Clinical trial NCT00522730: Safety and Tolerance on Lipids of Parenteral and Enteral Nutrition in Critically Ill Patients With Liver Failure
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Liver Failure
Critical Illness
Keywords: Liver failure
Liver cirrhosis
Parenteral nutrition
Enteral nutrition
Lipids
Safety
Drug tolerance
Lead sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sponsor class: OTHER
First posted: 2007-08-30
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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%.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in plasma concentration of triglycerides, total cholesterol, HDL-cholesterol, free fatty acids, apolipoproteins, lipoprotein (a)
timeFrame: within 5 days
Secondary outcomes:
measure: Incidence of hyperglycaemia
timeFrame: within 5 days
measure: Alteration of liver function
timeFrame: within 5 and 28 days
measure: Gastrointestinal intolerance
timeFrame: within 5 days
measure: Gastrointestinal bleeding
timeFrame: within 5 and 28 days
measure: Septic complications
timeFrame: within 5 and 28 days
measure: Occurence of new organ dysfunction
timeFrame: within 5 and 28 days
measure: Length of stay in the intensive care unit (ICU)
timeFrame: within 5 and 28 days
measure: Mortality
timeFrame: within 5 and 28 days
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Departement of intensive care, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain
Study officials:
affiliation: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
name: Pierre-François Laterre, MD
role: STUDY_DIRECTOR
affiliation: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
name: Yvan Fleury, MD
role: PRINCIPAL_INVESTIGATOR
References: