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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
B. Braun Medical SA
ClinicalTrials.gov Identifier:
NCT00396461
First received: November 3, 2006
Last updated: July 18, 2013
Last verified: July 2013
  Purpose

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 Intervention Phase
Critical Illness
Drug: MCT/LCT (1:1)
Drug: MCT/LCT/omega-3 (5:4:1)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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.

Further study details as provided by B. Braun Medical SA:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]
  • 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. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 212
Study Start Date: November 2006
Study Completion Date: February 2011
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: LIPOPLUS

  Hide Detailed Description

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00396461

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

Additional Information:
Publications:
Carpentier YA, Van Gossum A, Dubois D, Deckeibaum R. Lipid Metabolism in Parenteral Nutrition. In: Wilmore DW, Carpentier YA (Eds). Metabolic Support of the Critically III Patient. Berlin, Springer-Veriag 1993, pp 35-74
Driscoll DF, Adolph M, Bistrian BR. Lipid emulsions in parenteral nutrition. In: Rombeau JL, Rolandelli R, eds. Parenteral nutrition. Philadelphia: W. B. Saunders Company; 2000:35-39.
Kumar SG, Das UN, Kumar KV, Madhavi N, Das NP, Tan BKH. Effect of n-6 and n-3 fatty acids on the proliferation of human lymphocyes and their secretion of TN F-alpha and IL-2 in vitro. Nutr Res 1992; 12: 815-823.
Grimminger F, Seeger W, Mayer K. Use of n-3 fatty acid-containing lipid emulsions in the intensive care unit environment: the clinician's view. Clinical Nutrition 2002, 21, Supplement 2: 23-29.
Wichmann MW, Morlion B, Czarnetzki H-D, Thul P, Jauch K-W. Reduction of length of postoperative stay by fish oil containing lipid emulsion - data from a multicenter trial. Clinical Nutrition 2004, 23: 1471

Responsible Party: B. Braun Medical SA
ClinicalTrials.gov Identifier: NCT00396461     History of Changes
Other Study ID Numbers: HC-G-H-0510, 2005-003542-33
Study First Received: November 3, 2006
Last Updated: July 18, 2013
Health Authority: Spain: Spanish Agency of Medicines
Spain: Ministry of Health and Consumption

Keywords provided by B. Braun Medical SA:
Critical Illness
Fat Emulsions, Intravenous
Superinfection
Parenteral Nutrition

Additional relevant MeSH terms:
Critical Illness
Cross Infection
Disease Attributes
Infection
Pathologic Processes

ClinicalTrials.gov processed this record on October 23, 2014