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

NCT ID: NCT00793195

Last Updated: 2011-11-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2012-01-31

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

1) Intralipid

Fat Emulsions for Intravenous Nutrition

Group Type: ACTIVE_COMPARATOR

Intralipid 20%

Intervention Type: DRUG

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.

2) SMOFlipid

Fat Emulsions for Intravenous Nutrition

Group Type: EXPERIMENTAL

SMOFlipid 20%

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Maximum Eligible Age: 24 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fresenius Kabi

INDUSTRY

Sponsor Role: collaborator

The Hospital for Sick Children

OTHER

Sponsor Role: lead

Responsible Party

The Hospital for Sick Children

Principal Investigators

Paul Wales

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children

Locations

Alberta Children's Hospital

Calgary, Alberta, Canada

Foothills Medical Center

Calgary, Alberta, Canada

Stollery Children's Hospital

Edmonton, Alberta, Canada

Hamilton Health Sciences

Hamilton, Ontario, Canada

The Hospital for Sick Children

Toronto, Ontario, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 26838529 (View on PubMed)

Other Identifiers

1000012566

Identifier Type: -

Identifier Source: org_study_id