Effectiveness and Cost-effectiveness of Sacral Neuromodulation in Patients With Idiopathic Slow-transit Constipation

Study Overview
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Brief Summary
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Rationale: Previous reviews showed that the evidence regarding the effectiveness of sacral neuromodulation (SNM) in patients with therapy-resistant, idiopathic (slow-transit) constipation is of suboptimal quality. Furthermore, there is no estimate of costs and cost-effectiveness in this patient group. Objective: The main objective of this study is to assess the effectiveness of SNM compared to personalized conservative treatment (PCT), in patients with idiopathic slow-transit constipation who are refractory to conservative treatment. The secondary objectives are assessing the 1) costs, 2) cost-effectiveness and 3) budget-impact of SNM compared to PCT. Hypothesis: Based on previous research we hypothesize that SNM will be more effective than PCT in terms of a significantly higher proportion of patients having treatment success at 6 months. Study design: An open-label pragmatic randomized controlled trial (RCT) combined with a prospective cohort study. Study population: Adolescent (14-17 years) and adult (18-80 years) patients with idiopathic slow-transit constipation refractory to conservative treatment. Intervention: The intervention is SNM, a minimally invasive surgical procedure consisting of two phases. In the screening phase an electrode is inserted near the third sacral nerve and connected to an external stimulator. If the screening phase is successful (average defecation frequency (DF) ≥3 a week), the electrode is connected to a pacemaker that is implanted in the buttocks of the patient. If not successful, patients receive conservative treatment. The control intervention is PCT. This is the best and least invasive alternative to SNM. PCT consists of medication and/or retrograde colonic irrigation. Main study parameters/endpoints: The primary outcome is success at 6 months, defined as an average DF of ≥3 a week according to a 3-week defecation diary. Secondary outcomes are straining, sense of incomplete evacuation, constipation severity, fatigue, constipation specific and generic (health-related) quality of life ((HR)QOL), and costs at 6 months. Furthermore, cost-effectiveness and budget-impact will be estimated.

Official Title
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Effectiveness and Cost-effectiveness of Sacral Neuromodulation in Patients With Idiopathic Slow-transit Constipation Refractory to Conservative Treatments

Conditions
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Constipation, Surgery

Intervention / Treatment
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* Device: Sacral Neuromodulation
* Other: Personalized Conservative Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: An average defecation frequency (DF) of <3 per week based on a 3-week defecation diary (patient-reported) Meet at least one other criterion of the Rome-IV criteria for idiopathic constipation based on the 3-week defecation diary (1) Refractory to conservative treatment Age: 14-80 years Slow-transit constipation (1) Rome-IV criteria for idiopathic constipation: Straining during ≥25% of defecations Lumpy or hard stools in ≥25% of defecations Sensation of incomplete evacuation for ≥25% of defecations Sensation of anorectal obstruction/blockage for ≥25% of defecations Manual manoeuvres to facilitate ≥25% of defecations Exclusion Criteria: Obstructed outlet syndrome (objectified by defeacography) Irritable bowel syndrome (Rome-IV criteria for irritable bowel syndrome) Congenital or organic bowel pathology Rectal prolapse Anatomical limitations preventing placement of an electrode Skin and perineal disease with risk of infection Previous large bowel/rectal surgery Stoma Coexisting neurological disease Significant psychological co-morbidity as assessed subjectively by the investigator Being or attempting to become pregnant during study follow-up

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sacral Neuromodulation<br> | Device: Sacral Neuromodulation<br>* SNM starts with a screening phase. In this phase a tined lead is inserted into the third sacral foramen and attached to an external stimulator, after which the patient enters a four-week stimulation test period. If the screening phase is successful (defecation frequency (DF) ≥3 a week), the external stimulator is changed for a pacemaker that is implanted in the buttocks. If the screening phase is unsuccessful (DF <3 a week), the lead is explanted. Patients in the intervention group are asked to limit the use of additional conservative treatments for constipation (such as laxatives and colonic irrigation) to what is necessary to relieve (the most severe) complaints. What is necessary to relieve complaints is determined by the patient.<br>* Other names: Medtronic Interstim Therapy System;|
| Other: Personalized Conservative Treatment<br> | Other: Personalized Conservative Treatment<br>* The control group will receive the best and least invasive alternative treatment, which is personalized conservative treatment (PCT). PCT includes, a combination of laxative/medication use and/or colonic irrigation, depending on the preferences of the patient. Use of PCT will be documented.<br>* Other names: Care as usual;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment success at 6 months | Treatment success is defined as an average defecation frequency of ≥ 3 a week based on a patient-reported defecation diary over a period of 3 weeks | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Defecation frequency | Defecation frequency based on a patient-reported defecation diary over a period of 3 weeks | 1 and 3 months | 
| Proportion of patients with a 50% reduction in the proportion of defecations with straining | The proportion of defecations with straining is derived from the data in the 3 week defecation diary. The reported proportion of defecations with straining is compared with the proportion of defecations with straining at baseline. Patients are divided in two groups: 1) ≥50% reduction in the proportion of defecations with straining and 2) <50% reduction in the proportion of defecations with straining. | Baseline, 1, 3 and 6 months | 
| Proportion of patients with a 50% reduction in the proportion of defecations with a sense of incomplete evacuation | The proportion of defecations with a sense of incomplete evacuation is derived from the data in the 3 week defecation diary. The reported proportion of defecations with a sense of incomplete evacuation is compared with the proportion of defecations with a sense of incomplete evacuation at baseline. Patients are divided in two groups: 1) ≥50% reduction in the proportion of defecations with a sense of incomplete evacuation and 2) <50% reduction in the proportion of defecations with a sense of incomplete evacuation. | Baseline, 1, 3 and 6 months | 
| Constipation severity | Displayed with the score from the Wexner constipation score (WCS). | Baseline, 1, 3 and 6 months | 
| Fatigue | Displayed with the score from the Fatigue Questionnaire (in Dutch 'Verkorte vermoeidheidsvragenlijst' (VVV)) . | Baseline, 1, 3 and 6 months | 
| Constipation-specific (health-related) quality of life ((HR)QOL) | Displayed with the score from the Patient Assessment of Constipation - Quality of Life (PAC-QOL) questionnaire | Baseline, 1, 3 and 6 months | 
| Generic (HR)QOL | In adults displayed with the score from the EQ-5D-5L and ICECAP-A In adolescents displayed with the score from the EQ-5D-5L and KIDSCREEN-27 | Baseline, 1, 3 and 6 months | 
| Adverse events/complications | Reported by the clinician in a case report form (CRF) | Baseline, 1, 3 and 6 months | 
| Resource use/costs | Health care costs, patient and family costs and costs outside the health care sector | Baseline, 3 and 6 months | 
| Cost-effectiveness | Both from a societal and health care perspective, derived from the EQ-5D-5L scores and cost data obtained in this RCT | 6 months | 
| Budget-impact | From a societal, health care and health care insurance perspective, derived from the EQ-5D-5L scores and cost data obtained in this RCT | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sacral neuromodulation, Constipation, Slow-transit constipation, Surgery, Colorectal surgery, Cost-effectiveness, Quality of life