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

The Hospital for Sick Children

Status and phase: Unknown; Phase 2

Conditions: Intestinal Failure; Short Bowel Syndrome; Mucosal Enteropathy; Gastrointestinal Motility Disorder

Treatments: Drug: SMOFlipid 20%; Drug: Intralipid 20%

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00793195

1000012566

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 estimated patients

Sex: All

Ages: Under 24 months old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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24 participants in 2 patient groups

1) Intralipid

Active Comparator group

Description:

Fat Emulsions for Intravenous Nutrition

Treatment:

Drug: Intralipid 20%

2) SMOFlipid

Experimental group

Description:

Fat Emulsions for Intravenous Nutrition

Treatment:

Drug: SMOFlipid 20%