The Energy Dose Study

Comparative Effectiveness of Energy Doses in Critical Illness

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01369147

Enrollment

Registered

2011-06-08

Start date

2011-07-31

Completion date

2014-12-02

Last updated

2022-06-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Critical Illness

Keywords

Surgical Intensive Care Unit (SICU), Calories, Total Parenteral Nutrition (TPN), Tube Feeding, Optimum Energy Dose in SICU, Malnutrition, Hospital-acquired Infection

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.

Interventions

DRUGParenteral Nutrition

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.

DRUGPropofol

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).

DRUGClevidipine

The PN dose will be written for each 24-hr period taking into account calories provided as lipid emulsion in clevidipine (2 kcal/mL).

DRUGDextrose-containing IV Fluids

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.

DRUGEnteral feeding

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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SUPPORTIVE_CARE

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 90 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.

Other

Measure	Time frame	Description
Cumulative 28-day Energy Deficit	Up to Day 28	The daily energy deficit of kilocalories was calculated by subtracting the calculated mean daily Measured Resting Energy Expenditure (measured using a metabolic cart) from the actual daily energy intake obtained from participant nutrition intake records. The cumulative energy deficit is the sum of daily energy deficits during the time participants were hospitalized, up to 28 days.
Mean Daily Energy Deficit	Up to Day 28	The daily energy deficit of kilocalories was calculated by subtracting the calculated mean daily Measured Resting Energy Expenditure (measured using a metabolic cart) from the actual daily energy intake obtained from participant nutrition intake records. The mean daily energy deficit was calculated during the time participants were hospitalized, up to 28 days.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Parenteral Nutrition Energy Dose at 0.6 x Measured REE Participants in this study arm were provided a total daily calorie (kcal) intake at 0.6 x REE for up to 28 days. The dose of parenteral nutrition (PN) was 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.	3
Parenteral Nutrition Energy Dose at 1.0 x Measured REE Participants in this study arm were provided a total daily calorie (kcal) intake at 1.0 x REE for up to 28 days. The dose of parenteral nutrition (PN) was 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.	4
Parenteral Nutrition Energy Dose at 1.3 x Measured REE Participants in this study arm were provided a total daily calorie (kcal) intake at 1.3 x REE for up to 28 days. The dose of parenteral nutrition (PN) was 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.	4
Total	11

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	All collected data were unintentionally destroyed	0	1	0

Baseline characteristics

Characteristic	Parenteral Nutrition Energy Dose at 0.6 x Measured REE	Total	Parenteral Nutrition Energy Dose at 1.3 x Measured REE	Parenteral Nutrition Energy Dose at 1.0 x Measured REE
Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) Score APACHE II Score Greater Than 15	2 Participants	6 Participants	2 Participants	2 Participants
Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) Score APACHE II Score of 15 or Less	1 Participants	5 Participants	2 Participants	2 Participants
Age, Continuous	47.05 years STANDARD_DEVIATION 21.5	53.66 years STANDARD_DEVIATION 15.18	51.73 years STANDARD_DEVIATION 11.2	60.56 years STANDARD_DEVIATION 14.9
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants	11 Participants	4 Participants	4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	1 Participants	3 Participants	2 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	2 Participants	8 Participants	2 Participants	4 Participants
Region of Enrollment United States	3 Participants	11 Participants	4 Participants	4 Participants
Sex: Female, Male Female	1 Participants	6 Participants	3 Participants	2 Participants
Sex: Female, Male Male	2 Participants	5 Participants	1 Participants	2 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 3	0 / 4	0 / 4
other Total, other adverse events	0 / 3	0 / 4	0 / 4
serious Total, serious adverse events	0 / 3	0 / 4	0 / 4

Outcome results

Primary

Number of Participants With Hospital-acquired Infection

The number of participants with a hospital-acquired infection during the study period is presented here.

Time frame: Up to Day 28