The Impact of Intervention With High-protein Enteral Formula in SICU.

Study Overview
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Brief Summary
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The advantage of higher protein intake has been pointed for critically ill patients. However, it is not easy to achieve no overfeeding but adequate protein intakes for critically ill patients. It is thus important to conduct a strategy to deliver an adequate protein under but no overfeeding for critically ill patients. The purpose of this study is to investigate the association of protein intakes with clinical outcomes by delivering high-protein pre-digested enteral formula to surgical critically ill patients. We are going to recruit 160 surgical critically ill patients. Patients would be randomly assigned to either control or experimental group. Very-high protein pre-digested formula (37% of energy) would be given to the experimental group, while standard-high protein formula (16% of energy) would be given to the control group for at least 3 days to up to 7 days. The patients' data were collected or calculated and included basic characteristics, mean energy and protein intakes, clinical outcomes (APACHE II score, comorbidities, days in hospital to ICU admission, length of ventilator dependence, hospital and ICU stays, and survival days). We anticipated that the results of this study could provide the benefit of high protein delivery on clinical outcomes for critically ill patients.

Detailed Description
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Trial Design and Patient Population This study is an investigator-initiated, prospective, randomized controlled trial. This study is conducted according to the guidelines laid down in the Declaration of Helsinki, and all procedures were reviewed as well as approved by the Regional Hospital Ethics Committee. The written informed consent will be obtained before randomization. We will collect subjects' demographic and clinical characteristics on the first and seventh day of the intervention, including age, gender, weight, height, body mass index (BMI), Disease diagnosis, disease severity (The Acute physiology and Chronic Health Evaluation II, APACHE II), Sequential Organ Failure Assessment (SOFA) Score, disease history, ventilator parameters, body temperature, blood pressure, pulse rate and breathing frequency. The complications, length of stay in intensive care unit, total hospitalization Days, hospital mortality, 14-day survival results, 28-day survival results, days of ventilator use will be also recorded. Patients 20 years of age or older will be eligible for inclusion if they have been admitted to the surgical Intensive Care Unit (SICU) for 24 hours or more. Subjects with enteral nutrition to be clinically contraindicated by treating clinician considered will be excluded. Total of one hundred and sixty patients will be included and randomly assigned into two groups. Anthropometric and Biochemical Assessments The patients' caloric requirement will be calculated based on the guidelines for critically ill nutrition treatment published by ASPEN/SCCM in 2016, suggesting that critically ill patients should be given 25 calories per kilogram of ideal body weight. The protein requirement of patients will be calculated based on the 1.5 g/kg/day recommended by the 2017 ESPEN guidelines for the nutritional care of critically ill surgical patients. The nutritional intake and digestive tract symptoms of the patient within 7 days after entering the intensive care unit will be recorded, including nutritional intake (calories, carbohydrate, protein, fat) of enteral nutrition as well as intravenous nutrition(dosage of propofol, glucose infusion and glucosaline used...etc.),and digestive symptoms (diarrhea, bloating, Abdominal pain, constipation, nausea, vomiting... etc.). The biochemical assessments of patients will be measured on the first and seventh days of admission to the ICU, including blood routine examination, total lymphocyte counts, creatinine, blood urine nitrogen, alanine aminotransferase (ALT), aspirate aminotransferase (AST), total bilirubin, albumin, prealbumin, total protein, cholesterol, triglyceride, uric acid, electrolyte, C-reactive protein, blood sugar as well as 24-hour urine urea nitrogen (UUN). Total Lymphocyte Count and Nitrogen Balance are calculated by the following formulae. Total Lymphocyte Count (cells/mm3) = WBC×% lymphocyte Nitrogen Balance (gm/day) = (protein intake/6.25) - (UUN + 4 g obligatory loss) Intervention Formula In-kind support will be provided by Nestlé Health Science, which supplied both of the enteral nutrition formulations, Peptamen® Intense VHP and Peptamen®. Peptamen® Intense VHP (37% protein of total energy) and Peptamen® (16% protein of total energy) will be provided to two groups of subjects respectively. The trial enteral nutrition was administered for at least 3 days up to 7 days or until the patient discontinued enteral nutrition, or was discharged from the ICU, whichever occurred first.

Official Title
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The Impact of Intervention With High-protein Pre-digested Enteral Formula on Clinical Outcomes in Surgical Critically Ill Patients.

Conditions
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Enteral Nutrition, Critical Illness

Intervention / Treatment
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* Other: Very-high protein enteral formula
* Other: Standard-high protein enteral formula


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 20 years of age or older. Those who have stayed in the surgical intensive care unit for 24 hours or more. Exclusion Criteria: Those who cannot supply enteral nutrition within 3 days due to disease or unstable clinical conditions. Those who have been fed for less than three days due to disease or unstable clinical conditions.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VHP(very-high protein) group<br>In VHP(very-high protein) group, we will provide pre-digested formula of 37% protein to the experimental group for at least 3 days to up to 7 days. | Other: Very-high protein enteral formula<br>* Peptamen® Intense VHP (37% protein)<br>|
| Active Comparator: SHP(standard-high protein) group<br>SHP(standard-high protein) group is the control group, standard-high protein formula (16% of energy) would be given to the control group for at least 3 days to up to 7 days. | Other: Standard-high protein enteral formula<br>* Peptamen® (16% protein)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival rate | The percentage of people in two-arm group was still alive for 28-days of time after admission to ICU. | 28 days | 
| Survival rate | The percentage of people in two-arm group was still alive for 14-days of time after admission to ICU. | 14 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU days | ICU days is the duration of a single episode of ICU. It is calculated by subtracting day of ICU admission from day of ICU discharge. | 28 days | 
| Hospital days | Hospital days, be equal length of stay (LOS), is the duration of a single episode of hospitalization. It is calculated by subtracting day of admission from day of discharge. | 28 days | 
| Length of ventilator | Length of ventilator is the total days of using ventilator. It is calculated by recording whether ventilator was used on the day in ICU. | 28 days | 
| Nitrogen balance | Nitrogen balance, calculated by measuring urine urea nitrogen (UUN) to assess whether the protein state is sufficient. | 7 days |