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Can SMOFlipid®, A Composite Parenteral Nutrition Lipid Emulsion, Prevent Progression Of Parenteral Nutrition Associated Liver Disease In Infants?

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ClinicalTrials.gov Identifier: NCT00793195
Recruitment Status : Unknown
Verified November 2011 by The Hospital for Sick Children.
Recruitment status was:  Active, not recruiting
First Posted : November 19, 2008
Last Update Posted : November 3, 2011
Sponsor:
Collaborator:
Fresenius Kabi
Information provided by:
The Hospital for Sick Children

Tracking Information
First Submitted Date  ICMJE November 18, 2008
First Posted Date  ICMJE November 19, 2008
Last Update Posted Date November 3, 2011
Study Start Date  ICMJE January 2009
Actual Primary Completion Date September 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 18, 2008)
Mean serum conjugated bilirubin (umol/L) [ Time Frame: 12 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 18, 2008)
  • Proportion with the development of cholestasis (sustained serum conjugated bilirubin >50 umol/L for greater than 2 weeks in absence of sepsis) [ Time Frame: 12 and 16 weeks ]
  • Proportion with progression of liver disease (sustained serum conjugated bilirubin >100 umol/L in absence of sepsis) [ Time Frame: 12 and 16 weeks ]
  • Degree of enteral tolerance (%) [ Time Frame: 12 and 16 weeks ]
  • Growth parameters [ Time Frame: 12 and 16 weeks ]
  • Biochemical outcomes shall assess mean levels of "hepatic markers" (AST, ALT, ALP, GGT), coagulation parameters (PT, PTT, INR, platelets), serum lipid levels (triglycerides and cholesterol), serum albumin, and Nephelometry (lipid clearance). [ Time Frame: 12 and 16 weeks ]
  • Immunologic outcomes shall include assessment of RBC phospholipids composition, C-reactive Protein (CRP) and serum immunologic marker (IL-1b, IL-2R, IL-6, IL-8, IL-10, TNF-α) assessment [ Time Frame: 12 and 16 weeks ]
  • Feasibility of trial (recruitment, protocol adherence, estimated effect size [ Time Frame: 4, 12 and 16 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Can SMOFlipid®, A Composite Parenteral Nutrition Lipid Emulsion, Prevent Progression Of Parenteral Nutrition Associated Liver Disease In Infants?
Official Title  ICMJE Can SMOFlipid®, A Composite Parenteral Nutrition Lipid Emulsion, Prevent Progression Of Parenteral Nutrition Associated Liver Disease In Infants? A Pilot Double Blind Randomized Controlled Trial
Brief Summary The aim of this study is to determine the feasibility of conducting a trial to examine the efficacy of an ω3FA (Omega-3 fatty acid) containing balanced lipid emulsion in the prevention of progression of PNALD in infants with Intestinal Failure/Short Bowel Syndrome (SBS) and early liver dysfunction.
Detailed Description Parenteral nutrition (PN) associated liver disease (PNALD), remains the primary cause of morbidity and mortality in infants with Short Bowel Syndrome (SBS) and intestinal failure. Although, the etiology is likely multi-factorial, lipids within parenteral nutrition solution have been implicated in its development. The standard lipid used in PN is typically, a soy based lipid (eg: Intralipid® - Fresenius Kabi) that primarily contains omega-6 fatty acids (ω6FAs). Animal and human studies have suggested that addition of omega-3 fatty acids (ω3FAs) to parenteral nutrition may decrease the incidence of hepatic injury, as well as have beneficial immunologic effects. SMOFlipid® (Fresenius Kabi) is a composite lipid emulsion, which contains polyunsaturated ω3 and ω6FAs, monounsaturated FAs, as well as medium chain FAs as integral constituents. All components (Soy-bean oil, medium chain triglycerides, olive oil, fish oil) have been used in humans, and the drug is approved for use in children in Europe. Based on its composition, we believe that this lipid preparation has the potential to prevent progression of liver disease in infants with SBS who are demonstrating evidence of liver dysfunction.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Short Bowel Syndrome
  • Intestinal Failure
  • Gastrointestinal Motility Disorder
  • Mucosal Enteropathy
Intervention  ICMJE
  • Drug: Intralipid 20%
    Dosing will be formulated according to a Nomogram for Parenteral Nutrition (PN) composition, which takes into account the percentage of the subject's caloric intake consumed parenterally. PN solution will be infused continuously over 12-24 hours by infusion pump, and the duration each day will depend on the enteral tolerance of the child. PN shall not be discontinued, unless the patient is taking 95% of calories enterally with good growth as evidence by appropriate weight gain. Subjects will receive the trial lipid for a total duration of 12 weeks or if they develop a serum conjugated bilirubin (sustained for 7 days) of 100 umol/l (6mg/dl) or full enteral tolerance prior to this end-point. Once the trial lipid is discontinued, in the event that PN is continued, subjects will return to the standard lipid preparation. A final follow-up data-point will be collected 4 weeks after the trial lipid is stopped.
  • Drug: SMOFlipid 20%
    Dosing will be formulated according to a Nomogram for Parenteral Nutrition (PN) composition, which takes into account the percentage of the subject's caloric intake consumed parenterally. PN solution will be infused continuously over 12-24 hours by infusion pump, and the duration each day will depend on the enteral tolerance of the child. PN shall not be discontinued, unless the patient is taking 95% of calories enterally with good growth as evidence by appropriate weight gain. Subjects will receive the trial lipid for a total duration of 12 weeks or if they develop a serum conjugated bilirubin (sustained for 7 days) of 100 umol/l (6mg/dl) or full enteral tolerance prior to this end-point. Once the trial lipid is discontinued, in the event that PN is continued, subjects will return to the standard lipid preparation. A final follow-up data-point will be collected 4 weeks after the trial lipid is stopped.
Study Arms  ICMJE
  • Active Comparator: 1) Intralipid
    Fat Emulsions for Intravenous Nutrition
    Intervention: Drug: Intralipid 20%
  • Experimental: 2) SMOFlipid
    Fat Emulsions for Intravenous Nutrition
    Intervention: Drug: SMOFlipid 20%
Publications * Diamond IR, Grant RC, Pencharz PB, de Silva N, Feldman BM, Fitzgerald P, Sigalet D, Dicken B, Turner J, Marchand V, Ling SC, Moore AM, Avitzur Y, Wales PW. Preventing the Progression of Intestinal Failure-Associated Liver Disease in Infants Using a Composite Lipid Emulsion: A Pilot Randomized Controlled Trial of SMOFlipid. JPEN J Parenter Enteral Nutr. 2017 Jul;41(5):866-877. doi: 10.1177/0148607115626921. Epub 2016 Feb 2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: November 18, 2008)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2012
Actual Primary Completion Date September 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. ≤ 24 months of age at enrollment
  2. Evidence of early hepatic dysfunction

    • Serum conjugated bilirubin ≥ 17 umol/L on 2 consecutive readings 7 days apart

      • No evidence of sepsis

        • Normal Temperature (T between 35.5C and 38.0C)
        • Normal leukocyte count
        • Normal platelet count
        • No systemic septic symptoms
      • No prior administration of Omegaven
  3. ≥ 40% of total calories administered by PN
  4. Meet one of the following diagnostic categories

    • Short Bowel Syndrome

      • Abdominal surgical procedure including gastroschisis closure by any means and percutaneous drainage procedures within the past 6 months and has been receiving PN since surgery
    • Intestinal Failure

      • One of the following diagnoses for which the child is dependent on PN

        • Gastrointestinal Motility Disorder
        • Mucosal Enteropathy
  5. Expectation of the treating physician that the patient will require PN for at least 3 weeks following enrollment.
  6. Parents willing to participate including randomization

Exclusion Criteria:

  1. Sepsis or Hemodynamic Instability of any cause.
  2. Coagulopathy (Platelets ≤ 150 000, or INR ≥ 1.4)
  3. Hypersensitivity to fish-, egg- or soy protein or to any of the active substances or excipients
  4. Current enrollment in another clinical trial involving a surgical or pharmacologic intervention
  5. Serum conjugated bilirubin > 50 umol/L
  6. Hyperlipidaemia (any of)

    • LDL ≥ 4 mmol/L
    • HDL ≥ 2 mmol/L
    • Total cholesterol ≥ 5 mmol/L
    • Triglycerides ≥ 1.5 mmol/L
  7. Treatment with intravenous N-Acetylcysteine or Ursodeoxycholic acid
  8. Renal insufficiency

    • Creatinine ≥ 80 umol/L
  9. Disorders of Fluid Balance (any of)

    • Serum Sodium < 130 mmol/L
    • Serum Sodium > 145 mmol/L
  10. Unstable conditions

    • Acute pulmonary edema
    • Decompensated cardiac insufficiency
    • Severe post-traumatic conditions
    • Uncompensated diabetes mellitus
    • Acute myocardial infarction
    • Stroke within 3 months
    • Thromboembolic event within 3 months
    • Metabolic acidosis

      • Serum Bicarbonate < 17 mmol/L
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 24 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00793195
Other Study ID Numbers  ICMJE 1000012566
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr. Paul Wales, The Hospital for Sick Children
Study Sponsor  ICMJE The Hospital for Sick Children
Collaborators  ICMJE Fresenius Kabi
Investigators  ICMJE
Principal Investigator: Paul Wales The Hospital for Sick Children
PRS Account The Hospital for Sick Children
Verification Date November 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP