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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2011 by The Hospital for Sick Children.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Fresenius Kabi
Information provided by:
The Hospital for Sick Children
ClinicalTrials.gov Identifier:
NCT00793195
First received: November 18, 2008
Last updated: November 2, 2011
Last verified: November 2011

November 18, 2008
November 2, 2011
January 2009
September 2011   (final data collection date for primary outcome measure)
Mean serum conjugated bilirubin (umol/L) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00793195 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: Yes ]
  • Proportion with progression of liver disease (sustained serum conjugated bilirubin >100 umol/L in absence of sepsis) [ Time Frame: 12 and 16 weeks ] [ Designated as safety issue: Yes ]
  • Degree of enteral tolerance (%) [ Time Frame: 12 and 16 weeks ] [ Designated as safety issue: No ]
  • Growth parameters [ Time Frame: 12 and 16 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Feasibility of trial (recruitment, protocol adherence, estimated effect size [ Time Frame: 4, 12 and 16 weeks ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Can SMOFlipid®, A Composite Parenteral Nutrition Lipid Emulsion, Prevent Progression Of Parenteral Nutrition Associated Liver Disease In Infants?
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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
  • Short Bowel Syndrome
  • Intestinal Failure
  • Gastrointestinal Motility Disorder
  • Mucosal Enteropathy
  • 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.
  • 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%
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
24
January 2012
September 2011   (final data collection date for primary outcome measure)

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
Both
up to 24 Months
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00793195
1000012566
Yes
Dr. Paul Wales, The Hospital for Sick Children
The Hospital for Sick Children
Fresenius Kabi
Principal Investigator: Paul Wales The Hospital for Sick Children
The Hospital for Sick Children
November 2011

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