Safety and Tolerance on Lipids of Parenteral and Enteral Nutrition in Critically Ill Patients With Liver Failure (SELLIFA)

Sepsis, Endothelial Function, and Lipids in Critically Ill Patients With Liver Failure (SELLIFA). Randomized Controlled Trial Comparing the Tolerance on Lipids and Safety of Isocaloric Parenteral Nutrition With Enteral Nutrition.

The purpose of the study is to determine the tolerance on lipid metabolism and the safety of short-term parenteral nutrition as compared to enteral nutrition in critically ill patients with liver failure.

Study Overview

• Status: Completed
• Conditions: Liver Failure; Critical Illness
• Intervention / Treatment: Other: Parenteral nutrition; Other: Enteral nutrition

Detailed Description

An impaired lipid metabolism is often found in patients with liver disease and is assumed to influence the prognosis. The central role of lipid metabolism in the pathophysiology of fatty liver disease and steatohepatitis is well established. In cirrhotic patients, serum lipid levels are mostly decreased and related to the severity of liver failure; in addition, the structure and composition of lipoproteins differ from that of healthy individuals. A reduction in high-density lipoproteins has been associated with higher cytokines levels and a poorer clinical outcome in septic patients. Furthermore, the oxidative stress induced by septic complications in critically ill patients with liver failure may lead to further hepatocellular injury and activation of systemic inflammation cascade.

In this setting, the influence of nutrition on lipid metabolism may have an impact on the severity of liver failure and associated complications. Although plasma clearance and oxidation of lipids were considered to be normal in the majority of patients with cirrhosis, most previous studies only reported the effects of an oral ingestion or parenteral infusion of lipids during a few hours.

The present randomized controlled trial will be conducted in a subgroup of patients enrolled in the SELLIFA-01 prospective study (NCT00488917). The purpose of the nutritional trial is to determine the tolerance on lipid metabolism and the safety of isocaloric short-term parenteral nutrition as compared to enteral nutrition in critically ill septic and non septic patients with liver failure. The nutrition will be delivered continuously for 5 days and will provide a daily energy supply corresponding to current resting energy expenditure as determined by indirect calorimetry, with 35% of total energy requirements as lipids, 15% as proteins (maximum 1.2g/kg ideal body weight/day), and 50% as dextrose. A tight glucose control strategy will be implemented to avoid hyperglycemia.

The trial is designed to randomly assign 15 patients in each interventional group in order to detect more than 25% increase in plasma triglycerides levels with 80% statistical power for two-tailed type I error of 5%.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Departement of intensive care, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All consecutive patients with a diagnosis of chronic liver failure;
• Planned total nutritional support;
• Adult patient aged 18 years or above, and less than 85;
• Admission to the ICU for an expected period of > 24 hours;
• Informed consent of the patient or nearest relative.

Exclusion Criteria:

• Absolute contra-indications to enteral nutrition : total mechanical ileus, persistent vomiting, high output fistulas, uncertain gastrointestinal anastomosis;
• Absolute contra-indications to parenteral nutrition : severe hypertriglyceridemia > 6 mmol/l (> 545 mg/dL), severe diabetic ketoacidosis;
• Age less than 18 years or more than 85;
• Pregnancy, including HELLP syndrome;
• Active malignancy with metastases (localized hepatocellular carcinoma is not an exclusion criteria);
• Systemic chemotherapy in the last 4 weeks (trans-arterial chemo-embolisation for localized hepatocellular carcinoma is not an exclusion criteria);
• Acquired immunodeficiency syndrome and antiretroviral therapy;
• Refusal of the patient or nearest relative.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Parenteral nutrition	Other: Parenteral nutrition; Duration : 5 days
Active Comparator: 2; Enteral nutrition	Other: Enteral nutrition; Duration : 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in plasma concentration of triglycerides, total cholesterol, HDL-cholesterol, free fatty acids, apolipoproteins, lipoprotein (a)	within 5 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of hyperglycaemia	within 5 days
Alteration of liver function	within 5 and 28 days
Gastrointestinal intolerance	within 5 days
Gastrointestinal bleeding	within 5 and 28 days
Septic complications	within 5 and 28 days
Occurence of new organ dysfunction	within 5 and 28 days
Length of stay in the intensive care unit (ICU)	within 5 and 28 days
Mortality	within 5 and 28 days

Collaborators and Investigators

• Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Investigators: Principal Investigator: Yvan Fleury, MD, Cliniques universitaires Saint-Luc- Université Catholique de Louvain; Study Director: Pierre-François Laterre, MD, Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: August 29, 2007
• First Submitted That Met QC Criteria: August 29, 2007
• First Posted (Estimate): August 30, 2007

Study Record Updates

• Last Update Posted (Estimate): September 3, 2009
• Last Update Submitted That Met QC Criteria: September 2, 2009
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: Safety; Lipids; Liver cirrhosis; Liver failure; Parenteral nutrition; Enteral nutrition; Drug tolerance
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease Attributes; Liver Diseases; Liver Failure; Hepatic Insufficiency; Critical Illness
• Other Study ID Numbers: SELLIFA-02; B40320072194; EudraCT n°2007-002940-86