Serial Endoscopic Surveillance & Direct Topical Antibiotics to Define the Role of Microbes in Anastomotic Healing (SES-DTA)

April 24, 2023 updated by: University of Chicago

A Multicenter, Phase II, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial of Serial Endoscopic Surveillance (SES) and Direct Topical Antibiotics (DTA) to Define the Role of Microbes in Anastomotic Healing

Rationale: The surgical complication of intestinal anastomotic leak remains a clear and present danger to patients despite advances in surgical technique and ever more powerful antibiotics. No surgeon is immune from this complication and leak rates have not changed in decades. The consequences of a leak (peritonitis, sepsis, death) can be so severe that in the case of rectal cancer, diverting ileostomies are routinely performed to divert the fecal stream away from the healing anastomosis. We have recently discovered that certain intestinal bacteria, with the capacity to express collagenase and cleave MMP9 (Matrix metallopeptidase 9) to its active collagen degrading form, play a key and causative role in anastomotic leak. These bacteria often escape elimination due to the failure of current antibiotic regimens and their delivery methods to remain functionally durable at anastomotic tissue sites.

Purpose: This phase II clinical trial will track, in real time, the process of anastomotic healing and its associated microbiome by performing serial endoscopic surveillance (SES) following rectal cancer resection. By capturing anastomotic images and the associated microbial and inflammatory mediators from anastomotic fluids via SES performed at three time points following rectal cancer resection, we will correlate healing to microbial composition and inflammatory mediator status. Patients will be randomized and, at each time point, will receive lavage of their anastomosis with either saline or a triple antibiotic solution (ciprofloxacin, metronidazole, neomycin). An anastomotic healing score captured during SES will be compared between the two treatment arms and correlated to microbial and inflammatory mediator analyses of fluid samples to determine how intestinal microbes influence the process of anastomotic healing.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES

  • Perform repeated postoperative endoscopy of anastomotic tissue sites in patients undergoing low anterior resection for rectal cancer with diverting ileostomy.
  • Demonstrate that SES can reliably discriminate those anastomoses that progress along a continuum toward normal healing versus those that heal pathologically when images are evaluated by a jury blinded to treatment.
  • Demonstrate that those anastomoses that are judged to progress pathologically harbor distinct microbial species and predictive inflammatory mediators.
  • Demonstrate that when anastomotic tissues are lavaged with antibiotics directly via endoscopy (ciprofloxacin, metronidazole, neomycin), microbial pathogens that escape conventional antibiotics are eliminated and anastomotic healing progresses normally.
  • Determine if the anastomotic healing score, microbial analyses, and/or inflammatory mediator analyses identify or predict symptomatic and clinically relevant anastomotic complications.

STUDY This is a randomized, multicenter study. All patients undergo resection of rectal cancer with a low anterior resection with anastomoses within 10cm of the anal verge and diverting ileostomy. Patients will undergo three endoscopies: one intra-operative endoscopy (POD0) and two post-operative endoscopies (POD3-7, POD12-28) (POD = post-operative day). During the SES procedure, the anastomosis will be lavaged with saline, the fluid will be collected by suction, images will be taken and then the anastomosis will be lavaged with either saline or an antibiotic solution composed of metronidazole, ciprofloxacin and neomycin. Patients' clinical courses will be followed through chart review for 6 to 7 months following surgery.

PROJECTED ACCRUAL A total of 200 patients (approximately 100 per treatment arm) will be accrued for this study within 4 years.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  • Diagnosis of rectal cancer
  • Scheduled to undergo a low anterior resection (with the planned anastomosis within 10cm of the anal verge) and a diverting ileostomy
  • 18 years of age or older
  • Able to provide informed consent

Exclusion Criteria

  • Prior medical history of or suspected diagnosis of inflammatory bowel disease or irritable bowel syndrome
  • Pregnant or breastfeeding
  • Allergy to lidocaine, ciprofloxacin, metronidazole or neomycin

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cipro, metronidazole, neomycin combo
As part of each serial endoscopic surveillance, a second lavage of the anastomosis will be performed prior to removing the endoscope. In this arm, the lavage will be with a direct topical antibiotics solution composed of metronidazole, ciprofloxacin and neomycin.
Drug: Cipro, metronidazole, neomycin combo
During endoscopies after imaging, the anastomosis will be lavaged with an antibiotic solution composed of metronidazole, ciprofloxacin and neomycin
Other Names:
  • Cipro/CiproXR/CiproIV; Flagyl/FlagylER/Metro; Neomycin
Procedure: Serial Endoscopic Surveillance
Patients will undergo serial endoscopic surveillance consisting of three endoscopies: one intra-operative endoscopy (POD0) and two post-operative endoscopies (POD3-7, POD12-28). During endoscopies, the anastomosis will be lavaged with saline, the fluid will be collected by suction and images will be taken.
Other Names:
  • SES
Placebo Comparator: Saline
As part of each serial endoscopic surveillance, a second lavage of the anastomosis will be performed prior to removing the endoscope. In this arm, the lavage will be with direct topical saline.
Procedure: Serial Endoscopic Surveillance
Patients will undergo serial endoscopic surveillance consisting of three endoscopies: one intra-operative endoscopy (POD0) and two post-operative endoscopies (POD3-7, POD12-28). During endoscopies, the anastomosis will be lavaged with saline, the fluid will be collected by suction and images will be taken.
Other Names:
  • SES
Drug: Saline
During endoscopies after imaging, the anastomosis will be lavaged with a placebo direct topical saline solution
Other Names:
  • 0.9% saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Anastomotic Healing Score (ordinal scale ranging from 0 to a maximum of 18)
Time Frame: Post-operative day 12-28
Post-operative day 12-28

Secondary Outcome Measures

Outcome Measure
Time Frame
Anastomotic Healing Score (ordinal scale ranging from 0 to a maximum of 18)
Time Frame: Post-operative day 0
Post-operative day 0
Anastomotic Healing Score (ordinal scale ranging from 0 to a maximum of 18)
Time Frame: Post-operative day 3-7
Post-operative day 3-7

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Chicago

Investigators

  • Principal Investigator: John C Alverdy, MD, University of Chicago

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 3, 2017

Primary Completion (Actual)

March 3, 2017

Study Completion (Actual)

March 3, 2017

Study Registration Dates

First Submitted

February 8, 2016

First Submitted That Met QC Criteria

February 10, 2016

First Posted (Estimate)

February 15, 2016

Study Record Updates

Last Update Posted (Actual)

April 26, 2023

Last Update Submitted That Met QC Criteria

April 24, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB15-0971

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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