COlonic Salvage by Therapeutic Appendectomy.

Colitis, Ulcerative Clinical Trial

— COSTA  

Official title:

The Effect of Appendectomy in Ulcerative Colitis Patients With Active Disease: COlonic Salvage by Therapeutic Appendectomy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03912714
• Other study ID #: 2018_058
• Status: Recruiting
• Phase: N/A
• Start date: August 24, 2018
• Est. completion date: September 2020

Study information

• Verified date: April 2019
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: Willem Bemelman, MD, PhD
• Phone: 0031207326818
• Email: w.a.bemelman[@]amc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 proctocolectomy 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. The second objective is to determine if histological inflammation in the appendix resection specimens can be reliably predicted by pre-operative endoscopic biopsies of the appendix and correlated to clinical and pathological response after appendectomy.

Study design: The design of the study is a prospective observational cohort study of 80 consecutive patients.

Study population: Sixty patients of 18 years and older, with established diagnosis of UC and ongoing disease activity despite standard step-up treatment including biologicals. Furthermore, histological characteristics in appendix biopsies of 10 patients with non-active UC and 10 'healthy control' patients (e.g. patients undergoing endoscopy for polyps) will be evaluated and used as a reference control group.

Intervention: Patients will undergo laparoscopic appendectomy in clinical or day care setting.

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.

Description:

The study is designed as a prospective observational series including patients with active ulcerative colitis despite standard step-up treatment including biologicals. Sixty consecutive patients who are refractory to medical treatment will be recruited to evaluate the effect of the appendectomy on the disease course.

Eligible patients will be counselled at the outpatient clinics. Patients with presumed therapy-refractory inflammation will undergo ileocolonoscopy, which is part of standard daily practice. When informed consent is given, the presence of a PARP will be documented, and additional biopsies of the appendix and coecal base will be taken, to determine histological inflammation grade. Active disease is required for inclusion, and is defined as a combined clinical and endoscopic Mayo-score of ≥5 with an endoscopic subscore of 2 or 3. After inclusion, a laparoscopic appendectomy will be performed within 9 weeks. Patients will be followed every 3 months after laparoscopic appendectomy to assess the patients' clinical condition and the non-invasive Mayo score. According to standard practice evaluating therapy change, a sigmoidoscopy will be performed within 6 months and a full ileocolonoscopy at 12 months, including biopsies of the colon and coecal base, to assess mucosal appearance and complete the Mayo score.

Postoperatively, patients will receive the similar medical treatment as given pre-appendectomy. If medication can be tapered post-appendectomy, this will be done according to the experience of the treating physician and current guidelines. Patients will complete health related quality of life questionnaires (EQ-5D, EORTC-QLQ-C30-QL and IBDQ) via email or a telemedicine application (MyIBDcoach) at inclusion and at 3, 6 and 12 months follow-up.

The pre-operative endoscopic biopsies of the appendix will be used to determine if histological inflammation in the appendix resection specimens can be reliably predicted. Histological findings in the resection specimens will be correlated to clinical and pathological response after appendectomy. Furthermore, in 20 patients who are planned for colonoscopy (10 patients with non-active UC and 10 non-UC patients with polyps) additional appendix biopsies will be taken to use as a reference control group. Therefore, a total of 80 patients will be recruited for this study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: September 2020
• Est. primary completion date: September 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria (study group)

• Age 18 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 biologicals

• Obtained written informed consent

Inclusion criteria (control group)

• Age 18 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

• Open appendix lumen with diameter large enough to slide scope in

• Obtained written informed consent

Exclusion criteria (study group)

• Prior appendectomy or other abdominal surgery by laparotomy.

• Suspicion of Crohn's disease.

• Toxic megacolon or severe acute colitis necessitating clinical admission

• 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

Exclusion criteria (control group)

• Prior appendectomy.

• Suspicion of Crohn's disease.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer

Intervention

Procedure:
• Laparoscopic appendectomy
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).
• Endoscopic appendix biopsies
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)

Locations

Country	Name	City	State
Netherlands	Amsterdam UMC	Amsterdam

Sponsors (2)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	University Hospital Birmingham

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endoscopic remission rate	Remission rate after appendectomy according to the MAYO score defined as 0-1 (including endoscopic remission)	12 months
Secondary	Stoppage of medical therapy.	Downscaling of medical therapy including corticosteroids (number of patients that stop medication).	Every 3 months, up to 12 months
Secondary	Disease activity, as measured with the full Mayo score	Using this 12-point scoring system, disease activity is evaluated based on stool frequency, rectal bleeding, the physician's global assessment, and endoscopic appearance. Each subscale is ranging from 0-3 and higher values represent worse outcomes. The full Mayo score is computed by the sum of the four subscores.	6 and 12 months
Secondary	Failure	Defined as colectomy or start of trial medication.	Every 3 months, up to 12 months
Secondary	Health related quality of life (EQ-5D)	This questionnaire is a simple, generic instrument for describing and valuing health related quality of life. It includes 5 items (mobility, personal care, daily activities, pain, and anxiety/ depression) that are answered on a 3-point scale ranging from no problems (level 1) to extreme problems (level 3).	3, 6 and 12 months
Secondary	Disease specific quality of life (IBDQ)	A disease-specific questionnaire that measures quality of life in 4 domains (bowel symptoms, systemic symptoms, social function, and emotional function). The IBDQ consists of 32 questions which are rated on a scale from 1 to 7, resulting in a total score ranging from 32 to 224 and a higher score represents a better quality of life.	3, 6 and 12 months
Secondary	Global quality of life (ORTC-QLQ-C30-QL)	This sub questionnaire contains the 2 items of the global quality of life dimension of the EORTC-QLQ-C30 questionnaire. It includes 30 questions, and answers are ranging from no problems (1 point) to extreme problems (4 points).	3, 6 and 12 months
Secondary	Time to remission	Time between inclusion and remission	Every 3 months, up to 12 months
Secondary	Pathological analysis of resection specimen to determine histological characteristics according to the Geboes score, predictive of response .	Geboes score less than 3: (grade 0-5: architectural changes, increase of chronic inflammatory infiltrate, increase of eosinophils in the lamina propria, increase of neutrophils in the lamina propria, involvement of neutrophils in the epithelium (cryptitis), crypt destruction, and erosion or ulcerations)	Baseline