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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Nutrition Aspect of Cancer

Intervention / Treatment
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* Procedure: Early Supplemental Parenteral Nutrition


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ICU patients in the acute phase of critical illness after gastrointestinal oncological surgery. Admitted to the ICU during the previous 24 hours with a minimum expected ICU stay of ≥5 days Central venous access available for continuous infusion of the study drugs Sequential Organ Failure Assessment (SOFA) score ≥2 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 Received PN within 7 days before randomisation 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 Inability to initiate EN prior to randomization Body mass index (BMI) <17 kg/m2 or >35 kg/m2 Any severe, persistent blood coagulation disorder with uncontrolled bleeding Any congenital errors of amino acid metabolism Known hypersensitivity to fish, egg, soybean proteins, peanut proteins, or to any of the active substances or excipients contained in SPN. Known hypersensitivity to milk protein or to any other substance contained in SPN 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 Hemophagocytic syndrome Known history of human immunodeficiency virus (HIV), hepatitis B and/or C Pregnancy or lactation Patient unlikely to survive to 6 months due to underlying illness Receiving end-of-life-care Laboratory Exclusions: Hypertriglyceridemia characterised by serum triglyceride levels >4 mmol/L [>350 mg/dL]) Treatment-refractory, clinically significant major abnormality in the serum concentration of any electrolyte (sodium, potassium, magnesium, total calcium, chloride, inorganic phosphate) Concomitant Therapy Exclusions: Chronic maintenance therapy with systemic glucocorticoid steroids (Hydrocortisone >0.3 mg/kg/d) Concomitant administration of chemotherapy Administration of growth hormone and teduglutide within the previous 4 weeks Other Exclusions: Chronic liver failure ( Child -Pugh scale B or C) e.g. secondary to drug or alcohol abuse Participation in another interventional clinical trial within the previous 4 weeks Previous inclusion in the present study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: prospective, randomised, multi-centre assessor-blinded study
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early Supplemental Parenteral Nutrition<br>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<br>* 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.<br>|
| No Intervention: Late Supplemental Parenteral Nutrition<br>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?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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early parenteral nutrition, supplemental nutrition, quality of life, oncological surgery, critical care