ICULIP, Influence of Two Lipid Emulsions in the Nosocomial Infection in Critical Patients

Condition(s) targeted: Critical Illness

Intervention: MCT/LCT (1:1) (Drug); MCT/LCT/omega-3 (5:4:1) (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: B. Braun Medical SA

Official(s) and/or principal investigator(s):
Abelardo García de Lorenzo, MD, Study Chair, Affiliation: Hospital Universitario La Paz (Madrid)
Alfonso Bonet Saris, MD_Study Coordinator, Principal Investigator, Affiliation: Hospital Universitari de Girona Doctor Josep Trueta
Teodoro Grau Carmona, MD_Study Coordinator, Study Chair, Affiliation: Hospital Severo Ochoa Leganés (Madrid)

Overall contact:
Jaume Jané Pujol, Product & Study Manager, Phone: +34-93.586.64.18, Email: jaume.jane_pujol@bbraun.com

This study aims to analyse the effect of two total parenteral nutrition diets with lipid emulsions of different compositions on the incidence of nosocomial infection in critical patients. One diet will contain an MCT/LCT emulsion concentrated to 20% (50: 50 ratio) and the other will comprise an MCT/LCT/fish oil emulsion (50: 40: 10 ratio). The secondary objective of this study is to analyse mortality in hospital and up to 6 months of discharge.

Official title: Phase IV-IV. ICULIP,a Prospective,Multi-Centre,Randomised,Comparative,Double-Blind Study to Evaluate Two Different Types of Lipid Emulsions Used for Total Parenteral Nutrition in Critical Patients and Their Influence on Nosocomial Infection.

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Efficacy Study

Primary outcome:

The analyses will particularly focus on: Pneumonia associated with mechanical ventilation, Catheter infection, Bacteraemia not associated with catheter, Urinary infection, Infection of surgical wounds and Intra-abdominal abscess and peritonitis.

Compare the incidence of nosocomial infection associated with the administration of two different lipid solutions in total parenteral nutrition of patients in an Intensive Care Unit.

Secondary outcome: Study mortality at the end of the study and 6 months after discharge from ICU; Hospital stay and/or in Intensive Care Unit; Mechanical ventilation days; Assessment of hepatic function; Assessment of nutritional efficacy.

Detailed description: During the last years the most widely used lipid emulsion for parenteral nutrition has been based on soybean oil. This first generation of lipid emulsions used in TPN contained w-6 series polyunsaturated long-chain fatty acids (LCT) from soy, maize, sunflower and safflower oil. LCT contain an excess of linoleic acid which, when metabolised, produce large quantities of arachidonic acid and its metabolites. Although the generally used doses seem safe (1-2 g/kg/day by continuous perfusion), alterations in pulmonary function in patients with acute adult respiratory distress syndrome have been described, as have alterations in platelet function, hepatic function and haemodynamics, which are attributed to the excess of said metabolites. However, the most important side effect of the LCT lipid infusions is its influence on the immune response. Experimental and clinical studies show that LCT can interfere with various stages of the immune response such as the production of antibodies, complement synthesis, granulocytic and lymphocytic activity and the reticuloendothelial system. Various hypotheses have been formulated to explain the modulator effect of the polyunsaturated fatty acids on immune function: changes in the permeability of the cellular membrane, modifications in the synthesis of eicosanoids and the presence of peroxides derived from the oxidation of polyunsaturated fatty acids.

In summary, although linoleic acid as a dietary essential fatty acid is important, its excessive intake is associated with undesirable immunological and inflammatory events. Thus it is recommended that soybean oil should be partly replaced by other lipids.

To avoid these side effects the second generation lipid emulsions were developed. These contain a combination of medium- and long-chain fatty acids (MCT/LCT) with lower w-6 fatty acid content. MCT/LCT lipid emulsions are safe and do not produce biochemical or metabolic alterations or gaseous exchange in patients with ARDS. MCT/LCT combinations seem to reduce the generation of eicosanoids and do not alter the immune response in in-vitro and experimental studies. The impact of these differences on the nosocomial infection and the clinical prognosis of the patients has not been studied sufficiently despite the fact that some studies show reduced mortality and morbidity using MCT/LCT emulsions when compared with the use of pure LCT emulsions. MCT/LCT emulsions are normally used in clinical practice on patients that have required parenteral nutrition for 20 years.

Recently, the clinical use in artificial nutrition of omega-3 series polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) present in many fish oils has been significant. EPA is a precursor to certain eicosanoid series that compensate the proinflammatory effects of the eicosanoids in arachidonic acid (omega-6 series). The objective is immunomodulation to attenuate the inflammatory response of patients without negatively impacting on the immune function. The use of enteral diets enriched with omega-3 series fatty acids (fish oil) in post-operation cancer patients showed a reduction in the number of days in hospital and infectious complications.

The use of fish oil or fat emulsions enriched with fish oil (omega-3) in parenteral nutrition has already been the subject of various studies: where modulation of the inflammatory response markers has been shown, reduces the stay in hospital and the need for mechanical ventilation in patients undergoing major abdominal surgery, reduces the stay in hospital in patients undergoing digestive surgery… So, w-3 lipids exhibit strong immunologic properties. They offer the possibility to counterbalance the negative effects of conventional w-6 fatty acids. Recent studies exhibit positive effects of intravenous use of fish oil on immunologic functions and clinical parameters in surgical and septic patients

The purpose of this study is to analyse the effect of two total parenteral nutrition diets with lipid emulsions of different compositions on the incidence of nosocomial infection in critical patients. One diet will contain an MCT/LCT emulsion concentrated to 20% (50: 50 ratio) (w3: w6 is 1: 7) and the other will comprise an MCT/LCT/fish oil emulsion (50: 40: 10 ratio) (w3: w6 is 1: 2,7). The secondary objective of this study is to analyse mortality in hospital and up to 6 months after discharge.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

INCLUSION CRITERIA:

Patients of both sexes, prospective admission to Intensive Care Units (ICUs), over 18 years, where TPN is required as a nutritional metabolic support for a minimum period of 5 days and where said patients have signed the informed consent form.

The indications for administration of parenteral nutrition shall be those recommended by the American Society of Parenteral and Enteral Nutrition (ASPEN), and in particular:

- Severe malnutrition

- Major intra-abdominal surgery

- Peritonitis

- Intestinal ischaemia

- Intestinal occlusion

- Gastrointestinal fistulas

- Small intestine

Patients of both sexes, over 18 years, that commencing nutritional support with enteral diets in the first 3 days of admission to ICU require parenteral nutrition as:

- 75% of the calculated energy requirements have not been reached after three days

receiving enteral nutrition.

- Gastrointestinal complications have been suffered as a result of enteral nutrition

that cannot be treated or are persistent in the first 3 days of admission.

In this case EN will be suspended and the patient will be included in the protocol receiving PN.

EXCLUSION CRITERIA:

- APACHE II < 13

- Morbid obesity (BMI ≥ 39)

- Hepatic disease defined within the following set of parameters:

1. Portal hypertension with gastrointestinal bleeding on admission

2. Clinically apparent hepatocellular ascites

3. Hepatocellular bilirubin higher than 3 mg/dL

4. Serum albumin less than 30 g/L with portal hypertension

5. Grade II or higher encephalopathy

6. Clinical diagnosis of alcoholic hepatitis

- Chronic renal insufficiency defined by one of the following criteria:

1. Plasmatic creatinine greater than 4 mg/dL

2. Chronic peritoneal dialysis or haemodialysis

- Patients with severe acquired or familial hyperlipidaemias (> 400 mg/day) of any kind

- Serious chronic neurological disease defined by one of the following criteria:

1. Cerebrovascular accident with persistent neurological deficit in the past six months

2. Neurological deficit that necessitates chronic confinement

- Neoplastic patients with metastasis and a life expectancy of less than six months

- Patients that underwent chemotherapy or radiotherapy during the month prior to the

study

- Patients that received chronic treatment with corticoids in the month preceding

admission to ICU. Patients receiving treatment with corticoids since admission to ICU for septic shock should not be excluded.

- Continuous infusion treatment for more than 24 hours with propofol or with other

pharmaceuticals where lipid emulsions are used as the vehicle

- Infectious diseases transmitted through the blood, products derived from blood or

urine: hepatitis B, C and HIV

- Inclusion in another clinical trial

- Having received TPN in the month prior to inclusion in the study

- Pregnancy

- Refusal to participate in the study

Jaume Jané Pujol, Product & Study Manager, Phone: +34-93.586.64.18, Email: jaume.jane_pujol@bbraun.com

Hospital General Universitario de Alicante, Alicante 03010, Spain; Recruiting
José Acosta Escribano, MD, Phone: +34-965.93.83.00, Email: acosta_jos@telefonica.net
José Acosta Ecribano, MD, Principal Investigator

Hospital del Mar (Institut Municipal d'Assistència Sanitària, IMAS), Barcelona 08003, Spain; Recruiting
Inmaculada Albert, MD, Phone: +34-93.248.30.14, Email: ialbert@imas.imim.es
Inmaculada Albert, MD, Principal Investigator

Hospital Universitari Vall d'Hebrón, Barcelona 08035, Spain; Recruiting
Mercè Planas, MD, Phone: +34-93.274.62.62, Email: mplanas@vhebron.net
Mercè Planas, MD, Principal Investigator

Hospital Universitario "Puerta del Mar", Cádiz 11009, Spain; Recruiting
Lucas Picazo Soto, MD, Phone: +34-956.00.21.00, Email: lpicazo@telefonica.net
Lucas Picazo Soto, MD, Principal Investigator

Hospital Universitari de Girona Doctor Josep Trueta, Girona 17007, Spain; Recruiting
Alfons Bonet Saris, MD_Study Coordinator, Phone: +34-972.940.200, Email: uci.abonet@htrueta.scs.es
Alfons Bonet Saris, MD_Study Coordinator, Principal Investigator

Hospital Universitario Virgen de las Nieves, Granada 18014, Spain; Recruiting
José Castaño Pérez, MD, Phone: +34-958.02.00.00, Email: antonioj.perez.sspa@juntadeandalucia.es
José Castaño Pérez, MD, Principal Investigator

Fundación Jiménez Díaz, Madrid 28040, Spain; Not yet recruiting
Paloma González, MD, Phone: +34-91.550.49.67, Email: pgonzalez@fjd.es
Paloma González, MD, Principal Investigator

Hospital General Universitario "Reina Sofía", Murcia 30003, Spain; Recruiting
Carmen Sánchez, MD, Phone: +34-968.35.90.00, Email: carmen.sanchez6@carm.es
Carmen Sánchez, MD, Principal Investigator

Hospital Regional Universitario Carlos Haya, Málaga 29010, Spain; Recruiting
Francisco Fernández Ortega, MD, Phone: +34-95.239.05.00, Email: patferon@eresmas.com
Francisco Fernández Ortega, MD, Principal Investigator

Hospital Universitario de Valme, Sevilla 41014, Spain; Not yet recruiting
José A. Irles, MD, Phone: +34-95.501.50.00, Email: josea.irles.sspa@juntadeandalucia.es
José A. Irles, MD, Principal Investigator

Hospital Clínico Universitario de Valencia, Valencia 46010, Spain; Recruiting
Alfonso Mesejo, MD, Phone: +34-963.86.26.00, Email: mesejo_alf@gva.es
Alfonso Mesejo, MD, Principal Investigator

Hospital Universitario Del Río Hortega, Valladolid 47010, Spain; Not yet recruiting
Luis A. Dominguez, MD, Phone: +34-983.42.04.00, Email: ldominguez@hurh.sacyl.es
Luis A. Dominguez, MD, Principal Investigator

Hospital Son Dureta, Palma de Mallorca, Baleares 07014, Spain; Not yet recruiting
Pedro Marsé, MD, Phone: +34-971.17.50.00, Email: pmarse@telefonica.net
Pedro Marsé, MD, Principal Investigator

Hospital Universitario de Bellvitge (H.U.B.), Hospitalet de Llobregat, Barcelona 08097, Spain; Recruiting
José I. Herrero Meseguer, MD, Phone: +34-93.260.75.11, Email: jiherrero@csub.scs.es
José I. Herrero Meseguer, MD, Principal Investigator

Hospital Universitario Marqués de Valdecilla, Santander, Cantabria 39008, Spain; Recruiting
Javier Ordóñez González, MD, Phone: +34-942.20.25.20, Email: javier.ordonez@telefonica.net
Javier Ordóñez González, MD, Principal Investigator

Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Gran Canaria 35010, Spain; Recruiting
Sergio Ruiz Santana, MD, Phone: +34-928.45.06.73, Email: sruisan@gobiernodecanarias.org
Sergio Ruiz Santana, MD, Principal Investigator

Complejo Hospitalario Materno Insular de Gran Canaria, Las Palmas de Gran Canaria, Gran Canaria 35016, Spain; Recruiting
Manuel Sánchez Palacios, MD, Phone: +34-928.44.13.92, Email: msanpal@gobiernodecanarias.org
Manuel Sánchez Palacios, MD, Principal Investigator

Hospital Severo Ochoa, Leganés, Madrid 28911, Spain; Not yet recruiting
Jorge López Martínez, MD, Phone: +34-91.481.80.00, Email: jlopezm.hsvo@salud.madrid.org
Jorge López Martínez, MD, Principal Investigator

Hospital Universitario "Virgen de la Arrixaca", El Palmar, Murcia 30120, Spain; Recruiting
Rafael Nuñez Ruiz, MD, Phone: +34-968.36.95.00, Email: rafanr@telefonica.net
Rafael Nuñez Ruiz, MD, Principal Investigator

Spanish Society for Parenteral and Enteral Nutrition

ASPEN, American Society for Parenteral and Enteral Nutrition --> Nutrition-related Links

Spanish Society for Intensive Medicine, Critical and Coronary Units

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Starting date: November 2006
Ending date: September 2008
Last updated: April 24, 2008