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Critical IllnessPhase 4EPaNICNCT00512122

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

A Phase 4 study testing Withholding PN during the first week of ICU stay and Oliclinomel N71000 OR N71000E // Clinimix N17G35 OR N17G35E in people with Critical Illness and Starvation, run by KU Leuven at 3 sites in Belgium.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Critical Illness, Starvation
What is being tested?
Withholding PN during the first week of ICU stay and Oliclinomel N71000 OR N71000E // Clinimix N17G35 OR N17G35E
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4,640 participants
Where
3 sitesBelgium
Study dates
Aug 2007to Dec 2026
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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.)

Trial locations and contacts

3 sites in 1 country.

Belgium3 sites

  • Surgical Intensive Care Unit Regional Hospital Jessa

    Hasselt, 3500

  • Medical Intensive Care Unit

    Leuven, 3000

  • Surgical Intensive Care Unit, Catholic University Leuven University Hospitals

    Leuven, 3000

Other trials in Belgium

About this study

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.

Read the 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.

Being tested
Withholding PN during the first week of ICU stay, Oliclinomel N71000 OR N71000E // Clinimix N17G35 OR N17G35E
Keywords
early parenteral nutrition, critical illness, respiratory failure, kidney failure, hepatic failure, muscle strength, rehabilitation, overfeeding, Reduced Oral Intake
Medical subject headings
Critical Illness, Starvation, Hyperphagia, Respiratory Insufficiency, Renal Insufficiency, Liver Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Withholding PN during the first week of ICU stayOther

    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.

  • Oliclinomel N71000 OR N71000E // Clinimix N17G35 OR N17G35EDrug

    Also called Parenteral nutrition ATC code B05BA10

    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.

Study groups in NCT00512122
Study groupRoleWhat they receive
EN onlyExperimentalWithholding PN during the first week of ICU stay
Receives: Other: Withholding PN during the first week of ICU stay
EN plus early PNActive comparatorOliclinomel N71000 OR N71000E // Clinimix N17G35 OR N17G35E Parenteral nutrition targeted at covering calculated needs together with the enteral nutrition intake that is achieved
Receives: Drug: Oliclinomel N71000 OR N71000E // Clinimix N17G35 OR N17G35E

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 2 years

Secondary outcomes (14)

  1. Death (hospital and ICU mortality and 90 days mortality)

    Measured: 10 years

  2. Days to weaning from mechanical ventilation

    Measured: 2 years

  3. The need for renal replacement therapies

    Measured: 2 years

  4. The presence or absence of new kidney injury during intensive care

    Measured: 2 years

  5. Days of vasopressor or inotropic support

    Measured: 2 years

  6. The presence or absence of signs of ICU liver disease: hyperbilirubinemia (defined as bilirubin level > 3 mg/dl), presence of liversteatosis, sludge…

    Measured: 2 years

  7. The need for tracheotomy

    Measured: 2 years

  8. The presence or absence of hyper-inflammation within five days after ICU admission

    Measured: 2 years

  9. Blood lipid profiles and albumin on days one, five, ten, and fifteen after admission

    Measured: 2 years

  10. The presence or absence of bacteraemia, ventilator-associated pneumonia and of wound infections

    Measured: 2 years

  11. Episodes of hypoglycaemic events (defined as glycemia less than 40 mg/dl)

    Measured: 2 years

  12. Amount and type of calories delivered

    Measured: 2 years

  13. 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.

    Measured: 10 years

  14. 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.

    Measured: 10 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2007 (estimated)
  2. Study startAug 2007
  3. Primary completionFeb 2011
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Investigator
Enrolment
4,640 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00512122
Sponsor's protocol ID
EPaNIC 2007 1-2-2
Other IDs
ISRCTN 76223876, EudraCT 2007-000169-40, S 50404
Acronym
EPaNIC
Status last verified
Feb 2024
First submitted
31 Jul 2007
Last updated
12 Feb 2024
Results posted
No
Data monitoring committee
Yes

Publications

  • van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001 Nov 8;345(19):1359-67. doi: 10.1056/NEJMoa011300.

    PubMed 11794168

  • Uzun Ayar C, Derese I, Van den Berghe G, Vanhorebeek I. Epigenetic Aging of Critical Illness Survivors Assessed by the Muscle-Specific "Clock" and Its Relationship With Reduced Long-Term Muscle Strength. Aging Cell. 2026 Jul;25(7):e70629. doi: 10.1111/acel.70629.

    PubMed 42437371

  • Uzun Ayar C, Guiza F, Derese I, Pauwels L, Vander Perre S, Pintelon I, Casaer M, Van Aerde N, Hermans G, Derde S, Kreiss L, Van den Berghe G, Vanhorebeek I. Altered muscle transcriptome as molecular basis of long-term muscle weakness in survivors from critical illness. Intensive Care Med. 2025 Jun;51(6):1062-1077. doi: 10.1007/s00134-025-07949-3. Epub 2025 Jun 10.

    PubMed 40493222

  • Casaer MP, Stragier H, Hermans G, Hendrickx A, Wouters PJ, Dubois J, Guiza F, Van den Berghe G, Gunst J. Impact of withholding early parenteral nutrition on 2-year mortality and functional outcome in critically ill adults. Intensive Care Med. 2024 Oct;50(10):1593-1602. doi: 10.1007/s00134-024-07546-w. Epub 2024 Jul 17.

    PubMed 39017697

  • Van Dyck L, Guiza F, Derese I, Pauwels L, Casaer MP, Hermans G, Wouters PJ, Van den Berghe G, Vanhorebeek I. DNA methylation alterations in muscle of critically ill patients. J Cachexia Sarcopenia Muscle. 2022 Jun;13(3):1731-1740. doi: 10.1002/jcsm.12970. Epub 2022 Mar 11.

    PubMed 35274472

  • Vanhorebeek I, Derese I, Gunst J, Wouters PJ, Hermans G, Van den Berghe G. Persisting neuroendocrine abnormalities and their association with physical impairment 5 years after critical illness. Crit Care. 2021 Dec 16;25(1):430. doi: 10.1186/s13054-021-03858-1.

    PubMed 34915907

  • Ingels C, Langouche L, Dubois J, Derese I, Vander Perre S, Wouters PJ, Gunst J, Casaer M, Guiza F, Vanhorebeek I, Van den Berghe G. C-reactive protein rise in response to macronutrient deficit early in critical illness: sign of inflammation or mediator of infection prevention and recovery. Intensive Care Med. 2022 Jan;48(1):25-35. doi: 10.1007/s00134-021-06565-1. Epub 2021 Nov 24.

    PubMed 34816288

  • Van Aerde N, Meersseman P, Debaveye Y, Wilmer A, Gunst J, Casaer MP, Wauters J, Wouters PJ, Gosselink R, Van den Berghe G, Hermans G. Five-year outcome of respiratory muscle weakness at intensive care unit discharge: secondary analysis of a prospective cohort study. Thorax. 2021 Jun;76(6):561-567. doi: 10.1136/thoraxjnl-2020-216720. Epub 2021 Mar 12.

    PubMed 33712505

  • Van Dyck L, Gunst J, Casaer MP, Peeters B, Derese I, Wouters PJ, de Zegher F, Vanhorebeek I, Van den Berghe G. The clinical potential of GDF15 as a "ready-to-feed indicator" for critically ill adults. Crit Care. 2020 Sep 14;24(1):557. doi: 10.1186/s13054-020-03254-1.

    PubMed 32928255

  • Van Aerde N, Meersseman P, Debaveye Y, Wilmer A, Gunst J, Casaer MP, Bruyninckx F, Wouters PJ, Gosselink R, Van den Berghe G, Hermans G. Five-year impact of ICU-acquired neuromuscular complications: a prospective, observational study. Intensive Care Med. 2020 Jun;46(6):1184-1193. doi: 10.1007/s00134-020-05927-5. Epub 2020 Jan 22.

    PubMed 31970446

  • Hermans G, Van Aerde N, Meersseman P, Van Mechelen H, Debaveye Y, Wilmer A, Gunst J, Casaer MP, Dubois J, Wouters P, Gosselink R, Van den Berghe G. Five-year mortality and morbidity impact of prolonged versus brief ICU stay: a propensity score matched cohort study. Thorax. 2019 Nov;74(11):1037-1045. doi: 10.1136/thoraxjnl-2018-213020. Epub 2019 Sep 3.

    PubMed 31481633

  • Van Dyck L, Derese I, Vander Perre S, Wouters PJ, Casaer MP, Hermans G, Van den Berghe G, Vanhorebeek I. The GH Axis in Relation to Accepting an Early Macronutrient Deficit and Outcome of Critically Ill Patients. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5507-5518. doi: 10.1210/jc.2019-00842.

    PubMed 31361307

  • Thiessen SE, Derde S, Derese I, Dufour T, Vega CA, Langouche L, Goossens C, Peersman N, Vermeersch P, Vander Perre S, Holst JJ, Wouters PJ, Vanhorebeek I, Van den Berghe G. Role of Glucagon in Catabolism and Muscle Wasting of Critical Illness and Modulation by Nutrition. Am J Respir Crit Care Med. 2017 Nov 1;196(9):1131-1143. doi: 10.1164/rccm.201702-0354OC.

    PubMed 28475354

  • Flechet M, Guiza F, Schetz M, Wouters P, Vanhorebeek I, Derese I, Gunst J, Spriet I, Casaer M, Van den Berghe G, Meyfroidt G. AKIpredictor, an online prognostic calculator for acute kidney injury in adult critically ill patients: development, validation and comparison to serum neutrophil gelatinase-associated lipocalin. Intensive Care Med. 2017 Jun;43(6):764-773. doi: 10.1007/s00134-017-4678-3. Epub 2017 Jan 27.

    PubMed 28130688

  • Hermans G, Van Mechelen H, Bruyninckx F, Vanhullebusch T, Clerckx B, Meersseman P, Debaveye Y, Casaer MP, Wilmer A, Wouters PJ, Vanhorebeek I, Gosselink R, Van den Berghe G. Predictive value for weakness and 1-year mortality of screening electrophysiology tests in the ICU. Intensive Care Med. 2015 Dec;41(12):2138-48. doi: 10.1007/s00134-015-3979-7. Epub 2015 Aug 13.

    PubMed 26266842

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Withholding PN during the first week of ICU stay and Oliclinomel N71000 OR N71000E // Clinimix N17G35 OR N17G35E in people with Critical Illness and Starvation, run by KU Leuven at 3 sites in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 12 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Length of stay in ICU and length of stay in the hospital. (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00512122, which also lists 23 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2024.

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