While fish-oil lipid emulsions have shown a benefit to the treatment of parenteralnutrition (PN)-associated cholestasis, the dose is limited to 1 g/kg/day. Similarly, inearly PN-associated cholestasis the dose of soy-based lipid is limited to 1 g/kg/day.Often the calories that are lost from this relative decreased dose of lipids can beprovided by adjusting the dextrose content of the PN solution and providing a higherglucose infusion rate. In some cases, this is not tolerated or even with maximizing thisstrategy, growth is inadequate. Inadequate growth is a direct cause of poor outcomesincluding poorer neurological outcome, failure to be able to stop mechanical ventilationand poorer growth of their often already damaged intestine. These outcomes can lead tosevere disability and death. Therefore, infants receiving only 1 g/kg/day of lipids whoare not adequately growing must have a greater intake of lipids to meet their needs forweight, length, and head circumference growth.SMOFlipid (Fresenius Kabi, Bad Homburg, Germany) contains a mixture of 4 different lipidsources: soybean oil providing essential fatty acids, olive oil rich in monounsaturatedfatty acids which are less susceptible to lipid peroxidation than polyunsaturated fattyacids, medium-chain triglycerides showing a faster metabolic clearance than long-chaintriglycerides, and fish oil for the supply of omega-3 fatty acids. It is safe to give inwhat is the usual dose for lipid therapy in neonates of 3 g/kg/day, rather than beinglimited to 1 g/kg/day as we do with cholestatic infants receiving Omegaven or soy lipids.Because this product includes both omega-6 and omega-3 lipids, it provides the benefitsof the omega-3s for the liver and provides more than enough omega-6s to meet essentialfatty acid requirements. Its use in situations in which growth is inadequate in babieswho must be restricted to 1 g/kg/day can be expected to improve their growth and likelymarkedly increase their chances of both a good neurological outcome and survival.Purpose: We want to find out if this new intravenous fat mixture (SMOFlipid) will helppromote good growth while reducing the severity (or seriousness) of liver disease or helpput an end to liver disease in infants.
Therapy with SMOFlipid will be provided at a targeted dose of 3 gm/kg/day (by continuous
infusion). SMOFlipid will be initiated and advanced according to the following
guidelines: Day 1 - provide 1 g/kg; Day 2 - provide 2 g/kg; Day 3 - provide 3 g/kg.
SMOFlipid will be infused intravenously through either a central or peripheral catheter
in conjunction with parenteral nutrition. The same standards of care provided to all
patients receiving parenteral nutrition (PN) solution will be followed.
Essential fatty acid levels will be measured at 4 and 12 weeks after the initiation of
SMOFlipid. This time frame will be used to assess essential fatty acids of both
inpatients and outpatients. These labs are clinically indicated; therefore, we will
record the results of the total fatty acid lipid profile panel from the medical record
into our case report forms.
Patients will remain on SMOFlipid until weaned from PN. In the event that a patient who
has been listed for a liver or liver/intestinal transplant has an organ become available,
the participation in this protocol will not preclude them from receiving the transplant.
SMOFlipid will not be administered post transplant.
If the infant no longer is requiring any PN, then the SMOFlipid will be stopped
regardless of bilirubin. If the bilirubin is less than 2 mg/dL but the child still
requires PN, then the SMOFlipid will be continued up until the infant no longer requires
PN. The reason for stopping SMOFlipid when the infant no longer requires PN is that this
would be the only reason many infants would still need IV access and therefore the risk
of maintaining IV access only for the medication is likely to exceed the benefit of
SMOFlipid at that point.
Babies who receive SMOFlipid are not precluded from receiving Omegaven per that
compassionate use protocol (H-23365) if they meet the inclusion criteria for that
protocol.
Drug: SMOFlipid
Therapy with SMOFlipid will be provided at a targeted dose of 3 gm/kg/day (by continuous
infusion). SMOFlipid will be initiated and advanced according to the following
guidelines: Day 1 - provide 1 g/kg; Day 2 - provide 2 g/kg; Day 3 - provide 3 g/kg.
SMOFlipid will be infused intravenously through either a central or peripheral catheter
in conjunction with parenteral nutrition.
Other Name: SMOF
Inclusion Criteria:
- Greater than 14 days old and less than 1 year of age.
- Greater than 1.5 kg.
- Mild cholestasis, defined as a conjugated bilirubin between 0.5-1.9 mg/dL, or
currently receiving Omegaven (fish oil lipid emulsion) with a conjugated bilirubin
between 0.0-1.9 mg/dL.
- Currently receiving 1 g/kg/day of either Omegaven (H-23365) or soy-based Intralipid
(standard therapy)
- Evidence of growth of weight, head circumference or length below our standards for
post-menstrual age for at least 1 week.
- Be expected to require intravenous nutrition for at least an additional 21 days.
Exclusion Criteria:
- Have a congenitally lethal condition (e.g. Trisomy 13).
- Have clinically severe bleeding or clinical liver failure not able to be managed
with routine measures.
- Have evidence of a viral hepatitis or primary liver disease as the primary etiology
of their cholestasis.
- Have other health problems such that survival is extremely unlikely even if the
infant's cholestasis improves
Baylor College of Medicine / Texas Children's Hospital
Houston, Texas, United States
Investigator: Muralidhar H. Premkumar, MD
Contact: 832-826-7980
premkuma@bcm.edu
Muralidhar H. Premkumar, MD
8328267980
premkuma@bcm.edu
Laura A Gollins, RD
8328263639
laromig@texaschildrens.org
Muralidhar H. Premkumar, MD, Principal Investigator
Baylor College of Medicine