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Supplemental Enteral Protein in Critical Illness

Protein-enhanced Enteral Nutrition and Metabolomics in Critically Ill Trauma and Surgical Patients

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03170401
Enrollment
500
Registered
2017-05-31
Start date
2016-11-30
Completion date
2022-12-31
Last updated
2024-06-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Critical Illness, Nutrition Disorder, Trauma

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.

Interventions

DIETARY_SUPPLEMENTProtein supplementation

enteral protein supplementation

Standard enteral nutrition.

Sponsors

National Institute of General Medical Sciences (NIGMS)
CollaboratorNIH
University of Washington
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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.

Design outcomes

Primary

MeasureTime frameDescription
Serum Concentrations of Transthyretin at 3 Weeks After Injury.3 weeks after admission for injuryTransthyretin is a circulating biomarker of nutritional status and protein synthesis.

Secondary

MeasureTime frameDescription
Ventilator-free Days.Within 28 days following admission to hospital following injury.Ventilator-free days will measured in the standard way and indicate the number of days a subject was alive and not receiving mechanical ventilation during the first 28 days.
Ventilator Associated Pneumonia.At any point during the hospitalization.Pneumonia diagnosed while the patient is receiving mechanical ventilation as recorded in the institutional administrative trauma registry and ICU quality assurance database.

Countries

United States

Participant flow

Recruitment details

Potential study subjects included those admitted to the trauma and surgical intensive care services at Harborview Medical Center. Patients were screened by a member of the study team and were considered for inclusion if they were receiving mechanical ventilation expected to require ICU care for \>7 days, deemed ready to start enteral nutritional support by the attending physician within 24 - 72 hours of admission, and had no contraindications to full enteral support.

Pre-assignment details

No enrolled subjects were excluded prior to assignment to groups.

Participants by arm

ArmCount
no Protein Supplementation
trauma and critically ill surgical patients receiving enteral nutrition without any protein supplementation
256
Protein Supplementation
trauma and critically ill surgical patients receiving enteral nutrition with additional protein supplementation
244
Total500

Baseline characteristics

Characteristicno Protein SupplementationTotalProtein Supplementation
Age, Continuous49 years47 years45 years
Ethnicity (NIH/OMB)
Hispanic or Latino
26 Participants53 Participants27 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
224 Participants434 Participants210 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
6 Participants13 Participants7 Participants
Race (NIH/OMB)
American Indian or Alaska Native
10 Participants15 Participants5 Participants
Race (NIH/OMB)
Asian
11 Participants20 Participants9 Participants
Race (NIH/OMB)
Black or African American
17 Participants37 Participants20 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
2 Participants2 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
6 Participants12 Participants6 Participants
Race (NIH/OMB)
White
210 Participants414 Participants204 Participants
Region of Enrollment
United States
256 participants500 participants244 participants
Sex: Female, Male
Female
54 Participants114 Participants60 Participants
Sex: Female, Male
Male
202 Participants386 Participants184 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
34 / 25636 / 244
other
Total, other adverse events
136 / 256164 / 244
serious
Total, serious adverse events
31 / 25662 / 244

Outcome results

Primary

Serum Concentrations of Transthyretin at 3 Weeks After Injury.

Transthyretin is a circulating biomarker of nutritional status and protein synthesis.

Time frame: 3 weeks after admission for injury

ArmMeasureValue (MEAN)Dispersion
no Protein SupplementationSerum Concentrations of Transthyretin at 3 Weeks After Injury.18.1 mg/dlStandard Deviation 8
Protein SupplementationSerum Concentrations of Transthyretin at 3 Weeks After Injury.18.9 mg/dlStandard Deviation 8.5
Secondary

Ventilator Associated Pneumonia.

Pneumonia diagnosed while the patient is receiving mechanical ventilation as recorded in the institutional administrative trauma registry and ICU quality assurance database.

Time frame: At any point during the hospitalization.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
no Protein SupplementationVentilator Associated Pneumonia.58 Participants
Protein SupplementationVentilator Associated Pneumonia.45 Participants
Secondary

Ventilator-free Days.

Ventilator-free days will measured in the standard way and indicate the number of days a subject was alive and not receiving mechanical ventilation during the first 28 days.

Time frame: Within 28 days following admission to hospital following injury.

ArmMeasureValue (MEAN)Dispersion
no Protein SupplementationVentilator-free Days.15.0 daysStandard Deviation 9.7
Protein SupplementationVentilator-free Days.13.9 daysStandard Deviation 9.8

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026