Effectiveness and Safety 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. Study design: A prospective cohort study with one group. This study is conducted next to a randomized controlled clinical trial (RCT) on 'the effectiveness and cost-effectiveness of sacral neuromodulation in patients with idiopathic slow-transit constipation refractory to conservative treatments' (for more information ClinicalTrial.gov ID: NCT02961582). This RCT is part of a temporary reimbursement arrangement, called conditional reimbursement of health care (in Dutch: Voorwaardelijke Toelating) of the National Health Care Institute (Zorginstituut Nederland). As part of this arrangement, the Ministry of Health, Welfare and Sports requires that SNM remains available for eligible patients during the conditional reimbursement period, also when inclusion of the RCT has ended. Furthermore, the Ministry requires that patients who received personalized conservative treatment in the RCT (control group), are offered SNM after completion of their follow-up of 6 months. As a result, the National Health Care Institute requires that the patients who receive SNM outside the RCT are included in a prospective cohort study to be able to collect data on them. Aim: The aim of this prospective cohort study is to collect more (but uncontrolled) information regarding the safety and effectiveness of SNM. 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, the pacemaker will be removed and patients receive conservative treatment. Main study parameters/endpoints: The primary outcome is treatment success at 6 months, defined as an average DF of ≥3 a week according to a 3-week defecation diary and safety. Secondary outcomes are straining, sense of incomplete evacuation, constipation severity and generic (health-related) quality of life ((HR)QOL).

Official Title
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Effectiveness and Safety 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


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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sacral Neuromodulation (SNM)<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 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;|

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 | 
| Complications/adverse events | Reported by the clinician in a case report form (CRF) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. In patients who still have the pacemaker at 6 months, outcomes are als measured 12 months after inclusion to monitor the longer term effectiveness and safety of SNM. | Baseline, 1, 3 and 6 months, (12 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. In patients who still have the pacemaker at 6 months, outcomes are als measured 12 months after inclusion to monitor the longer term effectiveness and safety of SNM. | Baseline, 1, 3 and 6 months, (12 months) | 
| Constipation severity | Displayed with the score from the Wexner constipation score (WCS). In patients who still have the pacemaker at 6 months, outcomes are als measured 12 months after inclusion to monitor the longer term effectiveness and safety of SNM. | Baseline, 1, 3 and 6 months, (12 months) | 
| Generic (HR)QOL | Displayed with the score from the EQ-5D-5L. In patients who still have the pacemaker at 6 months, outcomes are als measured 12 months after inclusion to monitor the longer term effectiveness and safety of SNM. | Baseline, 1, 3 and 6 months, (12 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