunction characterised by faecal incontinence, frequency, urgency and clustering of bowel movements, significantly impairing quality of life (QoL). Current management is largely empirical, using lifestyle or pharmacological strategies with variable success. Transanal irrigation (TAI) is a non-surgical intervention that allows controlled colonic washouts, improving symptom control. Evidence supporting TAI for LARS is limited by small sample sizes and is primarily observational, highlighting the need for a rigorous randomised controlled trial (RCT). This study aims to compare TAI with conventional LARS care on QoL, bowel function, faecal incontinence and satisfaction in adults with LARS following LAR.

Methods and analysis

This is a pragmatic, multicentre, crossover RCT conducted at eight academic hospitals across Quebec, Ontario and British Columbia, Canada. Eligible participants are adults (≥18 years) with an LARS score >20, at least 6 months post-LAR and without an ostomy or active colorectal complications. Participants will be randomised to receive either 3 months of daily TAI or conventional LARS care, followed by a 1 month washout and crossover to the alternate intervention. The TAI intervention includes an irrigation system, access to a web-based educational platform and virtual training with a research team member. Primary outcome is difference in global QoL between interventions, assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. Secondary outcomes include bowel function (LARS score), faecal incontinence (Cleveland Clinic Faecal Incontinence Score) and satisfaction. Sample size (n=66, accounting for 10% attrition) was determined using Monte Carlo simulations to detect a 6-point difference in QoL with 85.8% power. Data will be analysed using linear mixed-effects models accounting for period, treatment and sequence effects. All study data will be collected via Research Electronic Data Capture and maintained in secure, password-protected systems; participant confidentiality will be ensured throughout. Safety monitoring will include training on proper TAI technique and reporting of adverse events.

Ethics and dissemination

The study has received ethics approval from each participating site. The trial adheres to the Canadian Tri-Council Policy Statement on the use of human participants in research. Findings will be disseminated through peer-reviewed journals, conference presentations and scientific meetings, with authorship following the International Committee of Journal Editors guidelines.

Trial registration number

NCT05007015.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• Pragmatic crossover design allows within-subject comparisons, reducing variability and required sample size.

• Integration of a web-based educational platform enhances accessibility and standardisation of transanal irrigation training across multiple sites.

• Use of validated patient-reported outcome measures ensures robust assessment of quality of life, bowel function and faecal incontinence.

• Blinding of participants and outcome assessors is not feasible due to the nature of the intervention, which may introduce reporting bias.

Introduction

Advances in surgical techniques and neoadjuvant care for the treatment of rectal cancer have increased sphincter preservation rates, enabling restoration of bowel continuity following an oncological surgery, the low anterior resection (LAR). However, these advances are not without long-term functional consequences for patients.¹,³ Following LAR, 50–75% of patients experience some degree of bowel dysfunction, known as low anterior resection syndrome (LARS). This syndrome refers to a constellation of distressing and disruptive symptoms that include incontinence to stool and gas, frequency, urgency and clustering of bowel movements.⁴ It has been shown to significantly impair quality of life (QoL) and may persist indefinitely.^{2 3 5} With the rising incidence of rectal cancer in younger patients, LARS can have a particularly profound impact on patients’ ability to return to work and regain preoperative functional capacity.⁶,⁸

Due to the personal nature of each patient’s symptom cluster,⁹ the current management of LARS is empirical, guided by self-management using an ad hoc combination of lifestyle and pharmacological strategies, with mixed success.^{9 10} Several promising interventional strategies have been recently proposed for LARS, including pelvic physiotherapy, sacral neuromodulation and transanal irrigation (TAI).¹¹,¹⁴ Transanal irrigation has been proposed as a potential treatment for incontinence after anterior resections since 1989.¹⁵ It offers a non-surgical approach for managing LARS symptoms, allowing patients to perform controlled colonic washouts at scheduled times. Transanal irrigation systems introduce water into the rectum, facilitating bowel clearance through a combination of mechanical lavage and reflex-mediated stimulation of colonic peristalsis, thereby improving bowel emptying and symptom control.^{16 17}

The current evidence supporting TAI for the management of LARS remains limited, comprising primarily small-scale observational and interventional studies conducted in Europe¹⁸,²⁶ and Brazil.²⁷ A recent meta-analysis of these studies reported that TAI was both safe and effective in ameliorating LARS symptoms, particularly among patients with a prolonged disease course.²⁸ However, the authors cautioned that these findings should be interpreted carefully, as they predominantly reflect short-term outcomes derived from observational data.²⁸ Despite its limitations, the existing evidence on TAI for LARS collectively supports its potential efficacy and provides a strong rationale for a large-scale randomised controlled trial (RCT) in North America. Therefore, the aim of this pragmatic, multicentre, crossover RCT is to compare TAI with conventional LARS care (control, CON) in adults with LARS who have undergone LAR on QoL, bowel function, faecal incontinence and satisfaction. It is hypothesised that participants assigned to the TAI group will experience better QoL, bowel function, faecal incontinence and satisfaction compared with the ones assigned to the conventional LARS care group. To our knowledge, this study represents both the first North American-based trial and the largest RCT assessing TAI to date. Furthermore, it will be the first to deliver patient education, TAI training and support primarily through a virtual platform, thereby enhancing accessibility for individuals who do not reside near specialised colorectal centres.

Methods and analysis

Study design

This will be a pragmatic multicentre, crossover RCT conducted from January 2022 to January 2027 across the following eight academic hospitals in the Canadian provinces of Quebec, Ontario and British Columbia:

• Quebec:

  • Jewish General Hospital (JGH), Montreal.

  • McGill University Health Centre - Montreal General Hospital, Montreal.

  • Centre de recherche du CHU de Québec - Hôpital Saint-François d’Assise, Quebec City.

• Ontario:

  • University Health Network, Toronto.

  • Health Sciences North, Sudbury.

  • London Health Sciences Centre, London.

• British Columbia:

  • Providence Health Care - St. Paul’s Hospital, Vancouver.

  • University of British Columbia - Island Health Colorectal Surgery, Victoria.

The corresponding research protocol fulfils the requirements of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist²⁹ (online supplemental appendix 1).

Outcome measures

The primary outcome is as follows:

• Difference in global QoL between the TAI and CON interventions.

The secondary outcomes are as follows:

• Difference in bowel function between the TAI and CON interventions.

• Difference in faecal incontinence between the TAI and CON interventions.

• Difference in satisfaction between the TAI and CON interventions.

Research participants

Participants will be eligible for recruitment if they meet all of the following inclusion criteria: adults (≥18 years) with an LARS score >20, who have undergone LAR by laparoscopic, robotic, transanal total mesorectal excision or open approach, with or without creation of a diverting loop ileostomy for the treatment of rectal cancer, advanced adenoma or dysplasia and who have had their ileostomy closed (if applicable) at least 6 months prior to study enrolment.

Exclusion criteria include:

• Inability to provide informed consent, including insufficient fluency in English or French.

• Inability to access the internet.

• Presence of an ostomy at the time of study enrolment.

• Active or ongoing treatment for rectal disease.

• Anastomotic stricture, sinus or any other ongoing anastomotic complication.

• Current use of TAI under the direction of a clinical team.

Recruitment strategy, enrolment and randomisation

Potential participants will be approached by their colorectal surgeon at one of the designated hospitals during a routine postoperative and/or surveillance visit, occurring at least 6 months after completion of rectal cancer treatment. Participants may also be identified among patients referred to a participating colorectal centre for LARS management. The site research coordinator will subsequently contact eligible participants to provide detailed information regarding the study and to obtain written informed consent (online supplemental appendix 2). Following confirmation of eligibility and enrolment, participants will be randomised using a stratified, blocked randomisation design with computer-generated, permuted blocks of randomly varying sizes (four or six). Randomisation will be stratified by hospital sites to account for potential site-specific differences. An online centralised randomisation system will be employed to maintain allocation concealment. The lead study coordinator will be responsible for both enrolling participants and assigning them to the intervention groups. Blinding of participants and outcome assessors is not feasible due to the nature of the intervention.

Experimental protocol

An outline of the experimental protocol is given in figure 1, and the schedule of enrolment, interventions and assessments are provided in figure 2. Following randomisation, participants will receive an onboarding email and a subsequent call from a study coordinator to review study assessments, interventions and the trial timeline. The onboarding email will provide participants with credentials (username and password) for a web-based educational platform (https://www.larsapp.ca/) and an individualised schedule outlining all planned assessments and interventions (online supplemental appendix 3).

Figure 1. Experimental protocol. CON, conventional low anterior resection syndrome care arm; QoL, quality of life; TAI, transanal irrigation arm.

Figure 2. SPIRIT 2025 diagram of the schedule of enrolment, interventions and assessments. CON, conventional low anterior resection syndrome care arm; SPIRIT, Standard Protocol Items: Recommendations for Interventional Trials; QoL, quality of life; TAI, transanal irrigation arm.

Patient-reported outcome measures (PROMs, ie, global QoL, bowel function and faecal incontinence) and a satisfaction questionnaire (online supplemental appendix 4) will be collected before the start and at the end of each 3-month intervention period (ie, TAI and CON), which is separated by a 1-month washout phase. A 2-week bowel diary will be completed daily during the final 2 weeks of each arm (CON and TAI) as well as the final 2 weeks of the washout period via the platform (online supplemental appendix 5). Additionally, an irrigation diary will be completed daily during the TAI intervention period using the same platform (online supplemental file 6).

Intervention and study discontinuation

Transanal irrigation arm

Participants randomised to the TAI intervention arm will undergo a 3-month intervention consisting of daily TAI while continuing conservative management, as per usual care provided by the treating healthcare team. On randomisation, participants will receive a mailed package containing the irrigation device (Coloplast Peristeen anal irrigation system) and instructional materials, as well as access to a web-based educational platform (https://www.larsapp.ca/). The platform, developed with input from a multidisciplinary team, provides educational content to support rectal cancer survivors with LARS, promotes self-management and enhances patient engagement and well-being.^{30 31} For this study, the application has been modified for TAI-specific use: peer-support tools have been removed, and content now includes videos and written instructions on performing TAI, patient testimonials and a portal for submitting questionnaires to the study team. It is accessible on any internet-enabled device.

Within the first 2 weeks following randomisation, participants will have a virtual training session with a trained research team member. This one-on-one session will review the instructional materials, demonstrate device use and address participants’ questions. Additional support sessions (by phone or in-person) can be scheduled as needed.

Participants will perform daily irrigation using a single-use catheter connected to the irrigation system, prefilled with tap water. An initial irrigation volume of 1000 mL is recommended, which may be adjusted between 500 and 1500 mL according to participants’ tolerance. Catheters are to be disposed of after each use as per manufacturer directions, while the reusable irrigation device is provided for the full 3-month intervention period. Participants will be instructed to irrigate daily or every 1–2 days, following manufacturer guidelines to discard the system after 90 uses. Each session is expected to take approximately 20–90 min, depending on individual tolerance. Participants may adjust the frequency of irrigation based on preference or tolerance; such modifications will not be considered protocol deviations, unless irrigation is discontinued entirely. During the intervention period, an irrigation diary will be completed daily using the web-based educational platform (online supplemental appendix 6).

Conventional LARS care arm

During the control phase, participants will receive an educational LARS booklet previously developed by our research group³² and usual LARS care of their respective hospital. Participants will be expected to continue any previously prescribed management strategies or medications for LARS.

Washout period

A 1-month washout period will be implemented between intervention arms. Minimal contamination between study phases is expected, as the effects of the intervention are limited to the period during which irrigations are performed. Participants will receive the irrigation materials for the 3-month intervention period and no additional materials will be provided to continue the irrigation by the study team. This approach is expected to minimise the risk of participants continuing irrigation during the CON phase.

Study discontinuation

Participants initially randomised to the TAI intervention arm who feel they are benefiting from the treatment and are unwilling to discontinue irrigation during the control phase may exit the study. Those wishing to continue irrigation will be asked to continue documenting their experience through the planned PROMs. All withdrawals, including reasons for withdrawal, will be reported.

Baseline data, PROMs and questionnaires

Baseline demographics, medical comorbidities, disease-related and treatment-related characteristics will be obtained through hospital chart review, including known predictors of poor bowel function such as tumour height, neoadjuvant radiotherapy, reconstruction technique and history of previous anastomotic leak.

The following PROMs will be assessed before the beginning and at the end of each intervention arm:

• Global QoL: Assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30).³³

• Bowel function: Assessed using the LARS score.⁴

• Faecal incontinence: Assessed using Cleveland Clinic Faecal Incontinence Score.³⁴

In addition to the PROMs, participants will complete a satisfaction questionnaire before the start and at the end of each 3-month intervention period. Lastly, a 2-week bowel diary will be completed daily at baseline and during the final 2 weeks of each arm (CON and TAI) as well as the final 2 weeks of the washout period (online supplemental appendix 5).

Statistical analysis

Sample size estimate

Monte Carlo simulations were performed to estimate statistical power. These simulations required specification of the fixed effects (baseline and period effects) and the variability of the data (SDs for both the random effect and the residual error). Parameter estimates were obtained from the literature: a baseline QoL (intercept) of 65, a period effect of 5 points, an SD for the random effect of 5 and an SD for the error term of 10.^{2 3 35} Using these parameters, 1000 datasets were simulated with a total sample size of 60 patients (6 sites×10 patients per site). The simulations indicated that the study would be able to detect a 6-point difference in QoL with 85.8% power (95% CI 83.48 to 87.91). According to consensus guidelines for the EORTC-QLQ-C30, a 10-point difference in global QoL is considered clinically meaningful for interventions targeting cancer-related QoL.^{3 36} Therefore, a planned sample size of 60 patients is expected to provide adequate precision. To account for an anticipated 10% attrition rate, the final adjusted sample size is 66 patients.

Data analysis

Descriptive statistics will be reported as mean (SD) or median (IQR) for continuous variables and counts (percentages) for categorical variables. Analyses will follow the intention-to-treat principle, with a complementary per-protocol analysis excluding participants who withdraw or cross over before completing the assigned intervention. Continuous outcomes (eg, global QoL) will be analysed using linear mixed-effects models with treatment (TAI vs CON), period (first vs second phase) and sequence (TAI followed by CON vs CON followed by TAI) as fixed effects and a subject-specific random intercept; carryover will be evaluated via a treatment-by-sequence interaction, and if significant, only first-period data will be analysed using a parallel-group framework. Count outcomes (eg, bowel frequency) will be modelled using mixed-effects Poisson regression with overdispersion assessed; if present, a negative binomial model will be used and zero-inflated variants will be considered if appropriate. Binary outcomes will be analysed using mixed-effects logistic regression with the same fixed and random effects structure. Ordinal outcomes (eg, LARS categories and Likert-type satisfaction) will be analysed using cumulative logit mixed-effects models; the proportional-odds assumption will be checked, with partial proportional-odds or multinomial mixed models used if violated. Model assumptions will be assessed using residual diagnostics and goodness-of-fit; transformations or non-parametric alternatives will be applied as needed. Missing data will be assessed for its mechanism. If less than 5%, a complete-case analysis will be performed; if 5% or more, or if patterns indicate data are missing at random, multiple imputation by chained equations will be applied, with sensitivity analyses comparing imputed and non-imputed results. Two-sided tests will use α=0.05. No interim analyses are planned given the trial’s duration and risk profile. Analyses will be conducted in R V.4.5.2 (R Foundation for Statistical Computing, Vienna, Austria), with relevant packages including lme4, glmmTMB, ordinal and mice.

Data management

Before participating in the study, all participants will be informed of the procedures and potential risks involved in the investigation and will be asked to provide written informed consent. Moreover, participants will be informed that all data collected during the study will be kept private, and no personal identifiable information will be shared. Participant confidentiality will be maintained in accordance with the Charter of Rights and Freedoms, the Civil Code of Quebec and other relevant provincial legislation. On enrolment, participants will be assigned a unique study identification number and the key linking participant identities to study data will be stored in a password-protected Excel file, accessible only to the principal investigators. For the purposes of TAI training, participants’ identities will necessarily be known to the research team conducting the intervention, while all other study personnel will access only de-identified data.

Study data will be collected and managed using Research Electronic Data Capture (REDCap),³⁷ a secure, web-based electronic data capture platform hosted and maintained by the female Davis Institute at the JGH. Participants who prefer to complete PROMs on paper will be mailed physical copies to complete and return to the lead study team. Electronic data will be stored on a password-protected JGH server, and paper forms will be secured in locked cabinets at the study site, accessible only to authorised research personnel. Each participant will be assigned a unique code number through REDCap, and all study data will be identified using this code to protect participant confidentiality. A separate document linking codes to participant identities will be stored on a password-protected computer on the JGH secure institutional server and will be accessible only to authorised members of the research team. Personal information will be maintained in separate, password-protected files on the same secure server.

In accordance with institutional policy, study data will be retained for 25 years. After 10 years, all data will be anonymised for indefinite storage, and consent forms will be securely shredded using the confidential disposal services provided by the CIUSSS du Centre-Ouest-de-l’Île-de-Montréal. A notification will also be provided to the Research Ethics Board (REB) certifying completion of secure data destruction. If participants decide to discontinue the study, no other information will be collected; however, the data already collected will be kept, unless participants specifically request that it be destroyed. Only the study team will have access to all hard copy and electronic datasets.

Data monitoring and safety

No formal data monitoring committee has been established for this study. Given the short duration of the trial, no interim analyses are planned. The study team will perform regular audits of the collected data to ensure that PROMs are being completed according to protocol; however, no independent audit is planned.

Rectal irrigation via enemas is routinely used during oncological surveillance following an LAR. In this study, however, the intervention involves daily irrigation with larger volumes, which carries a small risk of local trauma or, in rare cases, rectal perforation. No such complications have been reported in patients with LARS in the current literature.¹⁵²³,25 27 35 38 Any perforation would be reported immediately as a serious adverse event to the JGH REB. Risk mitigation includes comprehensive participant training on proper technique and selection of a lower-risk population (patients at least 6 months post-surgery). Other potential adverse effects, which will be disclosed to participants, include minor bleeding, abdominal pain, nausea and discomfort during device insertion. These events are typically transient and resolve on discontinuation of treatment.

The irrigation device (Coloplast Peristeen anal irrigation system) was originally designed for faecal incontinence. Its use in patients with LARS has been demonstrated in other studies; however, manufacturer instructions recommend special caution in patients with prior anal or colorectal surgery.²³,²⁵⁴³ In this study, TAI will be performed under medical supervision to ensure patient safety, particularly because alternative treatment options may carry higher risk. Large-scale audits indicate that TAI is a safe procedure, with bowel perforation rates estimated at 2–6 per million procedures.⁴⁴ Nonetheless, the intervention should always be introduced with experienced healthcare personnel to provide appropriate guidance.

The irrigation procedure requires time commitment from participants. The duration of each session varies, with a reported mean of approximately 45 min (range 20–90 min).^{27 39} This time investment is expected to be offset by overall reductions in bowel movements and time spent managing LARS symptoms during the rest of the day.

Any incidental findings identified during the study will be disclosed directly to the participant by the principal investigator. With the participant’s consent, these findings will also be communicated to their primary care physician or relevant surgeon for follow-up outside the trial.

Patient and public involvement

Patients were involved from the inception of the research. The study originated from patient-identified priorities, as patients brought TAI to the attention of the research team as a management strategy of interest, which directly informed the development of the research question and overall study design. Five patient partners contributed to the design and conduct of the study, including the development, review and refinement of patient-facing study materials. Patient partners emphasised the importance of QoL as a primary outcome rather than bowel function alone, which informed the selection of the primary outcome measure. Patient partners also supported study recruitment by sharing information through patient networks, including social media platforms (eg, an LARS Facebook group) and by word-of-mouth. Patients will be involved in the interpretation of study findings and in agreeing dissemination plans, with results to be shared through social media, colorectal cancer support groups and patient communities.

Ethics and dissemination

The research protocol was approved by the REB of each location involved:

• Quebec:

  • JGH, Montreal:

    • REB: JGH REB.

    • Study ID: MP-05-2022-2925.

  • McGill University Health Centre - Montreal General Hospital, Montreal:

    • REB: McGill University Health Centre REB.

    • Study ID: MEO-05-2022-7970.

  • Centre de recherche du CHU de Québec - Hôpital Saint-François d’Assise, Quebec City:

    • REB: Comité d’éthique de la recherche/CHU de Québec-Université Laval.

    • Study ID: MEO-05-2023-6410.

• Ontario:

  • University Health Network, Toronto:

    • REB: University Health Network REB.

    • Study ID: 22–5339.0 IRRIGANT 1.

  • Health Sciences North, Sudbury:

    • REB: Health Sciences North REB.

    • Study ID: 23–015.

  • London Health Sciences Centre, London:

    • REB: Western’s Health Sciences REB.

    • Study ID: 121964.

• British Columbia:

  • University of British Columbia - Island Health Colorectal Surgery, Victoria:

    • REB: Clinical REB, Vancouver Island Health Authority.

    • Study ID: H22-01977-A004.

  • Providence Health Care - St. Paul’s Hospital, Vancouver:

    • REB: Providence Health Care REB.

    • Study ID: H22-01977.

If important protocol modifications are needed, the research team will contact each REB, trial registry (ClinicalTrials.gov) and trial participants. This study complies with the standards as set out in the Canadian Tri-Council Policy statement on the use of human participants in research.

The results of this study will be disseminated to researchers, health professionals and the general public by publication in peer-reviewed national and international journals, as well as by poster and oral presentations at medical and surgical conferences and scientific meetings. Authorship will follow the recommendations of the International Committee of Journal Editors.