Intestinal Lavage for the Treatment of Severe C. Difficile Infections

NCT02466698 | Unknown Phase 2

• 1 other identifier: 106184
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Clostridium Difficile infections (CDIs) are treated initially with antibiotic therapy and supportive care, with surgical intervention reserved for patients with significant systemic toxicity or perforation. Severe CDI may be refractory to medical management and require surgical intervention, carrying a mortality of approximately 40%. Mortality associated with CDI increases significantly as the severity of the infection increases. In patients failing medical management, earlier operation is associated with decreased mortality. However, the lack of validated tools to predict the necessity for surgical intervention, combined with the significant morbidity associated with total colectomy significantly reduces the likelihood of patients receiving early surgical intervention. The purpose of the proposed study is to assess the addition of intestinal PEG lavage via nasojejunal tube to usual care in the treatment of adult patients with severe CDI who have no immediate indication for surgical intervention.

Conditions

Clostridium Difficile

Keywords

Colectomy; Surgical Procedures, Operative

Outcome Measures

Primary Outcomes (1)

• Number of eligible participants recruited into the study

  Recruited participants

  12 months

Secondary Outcomes (8)

• Number of participants meeting study inclusion criteria

  12 months

• Number of participants who complete the assigned study protocol

  12 months

• Number of participants who complete the treatment protocol without an adverse event

  12 months

• Number of participants with a complication or adverse event

  12 months

• Number of participants who require initiation of mechanical ventilation following protocol initiation

  12 months

Study Arms (2)

Intestinal Lavage

EXPERIMENTAL

A nasojejunal tube and fecal management system will be inserted. Intestinal lavage with PEG is initiated and increased to a goal rate of 400cc/hour to a total of 8L of PEG. In the absence of an ileus, lavage should be initiated at 200cc/hr. Tolerance is confirmed if the rectal effluent volume is ≥50% of the lavage volume over the first 6 hours and no emesis has developed. If the consulting surgical service suspects a significant ileus, the lavage is initiated at 100cc/hr. If tolerance is confirmed the lavage rate is increased in a stepwise fashion. Antibiotic regimen will consist of Vancomycin 500mg via nasojejunal every 6 hours and Metronidazole 500 mg IV three times daily for 14 days. PEG will be held for 2 hours after administration of Vancomycin.

Procedure: Intestinal Lavage; Drug: Vancomycin; Drug: PEG; Drug: Metronidazole

Usual Care

ACTIVE COMPARATOR

Patients will receive usual care for severe CDI. This includes an antibiotic regimen of Vancomycin 500mg orally every 6 hours and Metronidazole 500mg IV three times daily for 14 days. The usual care group will receive the same antibiotic doses as the experimental arm of the study. For both arms, indications to escalate treatment to surgical intervention will ultimately be based on the clinical assessment by the surgical service. An absolute indication for surgery is perforation. Other indications such as toxic megacolon, worsening peritonitis or biochemical profile lavage are relative indications that vary according to clinician and individual patient characteristics.

Drug: Vancomycin; Drug: Metronidazole

Interventions

Intestinal Lavage PROCEDURE

A nasojejunal tube and fecal management system will be inserted. Intestinal lavage with PEG is initiated and increased to a goal rate of 400cc/hour to a total of 8L of PEG. In the absence of an ileus, lavage should be initiated at 200cc/hr. Tolerance is confirmed if the rectal effluent volume is ≥50% of the lavage volume over the first 6 hours and no emesis has developed. If the consulting surgical service suspects a significant ileus, the lavage is initiated at 100cc/hr. If tolerance is confirmed the lavage rate is increased in a stepwise fashion. Antibiotic regimen will consist of Vancomycin 500mg via nasojejunal every 6 hours and Metronidazole 500 mg IV three times daily for 14 days. PEG will be held for 2 hours after administration of Vancomycin.

Also known as: PEG Lavage

Intestinal Lavage

Vancomycin DRUG

Patients will receive standard antibiotic treatment for severe CDI. This includes an antibiotic regimen of Vancomycin 500mg orally every 6 hours and Metronidazole 500mg IV three times daily for 14 days. The standard medical care group (active comparator group) will receive the same antibiotic doses as the experimental arm of the study For both arms, indications to escalate treatment to surgical intervention will ultimately be based on the clinical assessment by the surgical service. An absolute indication for surgery is perforation. Other indications such as toxic megacolon, worsening peritonitis or biochemical profile lavage are relative indications that vary according to clinician and individual patient characteristics.

Also known as: Antibiotic-V

Intestinal Lavage; Usual Care

PEG DRUG

Polyethylene glycol 3350, 8L in 48 hours, via a nasojejunal tube will be used to facilitate intestinal lavage.

Also known as: Polyethylene glycol 3350

Intestinal Lavage

Metronidazole DRUG

Patients will receive standard antibiotic treatment for severe CDI. This includes an antibiotic regimen of Vancomycin 500mg orally every 6 hours and Metronidazole 500mg IV three times daily for 14 days. The standard medical care group (active comparator group) will receive the same antibiotic doses as the experimental arm of the study For both arms, indications to escalate treatment to surgical intervention will ultimately be based on the clinical assessment by the surgical service. An absolute indication for surgery is perforation. Other indications such as toxic megacolon, worsening peritonitis or biochemical profile lavage are relative indications that vary according to clinician and individual patient characteristics.

Also known as: Antibiotic-M

Intestinal Lavage; Usual Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult (\>= 18 years) inpatients at LHSC with symptomatic CDI (diarrhea or colonic ileus)
• CDI confirmed by standard hospital microbiology lab testing
• Patients must meet criteria for severe CDI, defined as either: white blood cell \> 15,000 or Serum Creatinine \> 1.5 times the pre-morbid level
• Patients must have at least one additional risk factor for severity:
• i. Fever \>38.5 (if no other source of fever suspected) ii. Vasopressor requirement iii. Mechanical ventilation requirement iv. Serum lactate \>5 mmol/L v. Colonic distension (\>6cm transverse colon diameter on abdominal Xray or CT) vi. Colonic wall thickening, on abdominal Xray or CT, as reported by radiology. vii. Calculated ATLAS score ≥ 4

You may not qualify if:

• The patient is deemed to have an immediate indication for surgery related to the diagnosis of CDI by the on call General Surgery service.
• Pre-existing bowel discontinuity (e.g. ileostomy).
• General Surgery service or most responsible care team deem the patient to have a contraindication to nasojejunal tube or fecal management system
• Patients anticipated to be intolerant of the study regimen (e.g. severe ileus, unable to tolerate oral intake, etc.)

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead
• London Health Sciences Centre: collaborator

Study Sites (1)

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

RECRUITING

Related Publications (1)

• McCreery G, Jones PM, Kidane B, DeMelo V, Mele T; ERASE C. difficile (Early Rescue from Acute SEvere Clostridium difficile) Trials Group. Polyethylene glycol intestinal lavage in addition to usual antibiotic treatment for severe Clostridium difficile colitis: a randomised controlled pilot study. BMJ Open. 2017 Jul 31;7(7):e016803. doi: 10.1136/bmjopen-2017-016803.

  PMID: 28760801 DERIVED

MeSH Terms

Interventions

polyethylene glycol 3350; Vancomycin; Metronidazole

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Tina E Mele, MD PhD

  London Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tina E Mele, MD PhD

CONTACT

519-663-3970; tina.mele@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 4, 2015
• First Posted: June 9, 2015
• Study Start: August 1, 2016
• Primary Completion: August 1, 2019
• Study Completion: August 1, 2019
• Last Updated: August 13, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be available for sharing after publishing the study.
• Access Criteria: A direct request from PI.

Locations

CA (1)