Clinical trial NCT02961582: Effectiveness and Cost-effectiveness of Sacral Neuromodulation in Patients With Idiopathic Slow-transit Constipation
Official title: Effectiveness and Cost-effectiveness of Sacral Neuromodulation in Patients With Idiopathic Slow-transit Constipation Refractory to Conservative Treatments
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Constipation
Surgery
Keywords: Sacral neuromodulation
Constipation
Slow-transit constipation
Surgery
Colorectal surgery
Cost-effectiveness
Quality of life
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Dutch National Health Care Institute
name: Medtronic
First posted: 2016-11-11
Enrollment: 67
Sex: ALL
Minimum age (years): 14
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Treatment success at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Defecation frequency
timeFrame: 1 and 3 months
measure: Proportion of patients with a 50% reduction in the proportion of defecations with straining
timeFrame: Baseline, 1, 3 and 6 months
measure: Proportion of patients with a 50% reduction in the proportion of defecations with a sense of incomplete evacuation
timeFrame: Baseline, 1, 3 and 6 months
measure: Constipation severity
timeFrame: Baseline, 1, 3 and 6 months
measure: Fatigue
timeFrame: Baseline, 1, 3 and 6 months
measure: Constipation-specific (health-related) quality of life ((HR)QOL)
timeFrame: Baseline, 1, 3 and 6 months
measure: Generic (HR)QOL
timeFrame: Baseline, 1, 3 and 6 months
measure: Adverse events/complications
timeFrame: Baseline, 1, 3 and 6 months
measure: Resource use/costs
timeFrame: Baseline, 3 and 6 months
measure: Cost-effectiveness
timeFrame: 6 months
measure: Budget-impact
timeFrame: 6 months
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre
state: Limburg
city: Gouda
country: Netherlands
facility: Groene Hart Ziekenhuis
state: Zuid-Holland
Study officials:
affiliation: Maastricht University Medical Centre+
name: Stéphanie O Breukink, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Maastricht University Medical Centre+
name: Carmen D Dirksen, Prof. dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.