The Energy Dose Study

Study Overview
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Brief Summary
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The investigators have designed this single-center Randomized Clinical Trial (RCT) to prospectively compare, for the first time, the clinical efficacy of different energy doses in intensive care unit (ICU) patients requiring parenteral nutrition (PN) due to intestinal failure/dysfunction. This study intends to enroll a total of 60 patients (20 per energy dose group) to generate critical preliminary data needed to inform subsequent appropriately powered Phase III multicenter trials.

Detailed Description
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Protein and/or energy deficits are associated with increased rates of hospital infection, skeletal muscle weakness, impaired wound healing, and prolonged convalescence in ICU patients. To prevent or treat malnutrition, enteral nutrition (EN) and/or parenteral nutrition (PN) are routinely given worldwide to a significant proportion of ICU patients. Optimal caloric requirements in critically ill patients are unknown due to a lack of rigorous randomized clinical trials. The comparative efficacy of energy doses in critically ill patients is unknown and clinical recommendations are conflicting and controversial. The primary aim of this study is to perform a controlled, double-blind, prospective, randomized, intent-to-treat Phase II clinical trial to test the efficacy of three specific energy doses on 28-day total hospital-acquired infections (primary endpoint), blood stream infections (BSI), and other important clinical outcomes in medical/surgical ICU patients requiring specialized parenteral ± enteral feeding. The investigators would also determine the impact of cumulative and mean daily 28-day energy deficits on clinical outcome endpoints; the practical utility of estimated resting energy expenditure (REE) determined by Harris-Benedict equation versus measured REE across different energy doses. The investigators would also like to determine the impact of administered energy dose and energy deficits on global metabolomic patterns over time and their association with key clinical outcomes. Participants will be randomized to receive one of three specific energy doses, 0.6, 1.0 and 1.3 times measured REE, given for 28 consecutive days during the ICU and post-ICU course.

Official Title
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Comparative Effectiveness of Energy Doses in Critical Illness

Conditions
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Critical Illness

Intervention / Treatment
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* Drug: Parenteral Nutrition
* Drug: Propofol
* Drug: Clevidipine
* Drug: Dextrose-containing IV Fluids
* Drug: Enteral feeding


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A signed informed consent is in place on the patient's chart The patient is at least 18 but not more than 90 years of age at time of ICU admission The patient has a body mass index (BMI) less than 40 kg/m^2 The patient has been admitted to either a medical or surgical (non-neurological) ICU and is expected to survive and remain in the ICU for at least 72 hours after entry There is central venous access for administration of the study PN The patient's primary physician(s) will allow the investigative team to manage the study PN and enteral feedings during the current hospitalization The patient is expected to require total or partial central venous PN for 7 or more subsequent days after entry on a clinical basis Exclusion Criteria: The patient is pregnant The patient has unresuscitated clinical sepsis, defined as unstable blood pressure despite vasopressor support and mean arterial pressure (MAP) < 60 mm Hg on at least 3 consecutive readings within a 3-hour period during the 24 hours prior to study entry The patient was admitted to the ICU following trauma or burns The patient has significant renal dysfunction (defined as serum creatinine > 2.5 mg/dL or deemed to have significant acute kidney injury by the primary physicians) and is not receiving continuous renal replacement therapy (CRRT) or intermittent hemodialysis The patient has previously undergone an organ transplantation The patient has a current malignancy or is currently receiving an active regimen of chemotherapy and/or radiotherapy to treat a previously diagnosed malignancy The patient has a history of HIV/AIDS The patient has received any investigational drug within 60 days prior to study entry The patient is unable or unwilling to participate in study procedures such as longitudinal blood draws and administration of study nutrient formulations

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Parenteral nutrition energy dose at 0.6 x measured REE<br>Participants in this study arm will be provided a total daily calorie (kcal) intake at 0.6 x REE for up to 28 days. The dose of parenteral nutrition (PN) will be adjusted taking into account any calories from propofol, clevidipine, dextrose-containing IV fluids surpassing 500 mL/day, and any enteral feedings, to obtain the energy dose that the participant was randomized to receive. | Drug: Parenteral Nutrition<br>* The PN dose will be written for each 24-hr period taking into account any kilocalories (kcal) provided as part of standard of care from propofol, clevidipine, dextrose-containing IV fluid exceeding 500 mL/day, and enteral feedings.<br>Drug: Propofol<br>* The PN dose will be written for each 24-hr period taking into account calories provided as lipid emulsion in the sedative propofol (1.1 kcal/mL).<br>* Other names: Diprivan;Drug: Clevidipine<br>* The PN dose will be written for each 24-hr period taking into account calories provided as lipid emulsion in clevidipine (2 kcal/mL).<br>* Other names: Cleviprex;Drug: Dextrose-containing IV Fluids<br>* The PN dose will be written for each 24-hr period taking into account calories provided from dextrose-containing IV fluid orders exceeding 500 mL/day.<br>Drug: Enteral feeding<br>* Enteral nutrition is caloric intake through the gastrointestinal (GI) tract via food consumed through the mouth or a feeding tube delivering nutrition directly to the stomach or small intestines. The PN dose will be written for each 24-hr period taking into account calories provided from any enteral feedings.<br>|
| Active Comparator: Parenteral nutrition energy dose at 1.0 x measured REE<br>Participants in this study arm will be provided a total daily calorie (kcal) intake at 1.0 x REE for up to 28 days. The dose of PN will be adjusted taking into account any calories from propofol, clevidipine, dextrose-containing IV fluids surpassing 500 mL/day, and any enteral feedings, to obtain the energy dose that the participant was randomized to receive. | Drug: Parenteral Nutrition<br>* The PN dose will be written for each 24-hr period taking into account any kilocalories (kcal) provided as part of standard of care from propofol, clevidipine, dextrose-containing IV fluid exceeding 500 mL/day, and enteral feedings.<br>Drug: Propofol<br>* The PN dose will be written for each 24-hr period taking into account calories provided as lipid emulsion in the sedative propofol (1.1 kcal/mL).<br>* Other names: Diprivan;Drug: Clevidipine<br>* The PN dose will be written for each 24-hr period taking into account calories provided as lipid emulsion in clevidipine (2 kcal/mL).<br>* Other names: Cleviprex;Drug: Dextrose-containing IV Fluids<br>* The PN dose will be written for each 24-hr period taking into account calories provided from dextrose-containing IV fluid orders exceeding 500 mL/day.<br>Drug: Enteral feeding<br>* Enteral nutrition is caloric intake through the gastrointestinal (GI) tract via food consumed through the mouth or a feeding tube delivering nutrition directly to the stomach or small intestines. The PN dose will be written for each 24-hr period taking into account calories provided from any enteral feedings.<br>|
| Experimental: Parenteral nutrition energy dose at 1.3 x measured REE<br>Participants in this study arm will be provided a total daily calorie (kcal) intake at 1.3 x REE for up to 28 days. The dose of PN will be adjusted taking into account any calories from propofol, clevidipine, dextrose-containing IV fluids surpassing 500 mL/day, and any enteral feedings, to obtain the energy dose that the participant was randomized to receive. | Drug: Parenteral Nutrition<br>* The PN dose will be written for each 24-hr period taking into account any kilocalories (kcal) provided as part of standard of care from propofol, clevidipine, dextrose-containing IV fluid exceeding 500 mL/day, and enteral feedings.<br>Drug: Propofol<br>* The PN dose will be written for each 24-hr period taking into account calories provided as lipid emulsion in the sedative propofol (1.1 kcal/mL).<br>* Other names: Diprivan;Drug: Clevidipine<br>* The PN dose will be written for each 24-hr period taking into account calories provided as lipid emulsion in clevidipine (2 kcal/mL).<br>* Other names: Cleviprex;Drug: Dextrose-containing IV Fluids<br>* The PN dose will be written for each 24-hr period taking into account calories provided from dextrose-containing IV fluid orders exceeding 500 mL/day.<br>Drug: Enteral feeding<br>* Enteral nutrition is caloric intake through the gastrointestinal (GI) tract via food consumed through the mouth or a feeding tube delivering nutrition directly to the stomach or small intestines. The PN dose will be written for each 24-hr period taking into account calories provided from any enteral feedings.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Hospital-acquired Infection | The number of participants with a hospital-acquired infection during the study period is presented here. | Up to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Bloodstream Infection | The count of participants acquiring a bloodstream infection during the study period is presented here. | Up to Day 28 | 
| Ventilator Free Days | The mean number of ICU ventilator-free days among participants. | Up to Day 28 | 
| Number of Days in Intensive Care Unit (ICU) | The ICU length of stay (in days) is presented here for each study arm. | Up to 28 Days | 
| Number of Days in Hospital | The hospitalization length of stay (in days) is presented here for each study arm. | Up to Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Surgical Intensive Care Unit (SICU), Calories, Total Parenteral Nutrition (TPN), Tube Feeding, Optimum Energy Dose in SICU, Malnutrition, Hospital-acquired Infection