A major clinical trial investigating the impact of increased protein delivery in critically ill patients is currently underway across intensive care units in Australia and New Zealand. The TARGET Protein trial employs an innovative cluster randomized, cross-over design to evaluate whether augmented protein delivery through enteral nutrition improves patient outcomes.
Trial Design and Implementation
The study involves eight ICUs alternating between two different enteral nutrition formulas over four 3-month periods. Four ICUs begin with the augmented protein formula while the other four start with standard protein formula, then cross over every three months. This design helps control for period effects while maximizing statistical power.
Eligible patients must be at least 16 years old and requiring enteral nutrition during their ICU stay. The trial excludes patients for whom the formula is contraindicated, those who received more than 12 hours of non-trial formula, or previous trial participants.
Intervention Details
During intervention periods, patients receive Nutrison Protein Intense® containing 100g protein and 1,260 kcal per 1000ml. The control periods utilize Nutrison Protein Plus® with 63g protein and 1,250 kcal per 1000ml. This pragmatic approach allows for evaluation of different protein levels while maintaining similar caloric content.
Primary and Secondary Outcomes
The trial's primary outcome measure is the number of days free of the index hospital and alive at day 90 - a composite endpoint capturing both survival and recovery. Secondary outcomes include:
- Hospital-free days among survivors
- 90-day mortality
- Duration of mechanical ventilation
- ICU and hospital length of stay
- Incidence of tracheostomy
- Need for new renal replacement therapy
Statistical Considerations and Data Collection
With a planned enrollment of approximately 3,000 patients, the trial is powered to detect a one-day difference in hospital-free days. Data collection leverages the existing Australian New Zealand Intensive Care Society Adult Patient Database, with additional mortality data obtained through national death registries.
Clinical Significance
This trial addresses a crucial question in critical care nutrition - whether higher protein delivery can improve patient outcomes. The pragmatic design using existing clinical databases and routine care processes enhances the trial's real-world applicability. Results could significantly influence nutritional practices in intensive care units worldwide.
The study team has carefully considered potential confounders and implemented robust statistical methods to account for the cluster cross-over design. This includes sophisticated approaches to handling missing data and pre-planned subgroup analyses for key patient populations such as elderly patients, those with high BMI, and those requiring renal replacement therapy.
