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

Sponsor
B. Braun Medical SA (Industry)
Overall Status
Terminated
CT.gov ID
NCT00396461
Collaborator
(none)
212
Enrollment
22
Locations
2
Arms
51
Duration (Months)
9.6
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: MCT/LCT (1:1)
  • Drug: MCT/LCT/omega-3 (5:4:1)
 Phase 4

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
212 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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 Start Date :
Nov 1, 2006
Actual Primary Completion Date :
Sep 1, 2010
Actual Study Completion Date :
Feb 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: TPN A (Group I)

Emulsion based on 20% MCT/LCT (50:50 ratio)

Drug: MCT/LCT (1:1)
Emulsion based on 20% MCT/LCT (50:50 ratio)
Other Names:
  • LIPOFUNDINA

    		•
    Experimental: TPN B (Group II)

    Emulsion based on 20% MCT/LCT/w3 (50:40:10 ratio), medium- and long-chain triglycerides and fish oil triglycerides

    Drug: MCT/LCT/omega-3 (5:4:1)
    Emulsion based on 20% MCT/LCT/w3 (50:40:10 ratio), medium- and long-chain triglycerides and fish oil triglycerides.
    Other Names:
  • LIPOPLUS

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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. [Patients will receive at least 5 days of PN. Clinical condition and nosocomial infection will be monitored daily until the first phase of the study is completed on day 28 or the patient is discharged from the unit.]

    2. 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. [Patients will receive at least 5 days of PN. Clinical condition and nosocomial infection will be monitored daily until the first phase of the study is completed on day 28 or the patient is discharged from the unit.]

    Secondary Outcome Measures

    1. 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. [At the end of the study and 6 months after discharge from ICU.]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Hospital Son Dureta Palma de Mallorca Baleares Spain 07014
    2 Hospital Universitario de Bellvitge (H.U.B.) Hospitalet de Llobregat Barcelona Spain 08097
    3 Hospital de Cruces Barakaldo Bizcaya Spain 48903
    4 Hospital Universitario Marqués de Valdecilla Santander Cantabria Spain 39008
    5 Hospital Universitario de Gran Canaria Dr. Negrín Las Palmas de Gran Canaria Gran Canaria Spain 35010
    6 Complejo Hospitalario Materno Insular de Gran Canaria Las Palmas de Gran Canaria Gran Canaria Spain 35016
    7 Hospital Severo Ochoa Leganés Madrid Spain 28911
    8 Hospital Universitario "Virgen de la Arrixaca" El Palmar Murcia Spain 30120
    9 Hospital General Universitario de Alicante Alicante Spain 03010
    10 Hospital del Mar (Institut Municipal d'Assistència Sanitària, IMAS) Barcelona Spain 08003
    11 Hospital Universitari Vall d'Hebrón Barcelona Spain 08035
    12 Hospital Universitario "Puerta del Mar" Cádiz Spain 11009
    13 Hospital Universitari de Girona Doctor Josep Trueta Girona Spain 17007
    14 Hospital Universitario Virgen de las Nieves Granada Spain 18014
    15 Hospital Universitario Arnau de Vilanova Lleida Spain 25198
    16 Fundación Jiménez Díaz Madrid Spain 28040
    17 Hospital General Universitario "Reina Sofía" Murcia Spain 30003
    18 Hospital Regional Universitario Carlos Haya Málaga Spain 29010
    19 Hospital Universitario de Valme Sevilla Spain 41014
    20 Hospital Clínico Universitario de Valencia Valencia Spain 46010
    21 Hospital Universitario Del Río Hortega Valladolid Spain 47010
    22 Hospital Universitario Miguel Servet Zaragoza Spain 50009

    Sponsors and Collaborators

    • B. Braun Medical SA

    Investigators

    • Study Chair: Abelardo García de Lorenzo, MD, Hospital Universitario La Paz
    • Principal Investigator: Alfonso Bonet Saris, MD_Study Coordinator, Hospital Universitari de Girona Doctor Josep Trueta
    • Study Chair: Teodoro Grau Carmona, MD_Study Coordinator, Hospital Severo Ochoa Leganés (Madrid)

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    B. Braun Medical SA
    ClinicalTrials.gov Identifier:
    NCT00396461
    Other Study ID Numbers:
    • HC-G-H-0510
    • 2005-003542-33
    First Posted:
    Nov 7, 2006
    Last Update Posted:
    Jul 19, 2013
    Last Verified:
    Jul 1, 2013
    Keywords provided by B. Braun Medical SA
    Critical Illness
    Fat Emulsions, Intravenous
    Superinfection
    Parenteral Nutrition
    Additional relevant MeSH terms:
    Cross Infection
    Critical Illness

    Study Results

    No Results Posted as of Jul 19, 2013