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

NCT02961582 | Completed DMC

• 1 other identifier: NL57367.068.16
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Constipation; Surgery

Keywords

Sacral neuromodulation; Constipation; Slow-transit constipation; Surgery; Colorectal surgery; Cost-effectiveness; Quality of life

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Defecation frequency

  1 and 3 months

• Proportion of patients with a 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

  Baseline, 1, 3 and 6 months

• Constipation severity

  Baseline, 1, 3 and 6 months

• Fatigue

  Baseline, 1, 3 and 6 months

Study Arms (2)

Sacral Neuromodulation

EXPERIMENTAL

Device: Sacral Neuromodulation

Personalized Conservative Treatment

OTHER

Other: Personalized Conservative Treatment

Interventions

Sacral Neuromodulation DEVICE

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.

Also known as: Medtronic Interstim Therapy System

Sacral Neuromodulation

Personalized Conservative Treatment OTHER

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.

Also known as: Care as usual

Personalized Conservative Treatment

Eligibility Criteria

• Age: 14 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Dutch National Health Care Institute: collaborator
• Medtronic: collaborator

Study Sites (2)

Maastricht University Medical Centre

Maastricht, Limburg, 6229 HX, Netherlands

Location

Groene Hart Ziekenhuis

Gouda, South Holland, 2800 BB, Netherlands

Location

Related Publications (5)

• Mugie SM, Benninga MA, Di Lorenzo C. Epidemiology of constipation in children and adults: a systematic review. Best Pract Res Clin Gastroenterol. 2011 Feb;25(1):3-18. doi: 10.1016/j.bpg.2010.12.010.

  PMID: 21382575 BACKGROUND

• Suares NC, Ford AC. Prevalence of, and risk factors for, chronic idiopathic constipation in the community: systematic review and meta-analysis. Am J Gastroenterol. 2011 Sep;106(9):1582-91; quiz 1581, 1592. doi: 10.1038/ajg.2011.164. Epub 2011 May 24.

  PMID: 21606976 BACKGROUND

• van Wunnik BP, Peeters B, Govaert B, Nieman FH, Benninga MA, Baeten CG. Sacral neuromodulation therapy: a promising treatment for adolescents with refractory functional constipation. Dis Colon Rectum. 2012 Mar;55(3):278-85. doi: 10.1097/DCR.0b013e3182405c61.

  PMID: 22469794 BACKGROUND

• Heemskerk SCM, Rotteveel AH, Benninga MA, Baeten CIM, Masclee AAM, Melenhorst J, van Kuijk SMJ, Dirksen CD, Breukink SO. Sacral neuromodulation versus personalized conservative treatment in patients with idiopathic slow-transit constipation: study protocol of the No.2-trial, a multicenter open-label randomized controlled trial and cost-effectiveness analysis. Int J Colorectal Dis. 2018 Apr;33(4):493-501. doi: 10.1007/s00384-018-2978-x. Epub 2018 Feb 22.

  PMID: 29470731 BACKGROUND

• Heemskerk SCM, Dirksen CD, van Kuijk SMJ, Benninga MA, Baeten CIM, Masclee AAM, Melenhorst J, Breukink SO. Sacral Neuromodulation Versus Conservative Treatment for Refractory Idiopathic Slow-transit Constipation: The Randomized Clinical No.2-Trial. Ann Surg. 2024 May 1;279(5):746-754. doi: 10.1097/SLA.0000000000006158. Epub 2023 Nov 23.

  PMID: 37991178 DERIVED

MeSH Terms

Conditions

Constipation

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Stéphanie O Breukink, Dr.

  Maastricht University Medical Centre+

  PRINCIPAL INVESTIGATOR

• Carmen D Dirksen, Prof. dr.

  Maastricht University Medical Centre+

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2016
• First Posted: November 11, 2016
• Study Start: February 21, 2017
• Primary Completion: July 31, 2021
• Study Completion: December 31, 2021
• Last Updated: June 13, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2)