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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Fund for Scientific Research, Flanders, Belgium
Baxter Healthcare Corporation
Information provided by (Responsible Party):
Greet Van den Berghe, Katholieke Universiteit Leuven
ClinicalTrials.gov Identifier:
NCT00512122
First received: July 31, 2007
Last updated: July 31, 2013
Last verified: July 2013

July 31, 2007
July 31, 2013
August 2007
February 2011   (final data collection date for primary outcome measure)
Length of stay in ICU and length of stay in the hospital. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
length of stay in ICU and the hospital [ Time Frame: 2 years ]
Complete list of historical versions of study NCT00512122 on ClinicalTrials.gov Archive Site
  • Death (hospital and ICU mortality and 90 days mortality) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Days to weaning from mechanical ventilation [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • The need for renal replacement therapies [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • The presence or absence of new kidney injury during intensive care [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Days of vasopressor or inotropic support [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • The need for tracheotomy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • The presence or absence of hyper-inflammation within five days after ICU admission [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Blood lipid profiles and albumin on days one, five, ten, and fifteen after admission [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • The presence or absence of bacteraemia, ventilator-associated pneumonia and of wound infections [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Episodes of hypoglycaemic events (defined as glycemia less than 40 mg/dl) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Amount and type of calories delivered [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Muscle strength: among others: Medical Research Council Sum Score and Maximum Inspiratory Pressure in patients staying more than 7 days in ICU. Presence of electrophysiological signs of critical illness polyneuropathy or myopathy in these patients. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Rehabilitation: among others: six minute walking distance and activities of daily life at hospital discharge.Medical Outcomes Study 36 items short form (SF 36) questionnaire two years after randomization. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Death (hospital and ICU mortality) [ Time Frame: 2 years ]
  • Days to weaning from mechanical ventilation [ Time Frame: 2 years ]
  • The need for renal replacement therapies [ Time Frame: 2 years ]
  • The presence or absence of new kidney injury during intensive care [ Time Frame: 2 years ]
  • Days of vasopressor or inotropic support [ Time Frame: 2 years ]
  • The presence or absence of hyperbilirubinemia and liversteatosis [ Time Frame: 2 years ]
  • The need for tracheotomy [ Time Frame: 2 years ]
  • The presence or absence of hyper-inflammation within five days after ICU admission [ Time Frame: 2 years ]
  • Blood lipid profiles and albumin on days one, five, ten, and 15 after admission [ Time Frame: 2 years ]
  • The presence or absence of bacteraemia, ventilator-associated pneumonia and of wound infections [ Time Frame: 2 years ]
  • Episodes of hypoglycaemic events (defined as glycemia less than 40 mg/dl) [ Time Frame: 2 years ]
  • Amount and type of calories delivered [ Time Frame: 2 years ]
  • Muscle strength and rehabilitation [ Time Frame: 3 years ]
Not Provided
Not Provided
 
Impact of Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients
Impact of Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Critical Illness
  • Starvation
  • Other: Withholding PN during the first week of ICU stay
    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.
  • Drug: Oliclinomel N71000 OR N71000E // Clinimix N17G35 OR N17G35E
    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.
    Other Name: Parenteral nutrition ATC code B05BA10
  • Experimental: EN only
    Intervention: Other: Withholding PN during the first week of ICU stay
  • Active Comparator: EN plus early PN
    Intervention: Drug: Oliclinomel N71000 OR N71000E // Clinimix N17G35 OR N17G35E

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
4640
December 2015
February 2011   (final data collection date for primary outcome measure)

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.)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Belgium
 
NCT00512122
EPaNIC 2007 1-2-2, ISRCTN 76223876, EudraCT 2007-000169-40, S 50404
Yes
Greet Van den Berghe, Katholieke Universiteit Leuven
Katholieke Universiteit Leuven
  • Fund for Scientific Research, Flanders, Belgium
  • Baxter Healthcare Corporation
Study Director: Greet Van den Berghe, MD Ph D Director of the Department of Intensive Care Medicine Catholic Univeresity Leuven
Principal Investigator: Michaël P Casaer, MD Department of Intensive Care Medicine Catholic University Leuven
Principal Investigator: Alexander P Wilmer, MD Ph D Department of Medicine Catholic University Leuven
Principal Investigator: Jasperina Dubois, MD Surgical Intensive Care Unit Regional Hospital Jessa
Katholieke Universiteit Leuven
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP