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COlonic Salvage by Therapeutic Appendectomy. (COSTA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03912714
Recruitment Status : Recruiting
First Posted : April 11, 2019
Last Update Posted : April 11, 2019
Sponsor:
Collaborator:
University Hospital Birmingham
Information provided by (Responsible Party):
Prof. dr. W.A. Bemelman, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

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 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.


Condition or disease Intervention/treatment Phase
Colitis, Ulcerative Procedure: Laparoscopic appendectomy Procedure: Endoscopic appendix biopsies Not Applicable

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effect of Appendectomy in Ulcerative Colitis Patients With Active Disease: COlonic Salvage by Therapeutic Appendectomy
Actual Study Start Date : August 24, 2018
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Laparoscopic appendectomy
Laparoscopic appendectomy in therapy refractory ulcerative colitis patients after pre-operative endoscopic biopsies of the appendix
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).

Procedure: 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)

Active Comparator: Non-active UC
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
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)

Active Comparator: Healthy control
'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
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)




Primary Outcome Measures :
  1. Endoscopic remission rate [ Time Frame: 12 months ]
    Remission rate after appendectomy according to the MAYO score defined as 0-1 (including endoscopic remission)


Secondary Outcome Measures :
  1. Stoppage of medical therapy. [ Time Frame: Every 3 months, up to 12 months ]
    Downscaling of medical therapy including corticosteroids (number of patients that stop medication).

  2. Disease activity, as measured with the full Mayo score [ Time Frame: 6 and 12 months ]
    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.

  3. Failure [ Time Frame: Every 3 months, up to 12 months ]
    Defined as colectomy or start of trial medication.

  4. Health related quality of life (EQ-5D) [ Time Frame: 3, 6 and 12 months ]
    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).

  5. Disease specific quality of life (IBDQ) [ Time Frame: 3, 6 and 12 months ]
    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.

  6. Global quality of life (ORTC-QLQ-C30-QL) [ Time Frame: 3, 6 and 12 months ]
    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).

  7. Time to remission [ Time Frame: Every 3 months, up to 12 months ]
    Time between inclusion and remission

  8. Pathological analysis of resection specimen to determine histological characteristics according to the Geboes score, predictive of response . [ Time Frame: Baseline ]
    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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03912714


Contacts
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Contact: Willem Bemelman, MD, PhD 0031207326818 w.a.bemelman@amc.nl
Contact: Lianne Heuthorst, MD 0031205662860 l.heuthorst@amc.uva.nl

Locations
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Netherlands
Amsterdam UMC Recruiting
Amsterdam, Netherlands, 1105AZ
Contact: Lianne Heuthorst, MD       l.heuthorst@amc.uva.nl   
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
University Hospital Birmingham
Investigators
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Principal Investigator: Christianne Buskens, MD, PhD Amsterdam Medical Centre

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Responsible Party: Prof. dr. W.A. Bemelman, Prof. dr., Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT03912714    
Other Study ID Numbers: 2018_058
First Posted: April 11, 2019    Key Record Dates
Last Update Posted: April 11, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Prof. dr. W.A. Bemelman, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Appendectomy, Ulcerative Colitis
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases