A crossover, cluster randomised controlled trial of Selective Decontamination of the Digestive Tract in Intensive Care Unit patients (SuDDICU)

Sepsis is the most common cause of death in critically ill patients, with a quarter of those who develop severe sepsis dying during their hospitalisation. While many patients are admitted to hospital with severe sepsis, others will develop sepsis while in the hospital. These hospital-acquired infections are recognised as an increasing public health problem, causing more than one million deaths annually worldwide.

Hospital-acquired infection is also associated with increased hospital admission time and associated health-care costs. The prevention of ICU-acquired sepsis is therefore critical, and the subject of a number of infection control protocols and patient safety initiatives including ‘bundles of care’ aimed at reducing catheter-related bloodstream infections, ventilator-associated pneumonia, and infections from antibiotic resistant microorganisms. Selective decontamination of the digestive tract (SDD) is an infection control approach designed to reduce mortality through preventing sepsis, but the balance of risks associated with the use of SDD remains controversial.

Design

An international, multicentre, crossover, cluster RCT (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 interventional 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 interventional periods; in all ICU patients during one week of each month during the 3-month inter-period and post-trial periods.

SuDDICU will recruit 10 000-15 000 patients across 40-50 ICUs in Australia, UK and Canada.

Study outcomes

The primary outcomes aims to determine if the systematic delivery of SDD to critically ill patients within an ICU reduces hospital mortality.

Secondary ecology outcomes will be assessed to determine the following:

The effect of SDD on the incidence of antibiotic resistant organisms (AROs) isolated from clinical and surveillance specimens in those ICUs
Changes in ARO rates between surveillance, intervention and post intervention periods.
The incidence of Clostridium difficile infections
Total antibiotic usage
Duration of mechanical ventilation
ICU length of stay
ICU mortality
Hospital length of stay
Health economic analysis from a healthcare system perspective

Methods

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

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.
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.
A four-day course of an intravenous 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 intravenous antibiotic to treat infection will not receive this additional intravenous antibiotic, but will continue the prescribed antibiotic for the usual duration of therapy.

Status

The SuDDICU collaboration is an international, investigator-initiated research collaboration that was established through research networks in Australia, New Zealand, Canada and the UK in 2009 with the aim of addressing the controversy about the role of SDD in intensive care practice.

The international SuDDICU research program consists of six phases:

Systematic review of the literature (completed)
Exploratory study of risks, benefits, and barriers to the use of SDD (completed)
Inception cohort pilot study (completed)
Cluster crossover randomised controlled trial (x-cRCT) with ecological and health economic evaluations (the protocol for this study)
Knowledge translation / implementation study (to be completed)
Post-implementation surveillance of effectiveness and antibiotic resistance pattern study (to be completed).