Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 11 of 61 for:    Neomycin sulfate

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

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: NCT02682485
Recruitment Status : Not yet recruiting
First Posted : February 15, 2016
Last Update Posted : March 15, 2018
Sponsor:
Information provided by (Responsible Party):
University of Chicago

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Anastomotic Leak Rectal Cancer Drug: Cipro, metronidazole, neomycin combo Procedure: Serial Endoscopic Surveillance Drug: Saline Phase 2

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: 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
Estimated Study Start Date : January 1, 2020
Estimated Primary Completion Date : December 1, 2022
Estimated Study Completion Date : July 1, 2023


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 Name: 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 Name: 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 Name: SES

Drug: Saline
During endoscopies after imaging, the anastomosis will be lavaged with a placebo direct topical saline solution
Other Name: 0.9% saline solution




Primary Outcome Measures :
  1. Anastomotic Healing Score (ordinal scale ranging from 0 to a maximum of 18) [ Time Frame: Post-operative day 12-28 ]

Secondary Outcome Measures :
  1. Anastomotic Healing Score (ordinal scale ranging from 0 to a maximum of 18) [ Time Frame: Post-operative day 0 ]
  2. Anastomotic Healing Score (ordinal scale ranging from 0 to a maximum of 18) [ Time Frame: Post-operative day 3-7 ]


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.


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

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

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): NCT02682485


Contacts
Layout table for location contacts
Contact: Anna Alecci 773.702.0316 aalecci@surgery.bsd.uchicago.edu
Contact: Kristina Guyton, MD kristina.guyton@uchospitals.edu

Sponsors and Collaborators
University of Chicago
Investigators
Layout table for investigator information
Principal Investigator: John C Alverdy, MD University of Chicago

Publications:
Layout table for additonal information
Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT02682485     History of Changes
Other Study ID Numbers: IRB15-0971
First Posted: February 15, 2016    Key Record Dates
Last Update Posted: March 15, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Chicago:
Rectal Cancer
low anterior resection
SES
SES-DTA
anastomotic leak
anastomotic healing
intestinal healing
anastomosis

Additional relevant MeSH terms:
Layout table for MeSH terms
Neomycin
Rectal Neoplasms
Anastomotic Leak
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Postoperative Complications
Pathologic Processes
Anti-Bacterial Agents
Metronidazole
Ciprofloxacin
Antibiotics, Antitubercular
Pharmaceutical Solutions
Anti-Infective Agents
Antitubercular Agents
Antiprotozoal Agents
Antiparasitic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors