Anastomotic LeakPhase 2SES-DTANCT02682485
Serial Endoscopic Surveillance & Direct Topical Antibiotics to Define the Role of Microbes in Anastomotic Healing
A Phase 2 study testing Cipro, metronidazole, neomycin combo, Serial Endoscopic Surveillance and Saline in people with Anastomotic Leak and Rectal Cancer, run by University of Chicago.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anastomotic Leak, Rectal Cancer
- What is being tested?
- Cipro, metronidazole, neomycin combo, Serial Endoscopic Surveillance and Saline
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 3 Mar 2017to 3 Mar 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
About this study
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
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.
Read the 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.
- Conditions
- Anastomotic Leak, Rectal Cancer
- Being tested
- Cipro, metronidazole, neomycin combo, Serial Endoscopic Surveillance, Saline
- Keywords
- Rectal Cancer, low anterior resection, SES, SES-DTA, anastomotic leak, anastomotic healing, intestinal healing, anastomosis
- Medical subject headings
- Anastomotic Leak, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cipro, metronidazole, neomycin comboDrug
Also called Cipro/CiproXR/CiproIV; Flagyl/FlagylER/Metro; Neomycin
During endoscopies after imaging, the anastomosis will be lavaged with an antibiotic solution composed of metronidazole, ciprofloxacin and neomycin
Serial Endoscopic SurveillanceProcedure or surgery
Also called SES
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.
SalineDrug
Also called 0.9% saline solution
During endoscopies after imaging, the anastomosis will be lavaged with a placebo direct topical saline solution
| Study group | Role | What they receive |
|---|---|---|
| Cipro, metronidazole, neomycin combo | Experimental | 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. Receives: Drug: Cipro, metronidazole, neomycin combo; Procedure: Serial Endoscopic Surveillance |
| Saline | Placebo comparator | 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. Receives: Procedure: Serial Endoscopic Surveillance; Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Anastomotic Healing Score (ordinal scale ranging from 0 to a maximum of 18)
Measured: Post-operative day 12-28
Secondary outcomes (2)
Anastomotic Healing Score (ordinal scale ranging from 0 to a maximum of 18)
Measured: Post-operative day 0
Anastomotic Healing Score (ordinal scale ranging from 0 to a maximum of 18)
Measured: Post-operative day 3-7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2016 (estimated)
- Study start3 Mar 2017
- Primary completion3 Mar 2017
- Study completion3 Mar 2017
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Anastomotic LeakStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John C Alverdy, MD, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02682485
- Sponsor's protocol ID
- IRB15-0971
- Acronym
- SES-DTA
- Status last verified
- Apr 2023
- First submitted
- 8 Feb 2016
- Last updated
- 26 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Olivas AD, Shogan BD, Valuckaite V, Zaborin A, Belogortseva N, Musch M, Meyer F, Trimble WL, An G, Gilbert J, Zaborina O, Alverdy JC. Intestinal tissues induce an SNP mutation in Pseudomonas aeruginosa that enhances its virulence: possible role in anastomotic leak. PLoS One. 2012;7(8):e44326. doi: 10.1371/journal.pone.0044326. Epub 2012 Aug 31.
PubMed 22952955Shogan BD, Belogortseva N, Luong PM, Zaborin A, Lax S, Bethel C, Ward M, Muldoon JP, Singer M, An G, Umanskiy K, Konda V, Shakhsheer B, Luo J, Klabbers R, Hancock LE, Gilbert J, Zaborina O, Alverdy JC. Collagen degradation and MMP9 activation by Enterococcus faecalis contribute to intestinal anastomotic leak. Sci Transl Med. 2015 May 6;7(286):286ra68. doi: 10.1126/scitranslmed.3010658.
PubMed 25947163
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02682485
- Acronym / sponsor ID
- SES-DTA / IRB15-0971
- Conditions
- Anastomotic Leak, Rectal Cancer
- Keywords
- Rectal Cancer, low anterior resection, SES, SES-DTA, anastomotic leak, anastomotic healing, intestinal healing, anastomosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Study start
- 3 Mar 2017 (actual)
- Primary completion
- 3 Mar 2017 (actual)
- Study completion
- 3 Mar 2017 (actual)
- First posted
- 15 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cipro, metronidazole, neomycin combo | Experimental | Drug: Cipro, metronidazole, neomycin combo, Procedure: Serial Endoscopic SurveillanceAs 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. |
| Saline | Placebo comparator | Procedure: Serial Endoscopic Surveillance, Drug: SalineAs 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cipro, metronidazole, neomycin comboAlso: Cipro/CiproXR/CiproIV; Flagyl/FlagylER/Metro; NeomycinDuring endoscopies after imaging, the anastomosis will be lavaged with an antibiotic solution composed of metronidazole, ciprofloxacin and neomycin | Drug | Cipro, metronidazole, neomycin combo |
| Serial Endoscopic SurveillanceAlso: SESPatients 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. | Procedure or surgery | Cipro, metronidazole, neomycin combo, Saline |
| SalineAlso: 0.9% saline solutionDuring endoscopies after imaging, the anastomosis will be lavaged with a placebo direct topical saline solution | Drug | Saline |
Primary outcome
Anastomotic Healing Score (ordinal scale ranging from 0 to a maximum of 18)
Time frame: Post-operative day 12-28
2 secondary outcomes
Anastomotic Healing Score (ordinal scale ranging from 0 to a maximum of 18)
Time frame: Post-operative day 0
Anastomotic Healing Score (ordinal scale ranging from 0 to a maximum of 18)
Time frame: Post-operative day 3-7
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2023.
- Background: PubMed 22952955Olivas AD, Shogan BD, Valuckaite V, Zaborin A, Belogortseva N, Musch M, Meyer F, Trimble WL, An G, Gilbert J, Zaborina O, Alverdy JC. Intestinal tissues induce an SNP mutation in Pseudomonas aeruginosa that enhances its virulence: possible role in anastomotic leak. PLoS One. 2012;7(8):e44326. doi: 10.1371/journal.pone.0044326. Epub 2012 Aug 31.
- Background: PubMed 25947163Shogan BD, Belogortseva N, Luong PM, Zaborin A, Lax S, Bethel C, Ward M, Muldoon JP, Singer M, An G, Umanskiy K, Konda V, Shakhsheer B, Luo J, Klabbers R, Hancock LE, Gilbert J, Zaborina O, Alverdy JC. Collagen degradation and MMP9 activation by Enterococcus faecalis contribute to intestinal anastomotic leak. Sci Transl Med. 2015 May 6;7(286):286ra68. doi: 10.1126/scitranslmed.3010658.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John C Alverdy, MD principal investigator
University of Chicago
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cipro, metronidazole, neomycin combo, Serial Endoscopic Surveillance and Saline in people with Anastomotic Leak and Rectal Cancer, run by University of Chicago.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 26 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Anastomotic Healing Score (ordinal scale ranging from 0 to a maximum of 18) (time frame: Post-operative day 12-28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02682485, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2023; AzTrials last refreshed its copy on 7 Nov 2026.