COlonic Salvage by Therapeutic Appendectomy.

NCT03912714 | Completed

• 1 other identifier: 2018_058
• Study Type: interventional
• Target: 123
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: The annual incidence of ulcerative colitis (UC) amounts to 6-8 new cases per 100.000. Patients are initially treated medically, and colitis refractory to medical management is treated surgically, mostly by means of an (emergency) colectomy or a procto-colectomy with ileal J-pouch anastomosis. Over the past 10 years evidence has been accumulating indicating that the appendix has an immunomodulatory role in patients with UC reducing the need for medication and perhaps even colectomy. Objective: The objective of this prospective observational cohort study is to evaluate the effect of appendectomy on the disease course of patients with active ulcerative colitis despite standard step-up treatment including biologicals compared to usual care. The second objective is to evaluate if it is possible to predict response to appendectomy based on preoperative radiological or endoscopic findings by comparing results to histological characteristics in the resection specimen. Study design: The design of the study is a multicentre prospective cohort study including patients with active UC despite standard step-up treatment including optimized biological treatment. Patients failing standard step-up medical treatment (including biologicals), that are discussed in the multidisciplinary meeting to be counselled for a JAK-inhibitor (e.g. tofacitinib, filgotinib) or restorative proctcolectomy with ileal-j pouch anastomosis, will be counselled for appendectomy as an alternative treatment option. All patients will undergo colonoscopy before the start of a new treatment according to current guidelines. Biopsies will be taken to histologically confirm ongoing inflammation. Cecal biopsies will be used to correlate histological findings to response to appendectomy. Patients will undergo assessment of the appendix by ultrasound before surgery. All patients will be followed according to study protocol. Study population: All patients of 16 years and older, with established diagnosis of UC and ongoing disease activity despite standard step-up treatment including optimized biological treatment that are counselled for medication switch to a small molecule JAK-inhibitor or colectomy, will also be counselled for experimental appendectomy. Patients not interested in appendectomy will be asked for consent to collect data according to study protocol and represent the control group. Group size calculations are based on an improvement in remission rates from 17% in the second line medical group to 40% in the appendectomy group. With a power of 80%, a 2-sided alpha of 0.05, and accounting for 10% loss to follow-up, a total of 67 patients are required in each group. Intervention: A laparoscopic appendectomy will be performed in day care setting using a laparoscopic endostapler including the cecal base. Comparison: Usual care consists of small molecule JAK-inhibitor (e.g. tofacitinib, filgotinib) or surgical treatment by restorative proctocolectomy with ileal J-pouch anastomosis. Main study parameters/objectives: The primary outcome parameter is the number of patients achieving remission (Total Mayo score ≤2) 12 months after appendectomy. Secondary endpoints are reduction of medical therapy, the disease activity as measured with the Mayo score, colectomy rate, the health related quality of life and costs (EQ-5D, EORTC-QLQ-C30-QL and IBDQ), and histological appendix characteristics predictive of response.

Conditions

Colitis, Ulcerative

Keywords

Appendectomy, Ulcerative Colitis

Outcome Measures

Primary Outcomes (1)

• Remission rate

  Steroid-free remission rate (Total Mayo Score ≤2, with no individual sub-score exceeding 1 point) 12 months after appendectomy without switch of therapy.

  12 months

Secondary Outcomes (8)

• Reduction of medical therapy including corticosteroids

  Every 3 months, up to 12 months

• Disease activity, as measured with the full Mayo score

  6 and 12 months

• Failure

  Every 3 months, up to 12 months

• Health related quality of life (EQ-5D)

  3, 6 and 12 months

• Disease specific quality of life (IBDQ)

  3, 6 and 12 months

Study Arms (4)

Laparoscopic appendectomy

EXPERIMENTAL

Laparoscopic appendectomy in therapy refractory ulcerative colitis patients after pre-operative endoscopic biopsies of the appendix

Procedure: Laparoscopic appendectomy; Procedure: Endoscopic appendix biopsies

Non-active UC

ACTIVE COMPARATOR

Patients with non-active ulcerative colitis planned for surveillance colonoscopy will have additional endoscopic appendix biopsies to evaluate the histological characteristics of the appendix.

Procedure: Endoscopic appendix biopsies

Healthy control

ACTIVE COMPARATOR

'Healthy control' patients (i.e. patients planned for colonoscopy for polyps) will have additional endoscopic appendix biopsies to evaluate the histological characteristics of the appendix.

Procedure: Endoscopic appendix biopsies

JAK-inhibitor

ACTIVE COMPARATOR

JAK-inhibitor in therapy-refractory ulcerative colitis patients

Procedure: Endoscopic appendix biopsies

Interventions

Laparoscopic appendectomy PROCEDURE

Surgery will be performed under general anaesthesia. The laparoscopic appendectomy can be performed with the use of 3 trocars; one subumbilical, one suprapubic and one in the lower right quadrant of the abdomen. The appendix is removed using a laparoscopic endostapler enabling a safe and complete appendectomy with the cross stapling line at coecal base. Laparoscopic appendectomy will be performed by a gastrointestinal surgeon with sufficient experience in laparoscopic appendectomies (\>20).

Laparoscopic appendectomy

Endoscopic appendix biopsies PROCEDURE

Appendix biopsies will only be taken when the scope easily slides into the lumen of the appendix (the scope will not be pushed into the appendix lumen)

Healthy control; JAK-inhibitor; Laparoscopic appendectomy; Non-active UC

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 16 years and older
• Established diagnosis of UC
• Active disease (defined both clinically and endoscopically as Mayo-score ≥5 with endoscopy score of 2 or 3) despite standard step-up treatment including biological treatment
• Obtained written informed consent
• Age 16 years and older
• UC patients with non-active disease (defined both clinically and endoscopically as Mayo-score ≤5 with endoscopy score of 0 or 1) or non-UC patients with polyps
• Planned colonoscopy
• Obtained written informed consent

You may not qualify if:

• Prior appendectomy or other abdominal surgery by laparotomy precluding safe appendectomy
• Suspicion of Crohn's disease.
• Toxic megacolon or severe acute colitis necessitating clinical admission.
• History or suspicion of colonic dysplasia or malignancy.
• Required daily oral prednisone dose exceeding 20 milligrams.
• Patients with active extra-intestinal infections, liver or kidney failure, mayor lung and heart co-morbidity.
• Insufficient command of Dutch or cognitively unable to complete Dutch questionnaires.
• Prior appendectomy.
• Suspicion of Crohn's disease.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• University Hospital Birmingham: collaborator

Study Sites (1)

Amsterdam UMC

Amsterdam, 1105AZ, Netherlands

Location

Related Publications (1)

• Visser E, Reijntjes MA, Heuthorst L, Stellingwerf ME, West R, van Dongen K, Crolla RMPH, van Dieren S, van der Bilt JDW, Bemelman WA, D'Haens GR, Buskens CJ; COSTA Study Group. Appendicectomy versus switching to a JAK inhibitor in inducing remission in patients with active ulcerative colitis after biologic therapy failure (COSTA): 1-year results of a multicentre, prospective, cohort study. Lancet Gastroenterol Hepatol. 2026 Jan 6:S2468-1253(25)00291-2. doi: 10.1016/S2468-1253(25)00291-2. Online ahead of print.

  PMID: 41512889 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Christianne Buskens, MD, PhD

  Amsterdam Medical Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Study Record Dates

• First Submitted: August 27, 2018
• First Posted: April 11, 2019
• Study Start: August 24, 2018
• Primary Completion: September 20, 2024
• Study Completion: September 20, 2024
• Last Updated: October 2, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)