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

NCT00793195 | Unknown Phase 2 DMC

• 1 other identifier: 1000012566
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Mean serum conjugated bilirubin (umol/L)

  12 weeks

Secondary Outcomes (7)

• Proportion with the development of cholestasis (sustained serum conjugated bilirubin >50 umol/L for greater than 2 weeks in absence of sepsis)

  12 and 16 weeks

• Proportion with progression of liver disease (sustained serum conjugated bilirubin >100 umol/L in absence of sepsis)

  12 and 16 weeks

• Degree of enteral tolerance (%)

  12 and 16 weeks

• Growth parameters

  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).

  12 and 16 weeks

Study Arms (2)

1) Intralipid

ACTIVE COMPARATOR

Fat Emulsions for Intravenous Nutrition

Drug: Intralipid 20%

2) SMOFlipid

EXPERIMENTAL

Fat Emulsions for Intravenous Nutrition

Drug: SMOFlipid 20%

Interventions

Intralipid 20% 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.

1) Intralipid

SMOFlipid 20% 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

Eligibility Criteria

• Age: Up to 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• ≤ 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• Fresenius Kabi: collaborator

Study Sites (5)

Alberta Children's Hospital

Calgary, Alberta, Canada

Location

Foothills Medical Center

Calgary, Alberta, Canada

Location

Stollery Children's Hospital

Edmonton, Alberta, Canada

Location

Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, Canada

Location

Related Publications (1)

• 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.

  PMID: 26838529 DERIVED

MeSH Terms

Conditions

Short Bowel Syndrome; Intestinal Failure; Liver Failure; Hyperphagia

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hepatic Insufficiency; Liver Diseases; Signs and Symptoms, Digestive; Signs and Symptoms

Study Officials

• Paul Wales

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 18, 2008
• First Posted: November 19, 2008
• Study Start: January 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: January 1, 2012
• Last Updated: November 3, 2011

Record last verified: 2011-11

Locations

CA (5)