AppenDectomy Vs ANti TNF-a in Inducing Clinical and EnDoscopic Remission in Left-sided Ulcerative Colitis

Ulcerative Colitis Clinical Trial

— ADVANCED-UC  

Official title:

ADVANCED-UC TRIAL: AppenDectomy Vs ANti TNF-a in Inducing Clinical and EnDoscopic Remission in Left-sided Ulcerative Colitis - A Randomized Clinical Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05931458
• Other study ID #: 340/21
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 1, 2023
• Est. completion date: July 1, 2028

Study information

• Verified date: June 2023
• Source: Federico II University
• Contact: Gaetano Luglio, Prof
• Phone: 00390817462775
• Email: gaetano.luglio[@]unina.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Ulcerative Colitis (UC) is a chronic Inflammatory Bowel Disease (IBD) characterized by a multifactorial etiology, a variable involvement of large bowel, and a relapsing-remitting course.

In order to keep the disease in a "quiescent" status and to prevent relapses, a significative percentage of UC patients will remain on long-term drug therapy. However, long-term immunosuppressant therapy is not free of risks and complications: in fact, these therapies have an impact on both healthcare system resources and patients' quality of life; more, there are even concerns regarding the side effects of long-term immunosuppressant therapy.

Over the past 20 years, a considerable amount of evidence was produced to support the immunomodulatory role of the appendix in the development and course of UC: there is a strong inverse relationship between previous appendectomy and development of the UC. One of the proposed theories to justify this link is that the appendix could act as a reservoir for commensal bacteria that can be secreted into the colon, affecting its microbiome and immunological response; another theory describes the appendix as the "priming site" for the cytokine production and the immunological cascade that may trigger inflammation in colon and rectum.

The idea of this study moves from these assumptions: the investigators aim to evaluate the impact of appendectomy in patients with UC who are candidates to the treatment with biologics (Anti TNF-a), because of conventional therapies failure. To further reduce any ethical problems and significantly lower any surgical morbidity, investigators will restrict the study population to only patients with active left-sided colitis, so that the surgery for appendectomy will take place on a non-inflamed cecum.

By undertaking this study, the investigators hope to a) learn more about the role of appendix and the impact of appendectomy in the clinical history of Ulcerative Colitis; b) demonstrate that laparoscopic appendectomy, a relatively simple surgical procedure that can also be performed in day-surgery with a very low expected complication rate, is a treatment that is superior to biological therapy, avoiding patients starting a chronic, long-lasting therapy, with the consequent risk of immunosuppression, and with possible higher costs for the health system in the long term.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 94
• Est. completion date: July 1, 2028
• Est. primary completion date: July 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients aged 18 or above

• Patients with a confirmed diagnosis of left-sided UC (extended up to the mid transverse colon)

• Patients with active disease refractory to conventional treatment and candidates for anti- TNF-a treatment

• Patients who have given consent to the surgical procedure

Exclusion Criteria:

• Patients under the age of 18

• Lack of diagnostic certainty of Ulcerative Colitis / Crohn's disease diagnostic doubt

• Patients who previously received appendectomy

• Patients who have had previous laparotomic abdominal surgery, which could make the appendectomy more complex

• Patients with Severe Acute Colitis/Toxic Megacolon

• Patients who have not given their consent to the intervention

• Patients who receive a different surgical procedure from appendectomy because of intraoperative complications

• Pregnant patients

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Procedure:
• Appendectomy
Laparoscopic appendectomy is a relatively simple surgical procedure that can be performedby most surgeons, either on an outpatient basis or with a single-night hospital stay. The laparoscopic approach is now the recommended option due to faster recovery times and fewer wound complications.

Drug:
• Infliximab
Administration of Infliximab (Anti-TNF-a biologic drug)

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Federico II University	Crohn's and Colitis Foundation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Steroid Free Clinical Remission	Steroid Free Clinical Remission at 3 and 12 months (defined as Partial Mayo score	3 months
Primary	Steroid Free Clinical Remission	Steroid Free Clinical Remission at 3 and 12 months (defined as Partial Mayo score	12 months
Primary	Endoscopic remission	Endoscopic remission at 3 and 12 months (defined as MAYO CU score	3 months
Primary	Endoscopic remission	Endoscopic remission at 3 and 12 months (defined as MAYO CU score	12 months
Primary	Assessment of Quality of Life	Assessment of Quality of Life at 3 and 12 months, through the SIBDQ (Short Inflammatory Bowel Disease Questionnaire, ranging from 10, meaning poor quality of life, to 70, meaning optimal quality of life)	3 months
Primary	Assessment of Quality of Life	Assessment of Quality of Life at 3 and 12 months, through the SIBDQ (Short Inflammatory Bowel Disease Questionnaire, ranging from 10, meaning poor quality of life, to 70, meaning optimal quality of life)	12 months
Primary	Assessment of Quality of Life	Assessment of Quality of Life at 3 and 12 months, through the SF-36 questionnaire (Short-form 36)	3 months
Primary	Assessment of Quality of Life	Assessment of Quality of Life at 3 and 12 months, through the SF-36 questionnaire (Short-form 36)	12 months
Secondary	Clinical Response	Clinical Response at 3 and 12 months (defined as a reduction of the MAYO SCORE of at least 3points). MAYO SCORE ranges from 0 (inactive disease) to 3 (severe disease activity).	3 months
Secondary	Clinical Response	Clinical Response at 3 and 12 months (defined as a reduction of the MAYO SCORE of at least 3points). MAYO SCORE ranges from 0 (inactive disease) to 3 (severe disease activity).	12 months
Secondary	Failure rate	Evaluation of the failure rate at 3, 12 and 24 months (evaluated as the rate of use of the biological or colectomy in the "treatment" group, as the rate of use of a second biological or colectomy in the "control" group)	3 months
Secondary	Failure rate	Evaluation of the failure rate at 3, 12 and 24 months (evaluated as the rate of use of the biological or colectomy in the "treatment" group, as the rate of use of a second biological or colectomy in the "control" group)	12 months
Secondary	Failure rate	Evaluation of the failure rate at 3, 12 and 24 months (evaluated as the rate of use of the biological or colectomy in the "treatment" group, as the rate of use of a second biological or colectomy in the "control" group)	24 months
Secondary	Complication assessment	Complication assessment: Treatment-related serious adverse events will be compared between the two groups. The Dindo-Clavien Classification will be used within 30 days of the procedure in patientsundergoing appendectomy. For patients undergoing biologics, the cumulative rate of treatment- related serious adverse events up to 12 months will be considered. Hospitalization rates will also be assessed as a consequence of adverse events to treatment.	30 days
Secondary	Complication assessment	Complication assessment: Treatment-related serious adverse events will be compared between the two groups. The Dindo-Clavien Classification will be used within 30 days of the procedure in patientsundergoing appendectomy. For patients undergoing biologics, the cumulative rate of treatment- related serious adverse events up to 12 months will be considered. Hospitalization rates will also be assessed as a consequence of adverse events to treatment.	12 months
Secondary	Histological remission	Evaluation of histological remission at 3 and 12 months with the Geboes score (ranging from 0, histological remission, to 22, severe inflammatory injury).; In patients undergoing appendectomy, the appendix will also be histologically evaluated with the same Geboes score in addition to the presence of PARP (peri-appendicular patches).	3 months
Secondary	Histological remission	Evaluation of histological remission at 3 and 12 months with the Geboes score (ranging from 0, histological remission, to 22, severe inflammatory injury).; In patients undergoing appendectomy, the appendix will also be histologically evaluated with the same Geboes score in addition to the presence of PARP (peri-appendicular patches).	12 months
Secondary	Immunohistochemical evaluation	Immunohistochemical evaluation of the IgA / IgG ratio and correlation between the findings onthe appendix and the findings on colonic biopsy at 3 and 12 months.	3 months
Secondary	Immunohistochemical evaluation	Immunohistochemical evaluation of the IgA / IgG ratio and correlation between the findings onthe appendix and the findings on colonic biopsy at 3 and 12 months.	12 months
Secondary	Colectomy rate	Evaluation of "Colectomy rate" at 12, 24 and 60 months	12 months
Secondary	Colectomy rate	Evaluation of "Colectomy rate" at 12, 24 and 60 months	24 months
Secondary	Colectomy rate	Evaluation of "Colectomy rate" at 12, 24 and 60 months	60 months