Minimally Invasive vs Open Surgery for Ulcerative Colitis

(FUNCTIon Trial)

Recruiting in Palo Alto (17 mi)

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Mount Sinai Hospital, Canada

Must not be taking: Steroids

Disqualifiers: Colorectal cancer, PSC, FAP, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

Background: Ulcerative colitis (UC) and inflammatory bowel unclassified (IBDu) are inflammatory bowel diseases (IBD) involving the colon and rectum. It is a chronic disease occurring in young people with a high burden on social and professional life. Although treated medically by immunomodulatory drugs, about 15 - 20% of UC patients will need an ileal pouch-anal anastomosis (IPAA). In primary cases, this procedure is usually performed laparoscopically (further called transabdominal IPAA or tabd-IPAA). More recently even less invasive surgical techniques have emerged, using a trans-anal access, facilitating dissection of the distal rectum. Although transanal access is associated with a good postoperative outcome profile, there is very limited data on functional outcome in patients with a trans-anal ileal pouch-anal anastomosis surgery (ta-IPAA). Objective: The objective of this study is to determine if functional outcome following ta-IPAA is the same as or better than postoperative function after tabd-IPAA with UC and IBDu. Study design: The FUNCTIon trial is a non-inferiority randomized, controlled trial that will involve 3 hospitals across North-America and Europe. Patient population: All patients with UC and IBDu eligible for pelvic pouch procedure will be randomized to either ta-IPAA or tabd-IPAA. Prior to the start of the study REB will be obtained at all centres and informed consent will be obtained from all patients. The inclusion criteria for the study are: patients between 18 and 60 years old with UC or IBD unclassified (IBDu) eligible for surgery. They will need to speak either English or the primary language of the center they are treated at. The exclusion criteria for the study are: contraindication for laparoscopy, familial adenomatous polyposis (FAP), colorectal cancer, presence of primary sclerosing cholangitis (PSC), a hand-sewn ileo-anal anastomosis, immunomodulating therapy including steroids, pregnancy and lactating, urgent indication. Intervention: ta-IPAA or tabd-IPAA. Outcomes: Primary outcome is the functional outcome at one year after pelvic pouch surgery. This will be measured using the validated Colorectal Functional Outcome (COREFO) questionnaire. Secondary outcomes are functional outcome at 3 and 6 months, male and female sexual function, perioperative measures and clinical measures. Sample Size: A sample of 48 (24 per group) is required to detect a between-group non-inferiority margin of 7.05 in COREFO score with a 1-sided α of 0.05 and a power of 80%, allowing for 20% attrition. A participation rate of 50% is anticipated. Analysis: All continuous variable outcomes will be compared using analysis of covariance. Categorical variable outcomes will be analyzed using repeated measures logistic regression. Proportional outcomes will be analyzed with the chi-square or Fisher's exact test and continuous variables will be analyzed with student's t-test. Follow-up: Each participant will be followed up at 6 weeks, 3 months, 6 months and 12 months after the intervention to assess functional scores and clinical events. Perioperative events (including postoperative complications) will be assessed during the intervention hospitalization period.

Will I have to stop taking my current medications?

The trial requires that patients stop taking immunomodulating therapy, including steroids, before surgery. There is an 8-week washout period (time without taking certain medications) for all treatments before the pouch construction.

What data supports the effectiveness of the treatment for ulcerative colitis?

Research shows that ileal pouch-anal anastomosis (IPAA) is effective for treating chronic ulcerative colitis, with studies indicating good long-term outcomes and quality of life for patients. Comparisons between laparoscopic and open surgery approaches suggest similar effectiveness, with differences mainly in recovery and postoperative responses. ^{1 2 3 4 5}

Is ileal pouch-anal anastomosis (IPAA) surgery safe for ulcerative colitis?

Research shows that both minimally invasive (laparoscopic) and open IPAA surgeries are generally safe for treating ulcerative colitis, with studies comparing their safety and short-term outcomes. However, there is a risk of complications like pouch-related cancers, which have been documented since 1990. ^{1 2 3 6 7}

How is the ileal pouch-anal anastomosis (IPAA) treatment for ulcerative colitis different from other treatments?

The ileal pouch-anal anastomosis (IPAA) is a unique surgical treatment for ulcerative colitis that involves creating a pouch from the small intestine to restore bowel function after removing the colon and rectum. Unlike other treatments, it is a surgical option that can significantly improve quality of life by allowing patients to avoid a permanent ileostomy (an opening in the belly for waste to exit the body). ^{1 4 8 9 10}

Research Team

Eligibility Criteria

This trial is for adults aged 18-60 with Ulcerative Colitis or IBD unclassified, who need surgery and haven't responded to medical therapy. They must speak English or the center's primary language and give informed consent. Excluded are those with certain genetic conditions, cancer, severe lung disease, pregnancy, lactation, steroid use without an 8-week washout period before surgery.

Inclusion Criteria

Provide informed consent

My treatment plan involves 1 to 3 stages.

Speak English and/or primary language of recruiting center

Exclusion Criteria

Pregnancy and lactation (tested by a urinary pregnancy test)

I need surgery that involves hand-stitching parts of my intestines together.

I am scheduled for or have had redo-pouch surgery.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intervention

Participants undergo either transanal or transabdominal ileal pouch-anal anastomosis (IPAA) surgery

Hospitalization period

In-hospital stay for surgery and initial recovery

Postoperative Monitoring

Participants are monitored for perioperative events and complications

30 days

Regular in-person visits as per hospital protocol

Follow-up

Participants are monitored for functional outcomes and clinical events

12 months

Follow-up visits at 6 weeks, 3 months, 6 months, and 12 months

Treatment Details

Interventions

• Transanal and Laparoscopic or Open Ileal Pouch-Anal Anastomosis (Surgery)

Trial Overview The FUNCTIon trial compares two surgical techniques for creating a pelvic pouch in patients: transanal (ta-IPAA) versus laparoscopic (tabd-IPAA). It aims to see if ta-IPAA has equal or better functional outcomes after one year using the COREFO questionnaire. The study will randomly assign participants to either group across three hospitals.

Participant Groups

Group I: transanal IPAA Experimental Treatment 1 Intervention

In the experimental arm, patients will undergo transanal dissection of the distal part of the rectum. After proctectomy, an ileal pouch-anal anastomosis (IPAA) will be created. A Gelpoint Path will be used to create access through the anus. Postoperative care will occur following the hospital specific protocols.

Group II: transabdominal IPAA Active Control 1 Intervention

In the control group, proctectomy will occur through abdominal dissection (laparoscopy, single port laparoscopy, robotic or open). Postoperative care will occur following the hospital specific protocols.

Transanal and Laparoscopic or Open Ileal Pouch-Anal Anastomosis is already approved in Canada for the following indications:

Approved in Canada as Ileal Pouch-Anal Anastomosis for:

• Ulcerative Colitis
• Familial Adenomatous Polyposis
• Inflammatory Bowel Disease Unclassified

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Mount Sinai Hospital Toronto, Canada

Who Is Running the Clinical Trial?

Mount Sinai Hospital, Canada

Lead Sponsor

Trials

210

Patients Recruited

70,700+

Universitaire Ziekenhuizen KU Leuven

Collaborator

Trials

1048

Patients Recruited

1,658,000+

Janindra Warusavitarne

Collaborator

Trials

1

Patients Recruited

50+

Gabriele Bislenghi

Collaborator

Trials

1

Patients Recruited

50+

Andre D'Hoore

Collaborator

Trials

1

Patients Recruited

50+

Cedars-Sinai Medical Center

Collaborator

Trials

523

Patients Recruited

165,000+

St Mary's Hospital, London

Collaborator

Trials

10

Patients Recruited

8,800+

Mantaj S. Brar

Collaborator

Trials

1

Patients Recruited

50+

Philip Fleshner

Collaborator

Trials

1

Patients Recruited

50+

Karen Zaghiyan

Collaborator

Trials

1

Patients Recruited

50+

Findings from Research

In a study of 1310 patients who underwent hand-sewn ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, postoperative complications decreased significantly over time, with pelvic sepsis rates dropping from 7% to 3% between 1981-1985 and 1991-1994.

After an average follow-up of 6.5 years, the functional outcomes remained stable, with patients averaging 5 stools per day, but the cumulative probability of pouch failure increased to 9% by 10 years, indicating that while complications may decrease with experience, long-term pouch failure rates can rise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

J ileal pouch-anal anastomosis for chronic ulcerative colitis: complications and long-term outcome in 1310 patients. Meagher, AP., Farouk, R., Dozois, RR., et al.[2022]

Patients undergoing laparoscopic ileal pouch anal anastomosis (LAP-IPAA) experienced faster recovery times, including shorter times to first walking and food intake compared to those who had open IPAA, indicating a more efficient postoperative recovery process.

LAP-IPAA was associated with significantly lower levels of inflammatory markers (interleukin-6, interleukin-1ra, and C-reactive protein) shortly after surgery, suggesting that it results in a reduced systemic inflammatory response compared to open IPAA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Acute-phase Response in Laparoscopic and Open Ileal Pouch Anal Anastomosis in Patients With Ulcerative Colitis: A Case-matched Comparative Study. Okita, Y., Araki, T., Hiro, J., et al.[2015]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laparoscopic 3-step restorative proctocolectomy: comparative study with open approach in 45 patients. Ouaïssi, M., Lefevre, JH., Bretagnol, F., et al.[2008]

After 30 years, 93.3% of patients who underwent ileal pouch-anal anastomosis (IPAA) still had a functioning pouch, demonstrating the long-term durability of this surgical procedure for chronic ulcerative colitis.

Quality of life scores remained stable over the 30 years post-surgery, indicating that while stool frequency increased slightly, overall functional outcomes and patient satisfaction did not significantly decline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results at Up to 30 Years After Ileal Pouch-Anal Anastomosis for Chronic Ulcerative Colitis. Lightner, AL., Mathis, KL., Dozois, EJ., et al.[2018]

Ileal pouch anal anastomosis (IPAA) is a highly effective treatment for chronic ulcerative colitis and other related conditions, with 95% of patients reporting good or excellent functional outcomes and quality of life after surgery.

In a study of 3707 patients, early complications occurred in 33.5% of cases, but the mortality rate was very low at 0.1%, indicating that while there are risks, IPAA is generally safe and has a low pouch failure rate of 5.3%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ileal pouch anal anastomosis: analysis of outcome and quality of life in 3707 patients. Fazio, VW., Kiran, RP., Remzi, FH., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, feasibility, and short-term outcomes of laparoscopic ileal-pouch-anal anastomosis: a single institutional case-matched experience. Larson, DW., Cima, RR., Dozois, EJ., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of cuff and pouch cancer in patients with ileal pelvic pouch for ulcerative colitis. Selvaggi, F., Pellino, G., Canonico, S., et al.[2018]

A survey of 40 Canadian and 873 American colorectal surgeons revealed that Canadian surgeons are more likely to perform ileal pouch anal anastomosis (IPAA) alone (44%) compared to American surgeons (26%) when a tension-free IPAA is possible after prior colectomy.

In cases involving patients on high doses of prednisone, Canadian surgeons preferred subtotal colectomy with end ileostomy (45%) significantly more than American surgeons (14%), indicating notable differences in surgical approaches between the two countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical management of ulcerative colitis: a comparison of Canadian and American colorectal surgeons. Richardson, D., deMontbrun, S., Johnson, PM.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ileal pouch-anal anastomosis (IPAA): functional outcome after postoperative pelvic sepsis. A prospective study of 100 patients. Hallberg, H., Ståhlberg, D., Akerlund, JE.[2018]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ileal pouch-anal anastomosis in ulcerative colitis: outcomes, functional results, and quality of life in patients with more than 10-year follow-up. Carcamo, L., Miranda, P., Zúñiga, A., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

J ileal pouch-anal anastomosis for chronic ulcerative colitis: complications and long-term outcome in 1310 patients. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Systemic Acute-phase Response in Laparoscopic and Open Ileal Pouch Anal Anastomosis in Patients With Ulcerative Colitis: A Case-matched Comparative Study. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Laparoscopic 3-step restorative proctocolectomy: comparative study with open approach in 45 patients. [2008]

4. England pubmed.ncbi.nlm.nih.gov

Results at Up to 30 Years After Ileal Pouch-Anal Anastomosis for Chronic Ulcerative Colitis. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Ileal pouch anal anastomosis: analysis of outcome and quality of life in 3707 patients. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Safety, feasibility, and short-term outcomes of laparoscopic ileal-pouch-anal anastomosis: a single institutional case-matched experience. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Systematic review of cuff and pouch cancer in patients with ileal pelvic pouch for ulcerative colitis. [2018]

8. Canada pubmed.ncbi.nlm.nih.gov

Surgical management of ulcerative colitis: a comparison of Canadian and American colorectal surgeons. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Ileal pouch-anal anastomosis (IPAA): functional outcome after postoperative pelvic sepsis. A prospective study of 100 patients. [2018]

10. Germany pubmed.ncbi.nlm.nih.gov

Ileal pouch-anal anastomosis in ulcerative colitis: outcomes, functional results, and quality of life in patients with more than 10-year follow-up. [2021]