The Energy Dose Study

Phase 2

Terminated

Conditions: Critical Illness

Interventions: Drug: Parenteral Nutrition
Drug: Propofol
Drug: Clevidipine
Drug: Dextrose-containing IV Fluids
Drug: Enteral feeding

Registration Number: NCT01369147

Lead Sponsor: Emory University

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 12

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Parenteral nutrition energy dose at 0.6 x measured REE	Parenteral Nutrition	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.
Parenteral nutrition energy dose at 0.6 x measured REE	Propofol	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.
Parenteral nutrition energy dose at 0.6 x measured REE	Clevidipine	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.
Parenteral nutrition energy dose at 0.6 x measured REE	Dextrose-containing IV Fluids	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.
Parenteral nutrition energy dose at 0.6 x measured REE	Enteral feeding	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.
Parenteral nutrition energy dose at 1.0 x measured REE	Parenteral Nutrition	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.
Parenteral nutrition energy dose at 1.0 x measured REE	Propofol	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.
Parenteral nutrition energy dose at 1.0 x measured REE	Dextrose-containing IV Fluids	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.
Parenteral nutrition energy dose at 1.3 x measured REE	Dextrose-containing IV Fluids	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.
Parenteral nutrition energy dose at 1.0 x measured REE	Enteral feeding	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.
Parenteral nutrition energy dose at 1.3 x measured REE	Parenteral Nutrition	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.
Parenteral nutrition energy dose at 1.3 x measured REE	Enteral feeding	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.
Parenteral nutrition energy dose at 1.0 x measured REE	Clevidipine	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.
Parenteral nutrition energy dose at 1.3 x measured REE	Propofol	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.
Parenteral nutrition energy dose at 1.3 x measured REE	Clevidipine	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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