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Selective Decontamination of the Digestive Tract in Intensive Care Unit Patients (SuDDICU-ANZ)

This study is currently recruiting participants.
Verified September 2017 by The George Institute
Sponsor:
ClinicalTrials.gov Identifier:
NCT02389036
First Posted: March 17, 2015
Last Update Posted: September 8, 2017
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.
Collaborator:
Medical Research Institute of New Zealand
Information provided by (Responsible Party):
The George Institute
  Purpose

Introduction- Hospital acquired infections (HAI) are a major cause of morbidity and mortality and increase health care costs. Critically ill patients are particularly susceptible to these infections and have an even higher mortality. One intervention that has gained much interest in the medical literature for reducing infection rates and deaths from HAIs is selective decontamination of the digestive tract (SDD). SDD involves the application of antibiotic paste to the mouth, throat, stomach and a short course of intravenous antibiotics. The evidence supporting the use of SDD for saving lives and preventing infections is actually quite strong. However, health care professionals in many parts of the world have refrained from using SDD due to fears of the effects of overuse of antibiotics on the frequency of infections with resistant bacteria such as multi-resistant Gram negative organisms, MRSA and Clostridium difficile.

SuDDICU-ANZ is a cross-over, cluster randomised trial comparing the effect of using selective decontamination of the digestive tract (SDD) plus standard care, to standard care alone on hospital mortality in patients receiving mechanical ventilation in the intensive care unit (ICU).

Secondary outcomes include an ecological assessment and a long-term health economic analysis.


Condition Intervention Phase
Critical Illness Sepsis Septic Shock Ventilator Associated Pneumonia Drug: SDD Paste Drug: SDD Suspension Drug: Intravenous Antibiotic Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Crossover, Cluster Randomised Controlled Trial of Selective Decontamination of the Digestive Tract in Intensive Care Unit Patients in Australian and New Zealand (SuDDICU-ANZ)

Further study details as provided by The George Institute:

Primary Outcome Measures:
  • Hospital Mortality [ Time Frame: Hospital discharge [up to 6 months after randomization ]
    all-cause mortality at time of hospital discharge


Secondary Outcome Measures:
  • Total antibiotic usage [ Time Frame: during ICU admission ]
    Total antibiotic usage (as daily defined doses) during ICU admission in all ICU admissions.

  • The incidence of antibiotic resistant organisms in cultures from blood or other sterile sites [ Time Frame: during ICU admission ]
    The incidence of antibiotic resistant organisms in cultures from blood or other sterile sites during ICU admission in all ICU admissions.

  • The incidence of antibiotic-resistant organism in non-sterile clinical and surveillance specimens [ Time Frame: during ICU admission ]
    The incidence of antibiotic-resistant organism in non-sterile clinical and surveillance specimens during ICU admission in all ICU admissions

  • The incidence of C. difficile infections [ Time Frame: during ICU admission ]
    The incidence of C. difficile infections during ICU admission in all ICU admissions

  • Changes in antibiotic resistance rates between study epochs (pre-trial, interperiod gap and post-trial) within groups [ Time Frame: Through out all study periods ]
    Changes in ARO rates between time epochs (pre-trial, trial, inter-period gap and post-trial) within groups. With control group data to give the secular trend in ARO with time and SDD group data studying the effects of SDD withdrawal from practice in the year after SDD delivery

  • Duration of mechanical ventilation [ Time Frame: Time of enrolment to ICU discharge within index hospital admission, assessed up to 12 months ]
    Duration that the patient is mechanically ventilated in the ICU

  • ICU length of stay [ Time Frame: From the time of enrolment to ICU discharge, assessed up to 12 months ]
    The length of time a patient stays in the ICU

  • Hospital length of stay [ Time Frame: From time of enrolment to hospital discharge within the index hospital admission, assessed up to 12 months ]
    The total hospital length of stay for patient


Estimated Enrollment: 8000
Actual Study Start Date: May 1, 2017
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: October 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Control group- standard care
Standard care- In Australia and New Zealand there are no national guidelines so local policy is determined by each ICU. We are recommending (but not mandating) that control and SDD group management be in line with these national guidelines. We will recommend control and SDD group management is in line with current national standards of practice that may or may not include a VAP bundle. We will monitor record data regarding the nature and delivery of the control and SDD group co-interventions.
Experimental: SDD intervention group

The intervention will entail:

  1. SDD paste: The six-hourly topical application of 0.5g paste, containing colistin 2%, tobramycin 2% and nystatin 2%, to the buccal mucosa and oropharynx.
  2. SDD suspension: The six-hourly administration of 10 mls suspension containing 100 mg colistin/ polymixin, 80 mg tobramycin and 2 x 106 IU nystatin, to the gastrointestinal tract via the gastric / jejunal tube.
  3. A four-day course of an intravenous antibiotic in patients not already receiving a therapeutic antibiotic
Drug: SDD Paste
A six-hourly topical application of 0.5g paste, containing colistin 2%, tobramycin 2% and nystatin 2%,
Other Name: Colistin, Tobramycin and Nystatin
Drug: SDD Suspension
A six-hourly administration of 10 ml of a suspension containing 100 mg colistin, 80 mg tobramycin and 2 x 106 IU nystatin, to the gastrointestinal tract via a gastric/post-pyloric tube
Other Name: Colistin, Tobramycin and Nystatin
Drug: Intravenous Antibiotic
A four-day course of an intravenous antibiotic in patients not already receiving a therapeutic antibiotic
Other Name: Cefotaxime or Ciprofloxacin

Detailed Description:

Design- A bi-national, multicentre, crossover, cluster randomised controlled trial (x-cRCT) of eligible patients in participating ICUs using two 12-month interventional trial periods separated by a 3-month inter-period gap.

An observational ecological assessment will be conducted in all eligible patients during the two 12-month intervention periods and in all patients admitted to participating ICUs during the first week of each month over three 3-month surveillance periods before, during the inter-period gap and after the second 12-month interventional period.

Participants- General ICUs that admit mechanically ventilated patients will be randomised in the first 12-month period to either implement the SDD protocol in addition to standard care or to continue standard care without SDD, and then to cross over to the other arm during the second 12-month period.

Eligible patients are defined as:

  1. All patients who are mechanically ventilated via an endotracheal tube on admission to the ICU and who are predicted to remain ventilated beyond the end of the calendar day after the day of ICU admission, or
  2. All patients who become mechanically ventilated via an endotracheal tube during their ICU stay and who are predicted to remain ventilated beyond the end of the calendar day after the day they are first ventilated, or
  3. All patients who not already recruited but are receiving mechanical ventilation via an endotracheal tube and are expected to receive ongoing ventilation for a further 48-hours or more despite an earlier prediction that ventilation would be discontinued earlier.

Intervention- In the SDD arm, all eligible patients will receive:

  1. A six-hourly topical application of 0.5g paste containing colistin 2%, tobramycin 2% and nystatin 2%, to the buccal mucosa and oropharynx
  2. A six-hourly administration of 10 mL of a suspension containing 100 mg colistin, 80 mg tobramycin and 2 x 106 IU nystatin, to the gastrointestinal tract via a gastric/post-pyloric tube
  3. A four-day course of an intravenous (IV) antibiotic. Patients not already receiving a therapeutic antibiotic will be prescribed cefotaxime 1g six-hourly or ceftriaxone 1g daily, with dose adjusted as appropriate for organ dysfunction. Ciprofloxacin (400mg 12-hourly) may be used as an alternative if there is a contraindication to cephalosporins, such as allergy. Patients already receiving an alternative IV antibiotic as clinically indicated will not receive an additional IV antibiotic, but will continue the prescribed antibiotic for the usual duration of therapy.

Statistical considerations and sample size- SuDDICU-ANZ will recruit 8,000 patients from 25-30 ICUs and will be able to detect a 3.6-3.7% absolute reduction in hospital mortality from a baseline mortality of 29%, using 80% power, α <0.05.

  Eligibility

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Site inclusion for cluster study- A general ICU or complex of ICUs (medical, surgical, mixed) capable of treating mechanically ventilated critically ill adult patients.

Patient inclusion criteria

  1. All patients who are mechanically ventilated via an endotracheal tube on admission to ICU and who are predicted to remain ventilated beyond the end of the calendar day after the day of ICU admission, or
  2. All patients who become mechanically ventilated via an endotracheal tube during their ICU stay and who are predicted to remain ventilated beyond the end of the calendar day after the day they are first ventilated, or
  3. All patients not already recruited who are receiving mechanical ventilation via an endotracheal tube and are expected to receive ongoing ventilation for a further 48 hours or more despite an earlier prediction that ventilation would be discontinued earlier.

Site exclusion criteria for cluster study-

  1. Unwilling or unable to follow trial protocols.
  2. Unable to capture the minimum data set required for the study.
  3. Isolated specialty ICUs not co-located with a general ICU, such as solely cardiac, neurological/neurosurgical and burns ICUs, but such specialty patients cared for in general ICUs will be included
  4. Specialty paediatric ICUs

Exclusion Criteria:

Patient exclusion criteria

  1. Patients enrolled in a trial that would interact with the intervention
  2. Patients with a known allergy, sensitivity or interaction to trial topical intervention drugs
  3. Patients who are known or suspected to be pregnant
  4. Patients who are moribund and not expected to survive the next 12 hours
  5. Patients less than 16 years of age will not be enrolled in New Zealand
  Contacts and Locations
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): NCT02389036


Contacts
Contact: John Myburgh, MBBCh PhD +61 2 8052 4348 jmyburgh@georgeinstitute.org.au
Contact: Ian Seppelt, MBBS PhD +61 412 595 647 Iseppelt@georgeinstitute.org.au

Locations
Australia, New South Wales
The George Institute for Global Health Recruiting
Sydney, New South Wales, Australia, 2000
Contact: John Myburgh, | MBBCh PhD    61 2 8052 4348    jmyburgh@georgeinstitute.org.au   
Sponsors and Collaborators
The George Institute
Medical Research Institute of New Zealand
Investigators
Study Chair: John Myburgh, MBBCh PhD The George Institute
Study Chair: Brian Cuthbertson, MD FRCA Sunnybrook Health Sciences Centre
  More Information

Publications:
Responsible Party: The George Institute
ClinicalTrials.gov Identifier: NCT02389036     History of Changes
Other Study ID Numbers: GI-CCT070115
First Submitted: March 2, 2015
First Posted: March 17, 2015
Last Update Posted: September 8, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The protocol and statistical analysis plan will be made public in 2017. The participant level dataset will not be publicly available immediately but will be available to collaborative researchers after consultation and negotiation with the SuDDICU- ANZ Investigators.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Pneumonia
Shock, Septic
Critical Illness
Pneumonia, Ventilator-Associated
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Shock
Disease Attributes
Cross Infection
Ventilator-Induced Lung Injury
Lung Injury
Anti-Bacterial Agents
Ciprofloxacin
Tobramycin
Colistin
Nystatin
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents