The Energy Dose Study

• ClinicalTrials.gov Identifier: NCT01369147
• Recruitment Status: Suspended
• First Posted: June 8, 2011
• Last Update Posted: October 30, 2019
• Sponsor: Emory University
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Thomas R. Ziegler, MD, Emory University

Study Description

Brief Summary:

The investigators have designed this pilot, single-center Randomized Clinical Trial (RCT) to prospectively compare, for the first time, the clinical efficacy of different energy doses in ICU patients requiring PN due to intestinal failure/dysfunction. A total of 60 patients will be studied (20 per energy dose group) to generate critical preliminary data needed to inform subsequent appropriately powered Phase III multicenter trials.

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 [0.6, 1.0 and 1.3 x measured REE (resting energy expenditure), respectively], given for 28 consecutive days during the ICU and post-ICU course, 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, in these subjects A) the impact of cumulative and mean daily 28-day energy deficits [energy intake-measured REE] on clinical outcome endpoints; and B) the practical utility of estimated 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.

Condition or disease	Intervention/treatment	Phase
Critical Illness	Drug: Parenteral nutrition energy dose at 0.6 x measured REE; Drug: Parenteral nutrition energy dose at 1.0 x measured REE; Drug: Parenteral nutrition energy dose at 1.3 X measured REE	Phase 2

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; this issue is the focus of this study.

The investigators have designed this pilot, single-center Randomized Clinical Trial (RCT) to prospectively compare, for the first time, the clinical efficacy of different energy doses in ICU patients requiring PN due to intestinal failure/dysfunction. A total of 60 patients will be studied (20 per energy dose group) to generate critical preliminary data needed to inform subsequent appropriately powered Phase III multicenter trials.

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 [0.6, 1.0 and 1.3 x measured REE (resting energy expenditure), respectively], given for 28 consecutive days during the ICU and post-ICU course, 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, in these subjects A) the impact of cumulative and mean daily 28-day energy deficits [energy intake-measured REE] on clinical outcome endpoints; and B) the practical utility of estimated 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.

This study will allow the researchers to generate needed data on the effect of energy dose and energy deficits on global metabolomic patterns over time that may be associated with key clinical outcomes in ICU patients. This exploratory research is also needed to develop new methods that evaluate the metabolic responses to nutrition support and their potential relationships to clinical outcomes.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Comparative Effectiveness of Energy Doses in Critical Illness
• Study Start Date: July 2011
• Estimated Primary Completion Date: October 2020
• Estimated Study Completion Date: October 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Parenteral nutrition energy dose at 0.6x measured REE; Participants in this study arm will be provided a total daily calorie (kcal) intake [from parenteral nutrition (PN) + dextrose-containing IV fluids (> 500 mL/day) + propofol/clevidipine + any enteral feedings) at 0.6 x resting energy expenditure (REE).	Drug: Parenteral nutrition energy dose at 0.6 x measured REE; Participants will be provided a total daily calorie (kcal) intake from parenteral nutrition (PN), dextrose-containing IV fluids (> 500 mL/day), propofol/clevidipine, and any enteral feedings at 0.6 x baseline metabolic energy expenditure (MEE). Total energy dosing based on real-time REE measurements will be adjusted during the ICU stay. 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) or clevidipine (2 kcal/mL), and any dextrose-containing IV fluid orders exceeding 500 mL/day. Participants will receive a maximum of 28 days of the double blind study energy dose and will be transitioned from PN to enteral feeds as soon as tolerated and clinically indicated.; Other Name: Intralipid® 30%
Active Comparator: Parenteral nutrition energy dose at 1.0 x measured REE; Participants in this study arm will be provided a total daily calorie (kcal) intake [from parenteral nutrition (PN) + dextrose-containing IV fluids (> 500 mL/day) + propofol/clevidipine + any enteral feedings) at 1.0 x resting energy expenditure (REE).	Drug: Parenteral nutrition energy dose at 1.0 x measured REE; Participants will be provided a total daily calorie (kcal) intake from parenteral nutrition (PN), dextrose-containing IV fluids (> 500 mL/day), propofol/clevidipine, and any enteral feedings at 1.0 x baseline metabolic energy expenditure (MEE). Total energy dosing based on real-time REE measurements will be adjusted during the ICU stay. 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) or clevidipine (2 kcal/mL), and any dextrose-containing IV fluid orders exceeding 500 mL/day. Participants will receive a maximum of 28 days of the double blind study energy dose and will be transitioned from PN to enteral feeds as soon as tolerated and clinically indicated.; Other Name: Intralipid® 30%
Experimental: Parenteral nutrition energy dose at 1.3 x measured REE; Participants in this study arm will be provided a total daily calorie (kcal) intake [from parenteral nutrition (PN) + dextrose-containing IV fluids (> 500 mL/day) + propofol/clevidipine + any enteral feedings) at 1.3 x resting energy expenditure (REE).	Drug: Parenteral nutrition energy dose at 1.3 X measured REE; Participants will be provided a total daily calorie (kcal) intake from parenteral nutrition (PN), dextrose-containing IV fluids (> 500 mL/day), propofol/clevidipine, and any enteral feedings at 1.3 x baseline metabolic energy expenditure (MEE). Total energy dosing based on real-time REE measurements will be adjusted during the ICU stay. 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) or clevidipine (2 kcal/mL), and any dextrose-containing IV fluid orders exceeding 500 mL/day. Participants will receive a maximum of 28 days of the double blind study energy dose and will be transitioned from PN to enteral feeds as soon as tolerated and clinically indicated.; Other Name: Intralipid® 30%

Outcome Measures

Primary Outcome Measures :

1. To compare the effect of three specific energy doses [0.6, 1.0 and 1.3 x measured Resting Energy Expenditure, respectively], on total hospital acquired infection incidence rates in patients in the ICU over a 28 day period. [ Time Frame: 2 years ]
   To perform a controlled, double-blind, prospective, randomized, parallel group, intent-to-treat Phase II clinical trial to compare the effect of three specific energy doses [0.6, 1.0 and 1.3 x measured REE (metabolic cart), respectively]on total hospital-acquired infections incidence rates in medical/surgical ICU patients, over a 28 day period.

Secondary Outcome Measures :

1. To examine the impact of cumulative and mean daily 28-day energy deficits on nosocomial infection incidence rates [ Time Frame: 2 years ]
   Daily energy deficit will be calculated by subtracting the calculated mean daily Measured Resting Energy Expenditure (using a metabolic cart) during each study week from the actual daily energy intake ( per subject nutrition intake records). We will compare the daily 28 day energy deficits for each of the three study groups to determine how they relate to the nosocomial infection incidence rates

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. A signed informed consent is in place on the patient's chart;
2. The patient is at least 18 but not more than 90 years of age at time of ICU admission;
3. The patient has a body mass index (BMI) between 18.5 and 40 kg/m2;
4. The patient has been admitted to either a medical or surgical (non-neurological) ICU within the previous 72 hours and is expected to survive and remain in the ICU for at least 96 hours after entry;
5. The patient is expected to require mechanical ventilation for at least 72 hours after entry and a metabolic cart-derived REE is possible;
6. There is central venous access for administration of the study PN;
7. The patient's primary physician(s) will allow the investigative team to manage the study PN and enteral feedings during the current hospitalization; and
8. The patient is expected to require total or partial central venous PN for 7 or more subsequent days after entry on a clinical basis (e.g. following massive small bowel ± colonic resection, the presence of high output fistulae or perforated small bowel, with demonstrated intolerance to EN or when EN may be contraindicated, as with severe diarrhea or emesis, partial or complete bowel obstruction, severe gastrointestinal bleeding and severe hemodynamic instability, such as with escalating vasopressor requirements).

Exclusion Criteria:

1. The patient is pregnant;
2. 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;
3. The patient had a do-not-resuscitate order at the time of screening;
4. The patient was admitted to the ICU following trauma or burns;
5. 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;
6. The patient has previously undergone an organ transplantation;
7. the patient has a history of cancer (except non-melanoma skin cancer that is considered cured or distant cancer diagnosed more than 5 years previously and not requiring further therapy);
8. the patient has a history of HIV/AIDS;
9. The patient has received any investigational drug within 60 days prior to study entry; and
10. The patient is unable or unwilling to participate in study procedures such as longitudinal blood draws and administration of study nutrient formulations.

Contacts and Locations

Locations

United States, Georgia

Emory University Hospital

Atlanta, Georgia, United States, 30322

Sponsors and Collaborators

Emory University

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Thomas R Ziegler, MD; Emory University

More Information

• Responsible Party: Thomas R. Ziegler, MD, Professor of Medicine, Emory University
• ClinicalTrials.gov Identifier: NCT01369147 History of Changes
• Other Study ID Numbers: IRB00049495; 1R21DK089369 ( U.S. NIH Grant/Contract )
• First Posted: June 8, 2011
• Last Update Posted: October 30, 2019
• Last Verified: October 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Thomas R. Ziegler, MD, Emory University:

SICU; calories; TPN; tube feeding; Optimum Energy Dose in SICU

Additional relevant MeSH terms:

Critical Illness; Disease Attributes; Pathologic Processes; Clevidipine; Propofol; Soybean oil, phospholipid emulsion; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Fat Emulsions, Intravenous; Parenteral Nutrition Solutions; Pharmaceutical Solutions; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents