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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01GM127790-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of General Medical Sciences (NIGMS) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| no protein supplementation | Active Comparator | subjects receiving enteral nutrition without any protein supplementation |
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| protein supplementation | Experimental | subjects receiving enteral nutrition with additional protein supplementation |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Protein supplementation | Dietary Supplement | enteral protein supplementation |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Serum Concentrations of Transthyretin at 3 Weeks After Injury. | Transthyretin is a circulating biomarker of nutritional status and protein synthesis. | 3 weeks after admission for injury |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Within 28 days following admission to hospital following injury. |
| Ventilator Associated Pneumonia. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Grant O'Keefe, MD | University of Washington | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Harborview Medical Center | Seattle | Washington | 98104 | United States |
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No enrolled subjects were excluded prior to assignment to groups.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | no Protein Supplementation | trauma subjects receiving enteral nutrition without any protein supplementation |
| FG001 | Protein Supplementation | trauma subjects receiving enteral nutrition with additional protein supplementation Protein supplementation: half the subjects will receive protein supplementation via enteral feedings and half will not receive the protein supplementation |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Study Subject Enrollment |
| |||||||||||||
| Follow up and Data Analysis |
|
For the primary outcome of serum transthyretin concentrations 129/256 participants in the no protein supplementation arm, and 122/244 participants in the protein supplementation arm had data available for analysis.
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| ID | Title | Description |
|---|---|---|
| BG000 | no Protein Supplementation | trauma and critically ill surgical patients receiving enteral nutrition without any protein supplementation |
| BG001 | Protein Supplementation | trauma and critically ill surgical patients receiving enteral nutrition with additional protein supplementation |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Serum Concentrations of Transthyretin at 3 Weeks After Injury. | Transthyretin is a circulating biomarker of nutritional status and protein synthesis. | Posted | Mean | Standard Deviation | mg/dl | 3 weeks after admission for injury |
|
Duration of hospitalization to a maximum of 1 year.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | no Protein Supplementation | trauma and critically ill surgical patients receiving enteral nutrition without any protein supplementation |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Adjudicated aspiration | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | When dual and blinded review of all episodes of hypoxemia or interruption of enteral nutrition were determined to be due to tracheal aspiration of gastric contents. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Grant E O'Keefe | University of Washingtion | 206-744-8016 | gokeefe@uw.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 15, 2023 | May 7, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 20, 2023 | May 7, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D009748 | Nutrition Disorders |
| D014947 | Wounds and Injuries |
| D016638 | Critical Illness |
| ID | Term |
|---|---|
| D009750 | Nutritional and Metabolic Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| Standard enteral nutrition |
| Other |
Standard enteral nutrition. |
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Pneumonia diagnosed while the patient is receiving mechanical ventilation as recorded in the institutional administrative trauma registry and ICU quality assurance database. |
| At any point during the hospitalization. |
| NOT COMPLETED |
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| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Units | Counts |
|---|---|
| Participants |
|
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| 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. | Posted | Mean | Standard Deviation | days | Within 28 days following admission to hospital following injury. |
|
|
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| 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. | Posted | Count of Participants | Participants | At any point during the hospitalization. |
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|
|
| 34 |
| 256 |
| 31 |
| 256 |
| 136 |
| 256 |
| EG001 | Protein Supplementation | trauma and critically ill surgical patients receiving enteral nutrition with additional protein supplementation | 36 | 244 | 62 | 244 | 164 | 244 |
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| Reintubation | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Subject required endotracheal intubation following a planned extubation. |
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| Gastrointestinal perforation | Gastrointestinal disorders | Systematic Assessment |
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| Abdominal distention | Gastrointestinal disorders | Systematic Assessment |
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| Emesis | Gastrointestinal disorders | Systematic Assessment |
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