Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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: NCT02389036
Recruitment Status : Recruiting
First Posted : March 17, 2015
Last Update Posted : December 28, 2020
Sponsor:
Collaborators:
Imperial College London
Sunnybrook Health Sciences Centre
Information provided by (Responsible Party):
The George Institute

Tracking Information
First Submitted Date  ICMJE March 2, 2015
First Posted Date  ICMJE March 17, 2015
Last Update Posted Date December 28, 2020
Actual Study Start Date  ICMJE May 1, 2017
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 9, 2015)
Hospital Mortality [ Time Frame: Hospital discharge [up to 6 months after randomization ]
all-cause mortality at time of hospital discharge
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2017)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: March 9, 2015)
  • The incidence of antibiotic resistant organisms [ Time Frame: Data is collected at the time of ICU admission ]
    The incidence of antibiotic resistant organisms isolated from clinical and surveillance specimens per 1000 patient admissions.
  • The cost-effectiveness of the systematic delivery of SDD [ Time Frame: Over 6 months after hospital admission ]
    The cost-effectiveness of the systematic delivery of SDD as measured over 6 months after ICU admission and with a modelled lifetime horizon from the healthcare payer perspective.
  • Long term mortality [ Time Frame: 90 days and 6 months after site randomization ]
    3 and 6 months mortality data will be collected in patients eligible, consented and enrolled into the SuDDICU-cost-effectiveness study
  • Quality of life Assessment [ Time Frame: 6 months after site randomization ]
    After 6 month post- randomisation quality of life in patients eligible, consented and enrolled into the SuDDICU-cost-effectiveness study
  • Total antibiotic usage [ Time Frame: during ICU admission ]
    Total antibiotic usage (as days of therapy) during ICU admission in all ICU admissions per 1000 patient 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 per 1000 patient 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 per 1000 patient 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 per 1000 patient admissions
  • Changes in antibiotic resistance rates between study epochs (pre-trial, trial and post-trial) within groups [ Time Frame: Through out all study periods ]
    Changes in ARO rates between time epochs (pre-trial, trial 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Selective Decontamination of the Digestive Tract in Intensive Care Unit Patients
Official Title  ICMJE A Crossover, Cluster Randomised Controlled Trial of Selective Decontamination of the Digestive Tract in Intensive Care Unit Patients (SuDDICU)
Brief Summary

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 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.

Detailed Description

Design- international, 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 ICU patients during one week of each month during the 3-month surveillance period before the first intervention period; in all trial eligible patients during the two 12-month intervention periods; in all ICU patients during one week of each month of the final 3-months of the two intervention periods; in all ICU patients during one week of each month during the 3-month inter-period and post-trial periods.

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.

All patients eligible for the intervention will receive the following in addition to the usual infection control measures:

  1. 1. A six-hourly topical application of 0.5g paste, containing colistin 10mg, tobramycin 10mg and nystatin 125,000 IU, 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 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 (e.g. allergy). Patients already receiving an alternative IV antibiotic to treat infection will not receive this additional IV antibiotic, but will continue the prescribed antibiotic for the usual duration of therapy.

Statistical considerations and sample size- SuDDICU will recruit 10 000 to 15 000 patients from 29 ICUs and will have 80% power to detect an absolute reduction in hospital mortality of 3-5% from a baseline mortality of 29%, depending on the precise number of clusters.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Critical Illness
  • Sepsis
  • Septic Shock
  • Ventilator Associated Pneumonia
Intervention  ICMJE
  • Drug: SDD Oral Paste
    A six-hourly topical application of 0.5g paste, containing colistin 10mg, tobramycin 10mg and nystatin 125,000 IU, to the buccal mucosa and oropharynx
    Other Name: Colistin, Tobramycin and Nystatin
  • Drug: SDD Gastric Suspension
    2. A six-hourly administration of 10 mL of a suspension containing 100 mg colistin, 80 mg tobramycin and 2 x 10 ^6 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: Ceftriaxone, Cefotaxime or Ciprofloxacin
Study Arms  ICMJE
  • No Intervention: Control group- standard care
    Standard care- In Australia 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. A six-hourly topical application of 0.5g paste, containing colistin 10mg, tobramycin 10mg and nystatin 125,000 IU, 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 10^6 IU nystatin, to the gastrointestinal tract via a gastric/post-pyloric tube
    3. A four-day course of an 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 (e.g. allergy). Patients already receiving an alternative IV antibiotic to treat infection will not receive this additional IV antibiotic, but will continue the prescribed antibiotic for the usual duration of therapy.
    Interventions:
    • Drug: SDD Oral Paste
    • Drug: SDD Gastric Suspension
    • Drug: Intravenous Antibiotic
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 23, 2020)
15000
Original Estimated Enrollment  ICMJE
 (submitted: March 9, 2015)
24000
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 the UK
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE Australia,   Canada,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02389036
Other Study ID Numbers  ICMJE GI-CCT070115
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The protocol and statistical analysis plan will be made public in 2020. The participant level dataset will not be publicly available immediately but will be available to collaborative researchers after consultation and negotiation with the SuDDICU Investigators.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: The SuDDICU Protocol V4.0 and SAP V1.0 are available on the open science framework in pre print.
Access Criteria: Public access, no access criteria to view the SuDDICU Protocol V4.0 and SAP V1.0
URL: https://osf.io/
Responsible Party The George Institute
Study Sponsor  ICMJE The George Institute
Collaborators  ICMJE
  • Imperial College London
  • Sunnybrook Health Sciences Centre
Investigators  ICMJE
Study Chair: John Myburgh, MBBCh PhD The George Institute
Study Chair: Brian Cuthbertson, MD FRCA Sunnybrook Health Sciences Centre
Study Chair: Anthony Gordon, MD FRCA Imperial College London
PRS Account The George Institute
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP