The Effect of Higher Protein Dosing in Critically Ill Patients: A Multicenter Registry-Based Randomized Trial: The...

Current randomized trials and observational studies evaluating higher versus lower protein doses in critically ill patients yield inconclusive results. Because of few studies and methodologic limitations, clinical guidelines suggest a wide range of protein intake based on weak evidence. Clinical equipoise about protein dosing exists. The purpose of the current manuscript is to provide the rationale and protocol for a randomized controlled trial (RCT) of 4000 critically ill patients randomly allocated to receive a higher or lower protein dose. We propose a global, volunteer-driven, registry-based RCT involving >100 intensive care units (ICUs). We will enroll mechanically ventilated patients with high nutrition risk, identified by low (≤25) or high (≥35) body mass index, moderate to severe malnutrition, frailty, sarcopenia, or when >96-hour duration of mechanical ventilation is expected. Exclusion criteria include patients who are >96 hours since initiation of mechanical ventilation, moribund, or pregnant, and where the clinician lacks clinical equipoise regarding protein dose. The intervention consists of higher (≥2.2 g/kg/d) or lower (≤1.2 g/kg/d) protein dose, achieved by enteral nutrition, parenteral nutrition, or both. The primary outcome will be 60-day mortality. Key secondary outcomes include time-to-discharge alive from hospital, ICU and hospital survival, and length of stay. As this is research based on existing medical practice, we will apply for a waiver of informed consent, where possible. The large sample size is a reflection of the small signal we expect to see in this large, pragmatic trial.