Elective Adhesiolysis vs. a Wait-and-see Policy to Prevent Recurrences After Conservative Treatment of Adhesive Small Bowel Obstruction (AWARE)

Rationale: Adhesive small bowel obstruction (aSBO) is a frequent surgical emergency, associated with 3-8% hospital mortality and a high risk of recurrence (20% at two years of follow-up). ASBO can be treated conservatively or by emergency surgery. In the absence of bowel ischemia or strangulation, conservative treatment is often preferred, to avoid the excess morbidity and mortality from emergency surgery. Recent epidemiological studies, however, demonstrate a considerable higher recurrence risk of aSBO after conservative treatment that is associated with hospital readmissions and lower survival. Elective adhesiolysis following successful conservative treatment might reduce these long-term risks whilst avoiding the high complication rate of emergency surgery.

Objective: The investigators aim to assess the efficacy of elective adhesiolysis following conservative treatment for aSBO as compared to the current state of the art (wait-and-see policy) to prevent long-term recurrence of aSBO. Further the investigators will evaluate quality of life, healthcare and societal costs.

Study design: Multicenter open-label randomized controlled trial, including 380 patients.

Study population: Adult patients who recovered from aSBO by conservative treatment. Patients that are inoperable for medical, anaesthesiological or surgical reasons are excluded. Intervention (if applicable): The intervention of investigation is elective adhesiolysis. Adhesiolysis is an abdominal procedure in which all adhesions are cut, and adhesion prevention applied to reduce the risk of adhesion reformation. The intervention is compared to wait-and-see policy (the current standard treatment)

Main study parameters/endpoints: Primary outcome is recurrence, defined as readmission for obstructive systems with aetiology of adhesions confirmed by CT. The investigators hypothesize a 50% reduction in recurrence in the intervention arm. Secondary outcomes are morbidity from surgery, health-related quality of life (EQ5D), healthcare costs and societal costs (iMCQ and iPCQ)

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

Patients in the intervention group are exposed to abdominal surgery, which is associated with a moderate risk of minor complications such as wound infection and haemorrhage, and a small risk of severe complications such as iatrogenic bowel injury. According to our hypothesis, a potential benefit is the reduction in the risk of recurrences. Recurrence of aSBO is associated with a risk of readmissions, reinterventions, and also increased long-term mortality.

Study Overview

• Status: Not yet recruiting
• Conditions: Adhesive Small Bowel Obstruction
• Intervention / Treatment: Procedure: Elective Adhesionlysis; Device: Adhesion barrier

• Study Type: Interventional
• Enrollment (Estimated): 380
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Richard PG ten Broek, MD, PhD; Phone Number: +31243611111; Email: richard.tenbroek@radboudumc.nl

Study Locations

• Belgium
  • Antwerpen, Belgium
    • UZ Antwerpen
    • Contact: Michiel de Maat, MD, PhD; Phone Number: +32 3 821 30 00; Email: michiel.demaat@uza.be
  • Brussels, Belgium
    • Hôpital Erasme
    • Contact: Nalja Bachir, MD, PhD; Phone Number: +32 2 555 31 11; Email: najla.bachir@hubruxelles.be
  • Brussles, Belgium
    • UZ Brussel
    • Contact: Jasper Stijns, MD, PhD; Phone Number: +32 2 477 41 11; Email: jasper.stijns@uzbrussel.be
  • Leuven, Belgium
    • UZ Leuven (National Coordinating Center)
    • Contact: Albert Wolthuis, Prof, MD, PhD; Phone Number: +32 16 33 22 11; Email: albert.wolthuis@uzleuven.be
  • Sint-Niklaas, Belgium
    • Vitaz Sint-Niklaas
    • Contact: Jean-Baptiste Cornille, MD, PhD; Phone Number: +323 760 60 60; Email: cornillejb@gmail.com
• Netherlands
  • Almelo, Netherlands
    • ZGT Almelo
    • Contact: Esther van den Ende, MD, PhD; Phone Number: +3188 708 7878; Email: e.vdende@zgt.nl
  • Amsterdam, Netherlands
    • OLVG Amsterdam
    • Contact: Steve de Castro, MD, PhD; Phone Number: +3120 599 9111; Email: s.m.m.decastro@olvg.nl
  • Boxmeer, Netherlands
    • Maasziekenhuis Pantein Boxmeer
    • Contact: Klaas Govaert, MD, PhD; Phone Number: +31485 845 000; Email: k.govaert@pantein.nl
  • Harderwijk, Netherlands
    • St. Jansdal Harderwijk
    • Contact: Caroline Andeweg, MD, PhD; Phone Number: +31 341 463 911; Email: cs.andeweg@stjansdal.nl
  • Maastricht, Netherlands
    • MaastrichtUMC+
    • Contact: Tim Lubbers, MD, PhD; Phone Number: +3143 387 6543; Email: tim.lubbers@mumc.nl
  • Nijmegen, Netherlands
    • Radboudumc
    • Contact: Richard PG ten Broek, MD, PhD; Phone Number: +31243611111; Email: richard.tenbroek@radboudumc.nl
  • Roermond, Netherlands
    • Laurentius Ziekenhuis Roermond
    • Contact: Jeroen Heemskerk, MD, PhD; Phone Number: +31475 382 222; Email: jeroen.heemskerk@LZR.nl
  • Rotterdam, Netherlands
    • St. Franciscus gasthuis Rotterdam
    • Contact: Eva Deerenberg, MD, PhD; Phone Number: +3110 461 6161; Email: e.deerenberg@franciscus.nl
  • Venlo, Netherlands
    • Vie Curie Venlo
    • Contact: Frits Aarts, MD, PhD; Phone Number: +3177 320 5555; Email: faarts@viecuri.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients aged 18 years and older who have recently recovered from aSBO by small bowel obstruction managed by conservative treatment.
• Patients who have previously been operated (high a prior risk of adhesions) are required to have no signs of other causes of bowel obstruction on imaging studies (CT-scan).
• Patients with no previous operation in history (low a prior risk of adhesions) are required to have typical signs for aSBO on imaging studies (abrupt change of bowel calibre, closed loop, or signs of torsion on vessels in the mesentery on CT-scan).

Exclusion Criteria:

• Patient who are unfit for reoperation for surgical, anesthesiological or medical reasons as determined by multidisciplinary team assessment or pre-operative screening
• Patients with active malignancy, reducing life expectancy
• Pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Elective Adhesiolysis; Elective adhesiolysis is a surgical procedure in which all adhesions in the abdomen are released. Elective adhesiolysis is preferably performed laparoscopy, but the precise surgical approach is adjusted to the expected location and extent of the adhesions based on factors including: presence of a stoma, abdominal wall defects, as well as the surgical history and locations of previous scarring.	Procedure: Elective Adhesionlysis; See descriptions in study arms; Device: Adhesion barrier; At the end of adhesiolysis a barrier will be placed. The adhesion barrier to be used in laparoscopic adhesiolysis is Icodextrin 4% (Adepttm).
No Intervention: Wait-and-see policy; A Wait-and-see policy is the current standard of care after a non-operatively treated epsiode of ASBO. No specific intervention or follow-up is performed in the control group of wait-and-see policy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
recurrence of ASBO at 2-years of follow-up	Recurrence is defined as a readmission for symptoms of small bowel obstruction, including lower abdominal pain, bloating and nausea with or without vomiting. In addition imaging by CT-scan should not show indications of other causes of bowel obstruction (such as an incarcerated abdominal wall hernia or tumour), which is over 90% accurate for the diagnosis of ASBO.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence at 5 year	(identified by record linking[BE] or general practitioner data[NL])	5 years
Recurrences needing surgery	ASBO recurrence requiring emergency surgery	2 years and 5 years
Morbidity from elective adhesiolysis	Composite of: Serious adverse events and complications, graded by Clavien-Dindo score.; Intra-operative events (i.e. bowel injury), graded by ClassIntra®; ICU admission; Reinterventions within 90 days	90 days
Health related quality of life	- Health-related quality of life measured by EQ5D	2 years
Gastro-intestinal related quality of life	- Gastro-intestinal related quality of life measured by GIQLI	2 years
Healthcare costs	measured by modified iMCQ	2 years
Societal costs	measured by modified iMCQ	2 years
Cost-effectiveness	incremental cost-effectiveness ratio, i.e. cost per QALY	2 years and 5 years

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Baxter Healthcare Corporation; ZonMw: The Netherlands Organisation for Health Research and Development; KCE Belgian Healthcare Knowledge Centre

Publications and helpful links

General Publications

• Krielen P, Kranenburg LPA, Stommel MWJ, Bouvy ND, Tanis PJ, Willemsen JJ, Migchelbrink J, de Ree R, Bormans EMG, van Goor H, Ten Broek RPG; ASBO Snapshot Study Group. Variation in the management of adhesive small bowel obstruction in the Netherlands: a prospective cross-sectional study. Int J Surg. 2023 Aug 1;109(8):2185-2195. doi: 10.1097/JS9.0000000000000471.
• van den Beukel BAW, Toneman MK, van Veelen F, van Oud-Alblas MB, van Dongen K, Stommel MWJ, van Goor H, Ten Broek RPG. Elective adhesiolysis for chronic abdominal pain reduces long-term risk of adhesive small bowel obstruction. World J Emerg Surg. 2023 Jan 23;18(1):8. doi: 10.1186/s13017-023-00477-9.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2034

Study Registration Dates

• First Submitted: December 30, 2024
• First Submitted That Met QC Criteria: January 10, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 10, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Surgery; Adhesiolysis; Tissue adhesions
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Recurrence; Intestinal Obstruction
• Other Study ID Numbers: NL88020.091.24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: At the end of the experiment and analyses, all data will be stored for 25 years in accordance with GCP regulations.
• IPD Sharing Access Criteria: Access to individual data will be made available upon reasonable request for academic purposes
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes