Selective Decontamination of the Digestive Tract in Intensive Care Unit Patients

NCT02389036 | Completed Phase 3 DMC

• 1 other identifier: GI-CCT070115
• Study Type: interventional
• Target: 20,010
• Locations: 3 countries
• Sites: 3

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.

Conditions

Critical Illness; Sepsis; Septic Shock; Ventilator Associated Pneumonia

Outcome Measures

Primary Outcomes (1)

• Hospital Mortality

  all-cause mortality at time of hospital discharge

  Hospital discharge [up to Day 90 after randomization]

Secondary Outcomes (9)

• Total antibiotic usage

  during ICU admission

• The incidence of antibiotic resistant organisms in cultures from blood or other sterile sites

  during ICU admission

• The incidence of antibiotic-resistant organism in non-sterile clinical and surveillance specimens

  during ICU admission

• The incidence of C. difficile infections

  during ICU admission

• Changes in antibiotic resistance rates between study epochs (pre-trial, interperiod gap and post-trial) within groups

  Through out all study periods

Study Arms (2)

Control group- standard care

NO INTERVENTION

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.

SDD intervention group

EXPERIMENTAL

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.

Drug: SDD Oral Paste; Drug: SDD Gastric Suspension; Drug: Intravenous Antibiotic

Interventions

SDD Oral Paste DRUG

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

Also known as: Colistin, Tobramycin and Nystatin

SDD intervention group

SDD Gastric Suspension DRUG

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

Also known as: Colistin, Tobramycin and Nystatin

SDD intervention group

Intravenous Antibiotic DRUG

A four-day course of an intravenous antibiotic in patients not already receiving a therapeutic antibiotic

Also known as: Ceftriaxone, Cefotaxime or Ciprofloxacin

SDD intervention group

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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.

You may not qualify if:

• Unwilling or unable to follow trial protocols.
• Unable to capture the minimum data set required for the study.
• 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
• Specialty paediatric ICUs
• Patients enrolled in a trial that would interact with the intervention
• Patients with a known allergy, sensitivity or interaction to trial topical intervention drugs
• Patients who are known or suspected to be pregnant
• Patients who are moribund and not expected to survive the next 12 hours
• Patients less than 16 years of age will not be enrolled in the UK

Sponsors & Collaborators

• The George Institute: lead
• Imperial College London: collaborator
• Sunnybrook Health Sciences Centre: collaborator

Study Sites (3)

The George Institute for Global Health

Sydney, New South Wales, 2000, Australia

Location

Sunnybrook Health Sciences Centre

Toronto, M4N 3M5, Canada

Location

Imperial College London

London, W21PG, United Kingdom

Location

Related Publications (7)

• Cuthbertson BH, Campbell MK, MacLennan G, Duncan EM, Marshall AP, Wells EC, Prior ME, Todd L, Rose L, Seppelt IM, Bellingan G, Francis JJ. Clinical stakeholders' opinions on the use of selective decontamination of the digestive tract in critically ill patients in intensive care units: an international Delphi study. Crit Care. 2013 Nov 8;17(6):R266. doi: 10.1186/cc13096.

  PMID: 24207137 RESULT

• Daneman N, Sarwar S, Fowler RA, Cuthbertson BH; SuDDICU Canadian Study Group. Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis. Lancet Infect Dis. 2013 Apr;13(4):328-41. doi: 10.1016/S1473-3099(12)70322-5. Epub 2013 Jan 25.

  PMID: 23352693 RESULT

• Cuthbertson BH, Francis J, Campbell MK, MacIntyre L, Seppelt I, Grimshaw J; SuDDICU study groups. A study of the perceived risks, benefits and barriers to the use of SDD in adult critical care units (the SuDDICU study). Trials. 2010 Dec 3;11:117. doi: 10.1186/1745-6215-11-117.

  PMID: 21129208 RESULT

• SuDDICU Investigators for the Australia and New Zealand Intensive Care Society Clinical Trials Group and the Canadian Critical Care Trials Group; Cuthbertson BH, Billot L, Campbell MK, Daneman N, Davis JS, Delaney A, Devaux A, Ferguson ND, Finfer SR, Fowler R, Gordon AC, Hammond NE, Klein G, Li Q, Marshall J, Micallef S, Murthy S, Mysore J, Naik C, Patel C, Pinto R, Rose L, Seppelt IM, Venkatesh B, Young PJ, Myburgh JA. Selective Decontamination of the Digestive Tract during Ventilation in the ICU. N Engl J Med. 2025 Oct 29. doi: 10.1056/NEJMoa2506398. Online ahead of print.

  PMID: 41159880 DERIVED

• Billot L, Cuthbertson B, Gordon A, Al-Beidh F, Correa M, Davis J, Finfer S, Glass P, Goodman F, Hammond N, Iredell J, Miller J, Murthy S, Rose L, Seppelt I, Taylor C, Young P, Myburgh J; SuDDICU Investigators. Protocol summary and statistical analysis plan for the Selective Decontamination of the Digestive Tract in Intensive Care Unit Patients (SuDDICU) crossover, cluster randomised controlled trial. Crit Care Resusc. 2023 Oct 18;23(2):183-193. doi: 10.51893/2021.2.oa5. eCollection 2021 Jun.

  PMID: 38045525 DERIVED

• Young PJ, Devaux A, Li Q, Billot L, Davis JS, Delaney A, Finfer SR, Hammond NE, Micallef S, Seppelt IM, Venkatesh B, Myburgh JA; SuDDICU Australia Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Selective digestive tract decontamination in critically ill adults with acute brain injuries: a post hoc analysis of a randomized clinical trial. Intensive Care Med. 2024 Jan;50(1):56-67. doi: 10.1007/s00134-023-07261-y. Epub 2023 Nov 20.

  PMID: 37982826 DERIVED

• SuDDICU Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group; Myburgh JA, Seppelt IM, Goodman F, Billot L, Correa M, Davis JS, Gordon AC, Hammond NE, Iredell J, Li Q, Micallef S, Miller J, Mysore J, Taylor C, Young PJ, Cuthbertson BH, Finfer SR. Effect of Selective Decontamination of the Digestive Tract on Hospital Mortality in Critically Ill Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial. JAMA. 2022 Nov 15;328(19):1911-1921. doi: 10.1001/jama.2022.17927.

  PMID: 36286097 DERIVED

MeSH Terms

Conditions

Critical Illness; Sepsis; Shock, Septic; Pneumonia, Ventilator-Associated

Interventions

Colistin; Tobramycin; Nystatin; Ceftriaxone; Cefotaxime; Ciprofloxacin

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Healthcare-Associated Pneumonia; Cross Infection; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease

Intervention Hierarchy (Ancestors)

Polymyxins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Antimicrobial Cationic Peptides; Peptides; Amino Acids, Peptides, and Proteins; Antimicrobial Peptides; Pore Forming Cytotoxic Proteins; Membrane Proteins; Proteins; Nebramycin; Kanamycin; Aminoglycosides; Glycosides; Carbohydrates; Macrolides; Lactones; Organic Chemicals; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines

Study Officials

• 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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Cluster, crossover, randomized clinical trial

Study Record Dates

• First Submitted: March 2, 2015
• First Posted: March 17, 2015
• Study Start: May 1, 2017
• Primary Completion: April 26, 2023
• Study Completion: April 26, 2023
• Last Updated: August 14, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The SuDDICU Protocol V4.0 and SAP V1.1 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 V1.1

Locations

CA (1); GB (1); AU (1)