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Impact of Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC)

Primary Purpose

Critical Illness, Starvation

Status
Active
Phase
Phase 4
Locations
Belgium
Study Type
Interventional
Intervention
Withholding PN during the first week of ICU stay
Oliclinomel N71000 OR N71000E // Clinimix N17G35 OR N17G35E
Sponsored by
KU Leuven
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Critical Illness focused on measuring early parenteral nutrition, critical illness, respiratory failure, kidney failure, hepatic failure, muscle strength, rehabilitation, overfeeding, Reduced Oral Intake

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patients admitted to any of the five intensive care units
  2. Older than 18 years
  3. Nutritional risk screening score (NRS) higher or equal to three upon ICU admission

Exclusion Criteria:

  1. Patients with a do not resuscitate (DNR) code or moribund at the time of ICU admission
  2. Patients already enrolled in another trial
  3. Patients transferred from another intensive care unit with an established nutritional therapy
  4. Patients suffering from ketoacidotic or hyperosmolar coma on admission
  5. Patients with a body mass index (BMI) below 17 kg/m^2
  6. Short bowel syndrome
  7. Patients known to be pregnant or nursing
  8. Patients on mechanical ventilation at home
  9. NRS score lower than three
  10. Patient readmitted to ICU after randomization to the EPaNIC trial.
  11. Patient not critically ill on admission. (No clinical indication for central intravenous catheter or patient ready for oral nutrition on admission.)

Sites / Locations

  • Surgical Intensive Care Unit Regional Hospital Jessa
  • Medical Intensive Care Unit
  • Surgical Intensive Care Unit, Catholic University Leuven University Hospitals

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

EN only

EN plus early PN

Arm Description

Withholding PN during the first week of ICU stay

Oliclinomel N71000 OR N71000E // Clinimix N17G35 OR N17G35E Parenteral nutrition targeted at covering calculated needs together with the enteral nutrition intake that is achieved

Outcomes

Primary Outcome Measures

Length of stay in ICU and length of stay in the hospital.

Secondary Outcome Measures

Death (hospital and ICU mortality and 90 days mortality)
Days to weaning from mechanical ventilation
The need for renal replacement therapies
The presence or absence of new kidney injury during intensive care
Days of vasopressor or inotropic support
The presence or absence of signs of ICU liver disease: hyperbilirubinemia (defined as bilirubin level > 3 mg/dl), presence of liversteatosis, sludge…
The need for tracheotomy
The presence or absence of hyper-inflammation within five days after ICU admission
Blood lipid profiles and albumin on days one, five, ten, and fifteen after admission
The presence or absence of bacteraemia, ventilator-associated pneumonia and of wound infections
Episodes of hypoglycaemic events (defined as glycemia less than 40 mg/dl)
Amount and type of calories delivered
Muscle strength: among others: MRCss, Maximum Inspiratory Pressure in patients staying more than 7 days in ICU and a subset staying < 7 days, as well as in individuals who have never stayed in ICU. Presence of electrophysiological signs of CIP/CIM.
Rehabilitation/functionality: among others: six minute walking distance and activities of daily life at hospital discharge and at follow-up moments. SF 36 questionnaire at several follow-up moments and in individuals who have never stayed in ICU.

Full Information

First Posted
July 31, 2007
Last Updated
March 8, 2022
Sponsor
KU Leuven
Collaborators
Fund for Scientific Research, Flanders, Belgium, Baxter Healthcare Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT00512122
Brief Title
Impact of Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients
Acronym
EPaNIC
Official Title
Impact of Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 2007 (undefined)
Primary Completion Date
February 2011 (Actual)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
KU Leuven
Collaborators
Fund for Scientific Research, Flanders, Belgium, Baxter Healthcare Corporation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In critically ill patients, a strategy aimed at an early delivery of full caloric support, with a combination of Enteral Nutrition (EN) and Parenteral Nutrition (PN) (in conditions preventing hyperglycemia and overfeeding), results in shorter ICU and hospital stay and less morbidity as compared to a strategy using only EN.
Detailed Description
Written informed consent will be obtained from the patient or the closest family member or legal guardian. The family member or the patient can withdraw from the trial, at any time, without impact on his treatment or penalty. The investigators confirm that this study concerns a condition that directly threatens patient health and that the adult patient not able to give consent suffers from the condition. The experiment is essential to confirm the results from earlier research in patients who could consent or from other research methods. On admission patients will be randomly assigned to receive EN combined with early PN or only EN. At ICU admission, consecutive patients will be randomly assigned to one of these two treatment groups using blinded envelopes, stratified according to primary diagnostic category on admission. Upon addition of the new study site, the numbered en sealed envelopes for randomization stratified according to primary diagnostic category on admission were replaced by an identical digital system allowing central randomization. As initial nutritional support, patients randomised to the 'EN combined with early PN' group will receive glucose 20% at 40 ml/hr. EN will be initiated in the evening of the second ICU hospitalisation day, PN will be started the morning of the third ICU hospitalisation day. The amount of PN to be given on any particular day will be the difference between calculated caloric needs and the calories delivered by EN the previous 24 hours. When EN covers 80% of calculated caloric needs PN will be stopped. When the patient is able to eat, the parenteral regimen will be reduced and eventually stopped. Whenever oral (+ enteral) intake is below 50% of calculated caloric needs, the PN will be (re)-started. As initial nutritional support, patients randomised to the 'EN only' group will receive glucose 5% at 40 ml/hr. EN will be initiated on the evening of the second ICU day. From the morning of the third ICU hospitalisation day on, the amount of glucose 5% to be given will be the same as the volume of PN the patient theoretically would require to receive 100% of presumed caloric needs based on the amount of EN delivered the previous 24 hours. When the patient is able to eat, the parenteral regimen (glucose 5%) will be reduced to 50% and eventually stopped. Whenever oral (+ enteral) intake is below 50% of calculated caloric needs, the PN (glucose 5%) will be (re)-started. If these patients would need to stay for more than seven days on the ICU and enteral feeding of at least 80% of the calculated calories is not possible, they will be switched to EN and PN on day eight. Common strategy for attempting early enteral nutrition in both study arms: EN will be initiated on the evening of the second ICU day, unless patients are able to eat. The increase of enteral feeding volume and the adaptation of the regimen to pathological conditions will be according to protocol. Trace elements, minerals and vitamins will be administered daily intravenously (IV) to all patients from the day of admission onwards. IV substitution will be stopped in patients receiving at least 1500 ml of EN. All patients will be treated following the intensive insulin therapy schedule - targeting a blood glucose level of 80 - 110 mg/dl - from admission until discharge or oral feeding. Patients will be weaned from the ventilator according to a standard protocol. End-of-care decisions in patients for whom further intensive care is considered to be futile will be taken in consensus by a group of two senior ICU physicians and the referring specialist, all blinded to study treatment allocation. In a subgroup of patients, pathways of inflammation and metabolism and the endocrinological impact of the intervention will be studied in blood samples and in snap-frozen in vivo biopsies of muscle and adipose tissue. Blood and tissue samples from healthy volunteers will serve as references for these exploratory studies. In some patients, radiological evolution of regional muscle and adipose tissue volumes will be evaluated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Critical Illness, Starvation
Keywords
early parenteral nutrition, critical illness, respiratory failure, kidney failure, hepatic failure, muscle strength, rehabilitation, overfeeding, Reduced Oral Intake

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Investigator
Masking Description
All outcome adjudicators were unaware of study-group assignments
Allocation
Randomized
Enrollment
4640 (Actual)

8. Arms, Groups, and Interventions

Arm Title
EN only
Arm Type
Experimental
Arm Description
Withholding PN during the first week of ICU stay
Arm Title
EN plus early PN
Arm Type
Active Comparator
Arm Description
Oliclinomel N71000 OR N71000E // Clinimix N17G35 OR N17G35E Parenteral nutrition targeted at covering calculated needs together with the enteral nutrition intake that is achieved
Intervention Type
Other
Intervention Name(s)
Withholding PN during the first week of ICU stay
Intervention Description
Patients in this arm will receive exclusively enteral nutrition. If enteral nutrition is insufficient after the seventh day of ICU stay, parenteral nutrition will be started.
Intervention Type
Drug
Intervention Name(s)
Oliclinomel N71000 OR N71000E // Clinimix N17G35 OR N17G35E
Other Intervention Name(s)
Parenteral nutrition ATC code B05BA10
Intervention Description
PN will be started the morning of the third ICU hospitalisation day. The amount of PN to be given will be calculated to cover the caloric needs of the patient, based on the enteral energy intake the previous 24 hours.
Primary Outcome Measure Information:
Title
Length of stay in ICU and length of stay in the hospital.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Death (hospital and ICU mortality and 90 days mortality)
Time Frame
10 years
Title
Days to weaning from mechanical ventilation
Time Frame
2 years
Title
The need for renal replacement therapies
Time Frame
2 years
Title
The presence or absence of new kidney injury during intensive care
Time Frame
2 years
Title
Days of vasopressor or inotropic support
Time Frame
2 years
Title
The presence or absence of signs of ICU liver disease: hyperbilirubinemia (defined as bilirubin level > 3 mg/dl), presence of liversteatosis, sludge…
Time Frame
2 years
Title
The need for tracheotomy
Time Frame
2 years
Title
The presence or absence of hyper-inflammation within five days after ICU admission
Time Frame
2 years
Title
Blood lipid profiles and albumin on days one, five, ten, and fifteen after admission
Time Frame
2 years
Title
The presence or absence of bacteraemia, ventilator-associated pneumonia and of wound infections
Time Frame
2 years
Title
Episodes of hypoglycaemic events (defined as glycemia less than 40 mg/dl)
Time Frame
2 years
Title
Amount and type of calories delivered
Time Frame
2 years
Title
Muscle strength: among others: MRCss, Maximum Inspiratory Pressure in patients staying more than 7 days in ICU and a subset staying < 7 days, as well as in individuals who have never stayed in ICU. Presence of electrophysiological signs of CIP/CIM.
Time Frame
10 years
Title
Rehabilitation/functionality: among others: six minute walking distance and activities of daily life at hospital discharge and at follow-up moments. SF 36 questionnaire at several follow-up moments and in individuals who have never stayed in ICU.
Time Frame
10 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients admitted to any of the five intensive care units Older than 18 years Nutritional risk screening score (NRS) higher or equal to three upon ICU admission Exclusion Criteria: Patients with a do not resuscitate (DNR) code or moribund at the time of ICU admission Patients already enrolled in another trial Patients transferred from another intensive care unit with an established nutritional therapy Patients suffering from ketoacidotic or hyperosmolar coma on admission Patients with a body mass index (BMI) below 17 kg/m^2 Short bowel syndrome Patients known to be pregnant or nursing Patients on mechanical ventilation at home NRS score lower than three Patient readmitted to ICU after randomization to the EPaNIC trial. Patient not critically ill on admission. (No clinical indication for central intravenous catheter or patient ready for oral nutrition on admission.)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Greet Van den Berghe, MD Ph D
Organizational Affiliation
Director of the Department of Intensive Care Medicine Catholic Univeresity Leuven
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Michaël P Casaer, MD
Organizational Affiliation
Department of Intensive Care Medicine Catholic University Leuven
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alexander P Wilmer, MD Ph D
Organizational Affiliation
Department of Medicine Catholic University Leuven
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jasperina Dubois, MD
Organizational Affiliation
Surgical Intensive Care Unit Regional Hospital Jessa
Official's Role
Principal Investigator
Facility Information:
Facility Name
Surgical Intensive Care Unit Regional Hospital Jessa
City
Hasselt
ZIP/Postal Code
3500
Country
Belgium
Facility Name
Medical Intensive Care Unit
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Surgical Intensive Care Unit, Catholic University Leuven University Hospitals
City
Leuven
ZIP/Postal Code
3000
Country
Belgium

12. IPD Sharing Statement

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Links:
URL
https://gbiomed.kuleuven.be/english/research/50000618/50000663/
Description
Katholieke Universiteit Leuven Homepage
URL
http://www.trialsjournal.com/content/12/1/21/abstract
Description
Casaer et al.: Impact of early parenteral nutrition completing enteral nutrition in adult critically ill patients (EPaNIC trial): a study protocol and statistical analysis plan for a randomized controlled trial. Trials 2011 12:21.

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Impact of Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients

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