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

Purpose

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.

Condition	Intervention	Phase
Short Bowel Syndrome Intestinal Failure Gastrointestinal Motility Disorder Mucosal Enteropathy	Drug: Intralipid 20% Drug: SMOFlipid 20%	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Liver Diseases

Drug Information available for: Liposyn II Liposyn III Parenteral Nutrition, Total

Genetic and Rare Diseases Information Center resources: Short Bowel Syndrome

U.S. FDA Resources

Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:

Mean serum conjugated bilirubin (umol/L) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ]


Estimated Enrollment:	24
Study Start Date:	January 2009
Estimated Study Completion Date:	January 2012
Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1) Intralipid Fat Emulsions for Intravenous Nutrition	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.
Experimental: 2) SMOFlipid Fat Emulsions for Intravenous Nutrition	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.

Arms

Assigned Interventions

Active Comparator: 1) Intralipid

Fat Emulsions for Intravenous Nutrition

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.

Experimental: 2) SMOFlipid

Fat Emulsions for Intravenous Nutrition

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.

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.

Eligibility


Ages Eligible for Study:	up to 24 Months
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

≤ 24 months of age at enrollment
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
≥ 40% of total calories administered by PN
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
Expectation of the treating physician that the patient will require PN for at least 3 weeks following enrollment.
Parents willing to participate including randomization

Exclusion Criteria:

Sepsis or Hemodynamic Instability of any cause.
Coagulopathy (Platelets ≤ 150 000, or INR ≥ 1.4)
Hypersensitivity to fish-, egg- or soy protein or to any of the active substances or excipients
Current enrollment in another clinical trial involving a surgical or pharmacologic intervention
Serum conjugated bilirubin > 50 umol/L
Hyperlipidaemia (any of)
- LDL ≥ 4 mmol/L
- HDL ≥ 2 mmol/L
- Total cholesterol ≥ 5 mmol/L
- Triglycerides ≥ 1.5 mmol/L
Treatment with intravenous N-Acetylcysteine or Ursodeoxycholic acid
Renal insufficiency
- Creatinine ≥ 80 umol/L
Disorders of Fluid Balance (any of)
- Serum Sodium < 130 mmol/L
- Serum Sodium > 145 mmol/L
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

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: NCT00793195

Locations


Canada, Alberta
Alberta Children's Hospital
Calgary, Alberta, Canada
Foothills Medical Center
Calgary, Alberta, Canada
Stollery Children's Hospital
Edmonton, Alberta, Canada
Canada, Ontario
Hamilton Health Sciences
Hamilton, Ontario, Canada, L8N 3Z5
The Hospital for Sick Children
Toronto, Ontario, Canada

Sponsors and Collaborators

The Hospital for Sick Children

Fresenius Kabi

Investigators


Principal Investigator:	Paul Wales	The Hospital for Sick Children

More Information

No publications provided


Responsible Party:	Dr. Paul Wales, The Hospital for Sick Children
ClinicalTrials.gov Identifier:	NCT00793195 History of Changes
Other Study ID Numbers:	1000012566
Study First Received:	November 18, 2008
Last Updated:	November 2, 2011
Health Authority:	Canada: Health Canada

Keywords provided by The Hospital for Sick Children:


Neonates Short Bowel Syndrome Intestinal Failure Liver Failure	Parenteral Nutrition Intralipid SMOF

Additional relevant MeSH terms:


Short Bowel Syndrome Digestive System Diseases Gastrointestinal Diseases Intestinal Diseases	Malabsorption Syndromes Pathologic Processes Postoperative Complications

ClinicalTrials.gov processed this record on February 27, 2015