Clinical trial NCT03170401: Supplemental Enteral Protein in Critical Illness
Official title: Protein-enhanced Enteral Nutrition and Metabolomics in Critically Ill Trauma and Surgical Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Nutrition Disorder
Trauma
Critical Illness
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Institute of General Medical Sciences (NIGMS)
First posted: 2017-05-31
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of this study is too determine the effect of enteral protein supplementation on biochemical measures of inflammation and protein metabolism in critically ill surgical patients. The investigators will also collect data on important clinical outcomes, including infectious complications, duration of mechanical ventilation and other measures of recovery from critical illness.

Hypothesis: That early supplemental protein will increase serum concentrations of transthyretin at three weeks after the onset of illness or injury. Secondarily, the investigators will test whether supplementation, reduces infectious complications and increases ventilator-free days.

Detailed description: Critically ill patients are frequently undernourished. The investigator's observations indicate that surgical and trauma patients who require artificial nutrition are likely to be markedly undernourished during the first week of critical illness, will often require intensive and costly support for organ failure, have prolonged stays in the intensive care unit and extended hospitalizations. Nitrogen deficits are typically greater and receive less attention than caloric deficits. In some respects, the focus on avoiding caloric deficits may have missed the mark. A broader consideration of nutrient needs, such as protein, is required. For instance, there are observational data supporting the notion that protein intake is at least as important as caloric intake in promoting recovery in critical illness. Only recently have national guidelines (ASPEN 2016) begun to specifically address protein requirements (1.5 - 2.0 g/kg/day). For a number of years, the approach to these critically ill patients has included weekly measurements of 24 hour urine nitrogen excretion in order to better understand the protein deficits that develop. Based upon physician preference, the investigators can then use enteral protein supplementation to match the urinary nitrogen excretion in order to achieve net "zero" nitrogen balance. With supplemental protein administration, physicians are able to reduce this deficit and in some cases, generate a positive nitrogen balance. However, there are no data to indicate that this approach (which is included as part of the 2016 ASPEN guidelines) improves clinical outcomes. The most obvious mechanism whereby supplemental protein may influence outcomes by providing more metabolic substrate for protein building. Feeding the gut likely creates a more anabolic environment and additional protein may facilitate anabolism. However, it is not known whether protein supplementation improves markers of anabolism and protein synthesis. In this study, the investigators will measure the anabolic effect of supplemental protein by following serum transthyretin concentrations as part of the standard clinical care.The investigators postulate that supplemental protein will attenuate the drop in comparison to no supplemental protein and will hasten the return to normal concentrations.

The proposed study will test whether early, and standardized protein supplementation: (1) Increases protein delivery during the first 2 weeks after injury, (2) increases serum transthyretin concentrations at 3 weeks after injury (3) increases ventilator-free days.

Study aims:

The aim of this study is to determine the effect of enteral protein supplementation on biochemical measures of protein metabolism in critically ill surgical patients. The investigators will also collect data on important clinical outcomes, including infectious complications, duration of mechanical ventilation and other measures of recovery from critical illness. However, this study will not enroll a sufficient number of subjects to adequately test for differences in these clinical end-points.

Hypothesis: That early supplemental protein will, increase serum concentrations of transthyretin at three weeks after injury. Secondarily, the investigators will test whether supplementation reduces infectious complications and increases ventilator-free days.

Eligibility criteria: Inclusion Criteria:

* Critically ill adult trauma (blunt and penetrating) victims
* Other critically ill surgical patients
* enteral nutrition required during the first 96 hours after injury
* expected to require nutritional support for at least 1 week

Exclusion Criteria:

* Significant chronic organ failure,
* severe malnutrition pre-existing prior to ICU admission
* not expected to survive from their traumatic injuries.
* intestinal discontinuity
* short bowel syndrome
* bowel obstruction
* enterocutaneous fistula
* intestinal ischemia
* massive gastrointestinal hemorrhage
* inability to obtain enteral access.

Primary outcomes:
measure: Serum Concentrations of Transthyretin at 3 Weeks After Injury.
timeFrame: 3 weeks after admission for injury
Secondary outcomes:
measure: Ventilator-free Days.
timeFrame: Within 28 days following admission to hospital following injury.
measure: Ventilator Associated Pneumonia.
timeFrame: At any point during the hospitalization.
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
Study officials:
affiliation: University of Washington
name: Grant O'Keefe, MD
role: PRINCIPAL_INVESTIGATOR
References: