Influence of Early vs Late SPN on Long-term Quality of Life in ICU Patients After Gastrointestinal Oncological Surgery (hELPLiNe)

Influence of Early vs Late Supplemental ParenteraL Nutrition on Long-term Quality of Life in ICU Patients After Gastrointestinal Oncological Surgery. A Prospective, Randomised, Multi-centre Assessor-blinded Study. hELPLiNe Trial

BACKGROUND: Nutrition plays a significant role in ICU treatment, and may influence mortality and length of stay in ICU. Enteral route (EN) is preferential to parenteral route (PN) in provision of daily nutritional requirements. When enteral route is insufficient, supplemental parenteral nutrition (SPN) is recommended. Optimal timing of SPN in acute phase of illness remains elusive. ICU patients suffer significant lean body mass loss, in majority, in the first 7-10 days of stay. Optimal provision of protein may prevent muscle wasting. Lean body mass is essential for optimal physical functioning after treatment. Although ICU mortality has been reduced lately, the number of patients going to rehabilitation after ICU stay has tripled. Patients after oncological surgery of the gastrointestinal tract may be threatened with impairment of physical functioning after ICU treatment.

AIM: To compare the influence of early and late supplemental parenteral nutrition on long-term physical functioning in ICU patients after oncological surgery of the gastrointestinal tract.

STUDY DESIGN: Prospective, randomised, multi-centre assessor-blinded study. METHODS & ANALYSIS: Patients will be randomised into intervention group that would receive SPN on first day, and would be continued until 7th day of stay in ICU. Control group would receive SPN on 7th day of stay in ICU, when it is not then already met via enteral route. Physical Component of SF-36 Scale at 6 month after ICU admission will be assessed.

Study Overview

• Status: Unknown
• Conditions: Nutrition Aspect of Cancer
• Intervention / Treatment: Procedure: Early Supplemental Parenteral Nutrition

• Study Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-059
      • 2nd Department of Anesthesiology and Critical Care, Medical University of Lublin
  • Silesia
    • Opole, Silesia, Poland, 45-401
      • Department of Anesthesiology and Intensive Care, Uniwersytecki Szpital Kliniczny w Opolu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ICU patients in the acute phase of critical illness after gastrointestinal oncological surgery.
2. Admitted to the ICU during the previous 24 hours with a minimum expected ICU stay of ≥5 days
3. Central venous access available for continuous infusion of the study drugs
4. Sequential Organ Failure Assessment (SOFA) score ≥2
5. Written informed consent from the patient or the patient's legal representative

Exclusion Criteria:

Contraindication against SPN or inability to receive SPN via central venous access

1. Received PN within 7 days before randomisation
2. Expected to receive ≥20% of energy via supplemental enteral nutrition (EN) and/or non-nutritional sources (e.g. glucose solution for drug dilution or lipids from propofol) during the first 3 nutritional treatment days
3. Inability to initiate EN prior to randomization
4. Body mass index (BMI) <17 kg/m2 or >35 kg/m2
5. Any severe, persistent blood coagulation disorder with uncontrolled bleeding
6. Any congenital errors of amino acid metabolism
7. Known hypersensitivity to fish, egg, soybean proteins, peanut proteins, or to any of the active substances or excipients contained in SPN.
8. Known hypersensitivity to milk protein or to any other substance contained in SPN
9. Acute liver failure with encephalopathy, including intoxication (e.g. paracetamol, death cap, golden chain) and/or liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma glutamyl transferase [GGT]) or bilirubin exceeding 10 x ULN
10. Hemophagocytic syndrome
11. Known history of human immunodeficiency virus (HIV), hepatitis B and/or C
12. Pregnancy or lactation
13. Patient unlikely to survive to 6 months due to underlying illness

14. Receiving end-of-life-care

    Laboratory Exclusions:

15. Hypertriglyceridemia characterised by serum triglyceride levels >4 mmol/L [>350 mg/dL])

16. Treatment-refractory, clinically significant major abnormality in the serum concentration of any electrolyte (sodium, potassium, magnesium, total calcium, chloride, inorganic phosphate)

    Concomitant Therapy Exclusions:

17. Chronic maintenance therapy with systemic glucocorticoid steroids (Hydrocortisone >0.3 mg/kg/d)
18. Concomitant administration of chemotherapy

19. Administration of growth hormone and teduglutide within the previous 4 weeks

    Other Exclusions:

20. Chronic liver failure ( Child -Pugh scale B or C) e.g. secondary to drug or alcohol abuse
21. Participation in another interventional clinical trial within the previous 4 weeks
22. Previous inclusion in the present study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early Supplemental Parenteral Nutrition; Intervention group: would receive EN reaching up to 20 % of daily nutritional requirements and early (on first day of stay in ICU) provision (of up to 80%) of protein (2 g/kg/ day or in case of continuous renal replacement therapy (CRRT) 2,5 g/kg/ day) and caloric (15-20 kcal/kg/day) needs in SPN that would be continued until 7th day of stay in ICU for the purpose of the study.	Procedure: Early Supplemental Parenteral Nutrition; Intervention group: would receive EN reaching up to 20 % of daily nutritional requirements and early (on first day of stay in ICU) provision (of up to 80%) of protein (2 g/kg/ day or in case of CRRT 2,5 g/kg/ day) and caloric (15-20 kcal/kg/day) needs in SPN that would be continued until 7th day of stay in ICU. Central venous catheter placement would not be assessed as a part of intervention due to the fact that it is a part of routine medical activities performed during admission to ICU.
No Intervention: Late Supplemental Parenteral Nutrition; Control group: would receive EN reaching up to 20 % of daily nutritional requirements and late (of up to 80%) of protein (2 g/kg/ day or in case of CRRT 2,5 g/kg/ day) and caloric (15-20 kcal/kg/day ) in SPN on 7th day of stay in ICU if it is not already met via enteral route.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term quality of life at 3 months	Long-term quality of life measured in physical component of 36 -SF questionnaire	Physical component of 36 -SF questionnaire at 3 months after admission to ICU
Long-term quality of life at 6 months	Long-term quality of life measured in physical component of 36 -SF questionnaire	Physical component of 36 -SF questionnaire at 6 months after admission to ICU

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Enteral route intolerance	Inability to administer up to 60% of protein needs on 3rd day via enteral route	At day 3 since admission to ICU
Thickness of diaphragm	Change from baseline in ultrasound measured thickness of diaphragm	1st, 3rd, 5th day of ICU stay
Protein delivery	Protein delivery defined as daily input of proteins via SPN	For 7 days since admission to ICU
Energy Intake	Energy delivery defined as daily input of calories via SPN	For 7 days since admission to ICU
Insulin dose	Insulin dose defined as summary daily input of insulin	For 7 days since admission to ICU
Blood glucose profile	Blood glucose profile defined as mean daily glucose level	For 7 days since admission to ICU
Organic phosphorus level	Organic phosphorus level defined as result in blood test performed daily	For 7 days since admission to ICU
Sequential Organ Failure Assessment score ( SOFA score)	We will collect data regarding changes from baseline SOFA score - to determine the extent of a person's organ function failure. SOFA scoring system is useful in predicting the clinical outcomes of critically ill patients. Patient can be scored from 0 to 24. If the patient is scored 0 than the patient is in a good state and predicted mortality is low, while 24 is the worst result with expected very high mortality rate.	For 28 days since admission to ICU or till discharge
Mechanical Ventilation	Numbers of days of mechanical ventilation	For 28 days since admission to ICU or till discharge
Length of stay in the ICU	Numbers of days of patient stay in ICU	For 28 days since admission to ICU or till discharge
ICU mortality		For 28 days since admission to ICU or till discharge
Hospital mortality		For 28 days since admission to ICU or till discharge
Length of stay in hospital	Numbers of days of patient stay in hospital	For 28 days since admission to ICU or till discharge
Health-care associated infection	New onset of health-care associated infection	For 28 days since admission to ICU or till discharge
Antibiotic-free days	Number of days patient was not given the antibiotics	For 28 days since admission to ICU or till discharge

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PCS SF-36 change	Change from baseline in PCS SF-36	From enrollment till 6 months assessment

Collaborators and Investigators

• Sponsor: Medical University of Lublin
• Collaborators: Uniwersytecki Szpital Kliniczny w Opolu
• Investigators: Principal Investigator: Paweł Piwowarczyk, MD PhD, Medical University in Lublin

Publications and helpful links

General Publications

• Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, Hopkinson NS, Phadke R, Dew T, Sidhu PS, Velloso C, Seymour J, Agley CC, Selby A, Limb M, Edwards LM, Smith K, Rowlerson A, Rennie MJ, Moxham J, Harridge SD, Hart N, Montgomery HE. Acute skeletal muscle wasting in critical illness. JAMA. 2013 Oct 16;310(15):1591-600. doi: 10.1001/jama.2013.278481. Erratum In: JAMA. 2014 Feb 12;311(6):625. Padhke, Rahul [corrected to Phadke, Rahul].
• Nicolo M, Heyland DK, Chittams J, Sammarco T, Compher C. Clinical Outcomes Related to Protein Delivery in a Critically Ill Population: A Multicenter, Multinational Observation Study. JPEN J Parenter Enteral Nutr. 2016 Jan;40(1):45-51. doi: 10.1177/0148607115583675. Epub 2015 Apr 21.
• Sundstrom Rehal M, Liebau F, Tjader I, Norberg A, Rooyackers O, Wernerman J. A supplemental intravenous amino acid infusion sustains a positive protein balance for 24 hours in critically ill patients. Crit Care. 2017 Dec 6;21(1):298. doi: 10.1186/s13054-017-1892-x.
• Arends J, Bachmann P, Baracos V, Barthelemy N, Bertz H, Bozzetti F, Fearon K, Hutterer E, Isenring E, Kaasa S, Krznaric Z, Laird B, Larsson M, Laviano A, Muhlebach S, Muscaritoli M, Oldervoll L, Ravasco P, Solheim T, Strasser F, de van der Schueren M, Preiser JC. ESPEN guidelines on nutrition in cancer patients. Clin Nutr. 2017 Feb;36(1):11-48. doi: 10.1016/j.clnu.2016.07.015. Epub 2016 Aug 6.
• Allingstrup MJ, Kondrup J, Wiis J, Claudius C, Pedersen UG, Hein-Rasmussen R, Bjerregaard MR, Steensen M, Jensen TH, Lange T, Madsen MB, Moller MH, Perner A. Early goal-directed nutrition versus standard of care in adult intensive care patients: the single-centre, randomised, outcome assessor-blinded EAT-ICU trial. Intensive Care Med. 2017 Nov;43(11):1637-1647. doi: 10.1007/s00134-017-4880-3. Epub 2017 Sep 22.
• Reignier J, Boisrame-Helms J, Brisard L, Lascarrou JB, Ait Hssain A, Anguel N, Argaud L, Asehnoune K, Asfar P, Bellec F, Botoc V, Bretagnol A, Bui HN, Canet E, Da Silva D, Darmon M, Das V, Devaquet J, Djibre M, Ganster F, Garrouste-Orgeas M, Gaudry S, Gontier O, Guerin C, Guidet B, Guitton C, Herbrecht JE, Lacherade JC, Letocart P, Martino F, Maxime V, Mercier E, Mira JP, Nseir S, Piton G, Quenot JP, Richecoeur J, Rigaud JP, Robert R, Rolin N, Schwebel C, Sirodot M, Tinturier F, Thevenin D, Giraudeau B, Le Gouge A; NUTRIREA-2 Trial Investigators; Clinical Research in Intensive Care and Sepsis (CRICS) group. Enteral versus parenteral early nutrition in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group study (NUTRIREA-2). Lancet. 2018 Jan 13;391(10116):133-143. doi: 10.1016/S0140-6736(17)32146-3. Epub 2017 Nov 8.
• Piwowarczyk P, Kutnik P, Borys M, Rypulak E, Potrec-Studzinska B, Sysiak-Slawecka J, Czarnik T, Czuczwar M. Influence of Early versus Late supplemental ParenteraL Nutrition on long-term quality of life in ICU patients after gastrointestinal oncological surgery (hELPLiNe): study protocol for a randomized controlled trial. Trials. 2019 Dec 27;20(1):777. doi: 10.1186/s13063-019-3796-3.

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2018
• Primary Completion (Anticipated): November 1, 2020
• Study Completion (Anticipated): May 1, 2021

Study Registration Dates

• First Submitted: October 4, 2018
• First Submitted That Met QC Criteria: October 5, 2018
• First Posted (Actual): October 9, 2018

Study Record Updates

• Last Update Posted (Actual): October 12, 2018
• Last Update Submitted That Met QC Criteria: October 11, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: critical care; quality of life; early parenteral nutrition; supplemental nutrition; oncological surgery
• Other Study ID Numbers: KE-0254/152/2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No