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

July 18, 2013 updated by: B. Braun Medical SA

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.

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

212

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Alicante, Spain, 03010
        • Hospital General Universitario de Alicante
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Barcelona, Spain, 08003
        • Hospital del Mar (Institut Municipal d'Assistència Sanitària, IMAS)
      • Cádiz, Spain, 11009
        • Hospital Universitario "Puerta del Mar"
      • Girona, Spain, 17007
        • Hospital Universitari de Girona Doctor Josep Trueta
      • Granada, Spain, 18014
        • Hospital Universitario Virgen de las Nieves
      • Lleida, Spain, 25198
        • Hospital Universitario Arnau de Vilanova
      • Madrid, Spain, 28040
        • Fundacion Jimenez Diaz
      • Murcia, Spain, 30003
        • Hospital General Universitario "Reina Sofía"
      • Málaga, Spain, 29010
        • Hospital Regional Universitario Carlos Haya
      • Sevilla, Spain, 41014
        • Hospital Universitario de Valme
      • Valencia, Spain, 46010
        • Hospital Clínico Universitario de Valencia
      • Valladolid, Spain, 47010
        • Hospital Universitario del Río Hortega
      • Zaragoza, Spain, 50009
        • Hospital Universitario Miguel Servet
    • Baleares
      • Palma de Mallorca, Baleares, Spain, 07014
        • Hospital Son Dureta
    • Barcelona
      • Hospitalet de Llobregat, Barcelona, Spain, 08097
        • Hospital Universitario de Bellvitge (H.U.B.)
    • Bizcaya
      • Barakaldo, Bizcaya, Spain, 48903
        • Hospital de Cruces
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Hospital Universitario Marques de Valdecilla
    • Gran Canaria
      • Las Palmas de Gran Canaria, Gran Canaria, Spain, 35010
        • Hospital Universitario de Gran Canaria Dr. Negrin
      • Las Palmas de Gran Canaria, Gran Canaria, Spain, 35016
        • Complejo Hospitalario Materno Insular de Gran Canaria
    • Madrid
      • Leganés, Madrid, Spain, 28911
        • Hospital Severo Ochoa
    • Murcia
      • El Palmar, Murcia, Spain, 30120
        • Hospital Universitario "Virgen de la Arrixaca"

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
Time Frame: 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.
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.
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.
Time Frame: 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.
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

Outcome Measure
Time Frame
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.
Time Frame: At the end of the study and 6 months after discharge from ICU.
At the end of the study and 6 months after discharge from ICU.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2006

Primary Completion (ACTUAL)

September 1, 2010

Study Completion (ACTUAL)

February 1, 2011

Study Registration Dates

First Submitted

November 3, 2006

First Submitted That Met QC Criteria

November 6, 2006

First Posted (ESTIMATE)

November 7, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

July 19, 2013

Last Update Submitted That Met QC Criteria

July 18, 2013

Last Verified

July 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HC-G-H-0510
  • 2005-003542-33 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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