Fat Tolerance From Lipid Emulsion Infusion Packaged in Glass or Plastic
| Status: | Terminated |
|---|---|
| Conditions: | High Cholesterol, Metabolic |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Pharmacology / Toxicology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 3/15/2017 |
| Start Date: | January 2006 |
| End Date: | April 2007 |
Prospective, Randomized Study of Fat Tolerance From Lipid Emulsion Infusion Packaged in Glass or Plastic Containers.
This will be a prospective, randomized trial to determine if differences exist in the
tolerance of lipid injectable emulsions in the neonatal intensive care unit (NICU). Lipid
injectable emulsions are an essential nutrient for neonatal growth and development.
Traditionally, lipid injectable emulsions have been commercially available in sterile glass
bottles, but in April of 2004, a new container was introduced as a sterile plastic bag. In
January, 2005, NICU personnel observed what appeared to be a higher than usual incidence of
hypertriglyceridemia. Upon further laboratory investigation of the lipid injectable
emulsions stored in glass bottles versus those in plastic, significant differences were
noted in the population of large-diameter fat globules by globule size analysis, reflective
of a less stable emulsion in plastic. The United States Pharmacopeia (USP) which sets the
standards for drug purity and safety in the U.S., and whose drug monographs are enforceable
by the FDA, has proposed to limit this large diameter fat globule population to a
volume-weighted percent fat greater than five micrometers or PFAT5 to be less than 0.05% of
the total lipid concentration. (At the present time, the USP monograph is not officially
recognized, but is on track for adoption in 2006.) Our preliminary analyses of four lots of
20% lipid injectable emulsion packaged in glass to have a PFAT5 of 0.003±0.0008%, compared
to an approximate 55-fold increase in the large-diameter fat globule population or
0.166±0.016% for an equal number of products packaged in plastic. We hypothesize this
difference may explain the recent clinical observations. We will compare the incidence of
hypertriglyceridemia in neonates between lipids packaged in glass versus those in plastic.
The study will attempt to discern whether the differences in packaging influence the
stability and subsequent tolerance of lipid injectable emulsions.
tolerance of lipid injectable emulsions in the neonatal intensive care unit (NICU). Lipid
injectable emulsions are an essential nutrient for neonatal growth and development.
Traditionally, lipid injectable emulsions have been commercially available in sterile glass
bottles, but in April of 2004, a new container was introduced as a sterile plastic bag. In
January, 2005, NICU personnel observed what appeared to be a higher than usual incidence of
hypertriglyceridemia. Upon further laboratory investigation of the lipid injectable
emulsions stored in glass bottles versus those in plastic, significant differences were
noted in the population of large-diameter fat globules by globule size analysis, reflective
of a less stable emulsion in plastic. The United States Pharmacopeia (USP) which sets the
standards for drug purity and safety in the U.S., and whose drug monographs are enforceable
by the FDA, has proposed to limit this large diameter fat globule population to a
volume-weighted percent fat greater than five micrometers or PFAT5 to be less than 0.05% of
the total lipid concentration. (At the present time, the USP monograph is not officially
recognized, but is on track for adoption in 2006.) Our preliminary analyses of four lots of
20% lipid injectable emulsion packaged in glass to have a PFAT5 of 0.003±0.0008%, compared
to an approximate 55-fold increase in the large-diameter fat globule population or
0.166±0.016% for an equal number of products packaged in plastic. We hypothesize this
difference may explain the recent clinical observations. We will compare the incidence of
hypertriglyceridemia in neonates between lipids packaged in glass versus those in plastic.
The study will attempt to discern whether the differences in packaging influence the
stability and subsequent tolerance of lipid injectable emulsions.
The study is a single-center (BIDMC), prospective, single-blinded, randomized controlled
study involving neonatal ICU patients who will receive lipid injectable emulsion infusions
as part of their normal clinical care. The dosing protocol for all neonates is weight- and
age-based, as shown below:
Birth Weight (< 1000 g)
Age(Day of Life,DOL)- Lipid Dose g/kg/day:
DOL1- 0; DOL2- 1; DOL3- 1.5; DOL4- 2; DOL5- 2.5; DOL6+-3
Birth Weight (>1000 g)
Age-Lipid Dose g/kg/day:
DOL1- 0; DOL2- 1; DOL3- 2; DOL4- 3; DOL5- 3; DOL6+-3
Serum triglycerides is the primary outcome indicator of tolerance to the initiation and
advancement of lipid injectable emulsion. Blood samples will be drawn before initiation of
lipids at either DOL-0 or DOL-1, and then at DOL-4 and DOL-7.
The procedures for initiating lipid emulsions in neonates will follow the usual protocol as
per NICU guidelines. On DOL-2, an order for 20% soybean oil lipid emulsion will be written
by a physician or designated licensed assistant as per protocol. The Pharmacy Department
will receive the order, and compound and dispense it in an appropriately sized syringe.
Patients will receive lipids taken from either glass bottles or plastic bags according to a
pre-assigned randomization scheme.
All lipid injectable emulsion lots in glass and plastic will be recorded as used in the
study. In addition, all lots will be analyzed with respect to the globule size distributions
in the Nutrition/Infection Laboratory.
Sample Size Justification:
Approximately 82 randomized patients are required for analysis of the differences between
lipid injectable emulsion formulations.
The sample size was generated from the data obtained from the retrospective analysis
described above in B2. A two-sided test based on a normal distribution, a nominal
significance level of 0.05, and a statistical power of 0.80 were assumed. Based on these
assumptions, the power calculation reveals an equal sample size for both groups is
calculated to be 41. Hence, the total sample size of 82 patients is required to detect
statistically significant differences in the incidence of hypertriglyceridemia between
infusion groups.
Data Analysis:
We will be comparing lipid tolerance in critically ill neonates receiving pharmacy-prepared
syringes of 20% soybean oil-based lipid injectable emulsion taken from commercially
available, FDA-approved products that use either a glass or plastic packaging container. The
primary outcome variable in assessing lipid tolerance will be serum triglycerides. A two-way
analysis of variance (ANOVA) will be employed to assess the differences between lipid
injectable emulsion products. The two independent variables are 1) Lipid Container (or
Treatment) and, 2) Time (over 7 days); while the dependent variable will be serum
triglycerides. If significant differences are detected by ANOVA, then individual differences
will be further evaluated using Bonferroni tests for pair wise comparisons. All data will be
expressed as the mean ± SD with statistical significance set at a p-value of <0.05. Analysis
will be done at BIDMC under the supervision of the study PI. Although not expected to play a
significant role, drop-out and missing data will be adjusted accordingly.
All patients who present to the neonatal intensive care unit at BIDMC who require
intravenous nutritional support and provide informed consent will be included in the study.
The decision to initiate intravenous nutritional support will be made by clinical personnel,
and the dosing protocol for lipid injectable emulsion will follow institutional procedures
as shown above in B3 (Description of Study Protocol) (section1-a). Patients will be
randomized to receive one of two study parenteral lipid emulsions. As hydrocortisone therapy
is rarely used in the treatment of refractory hypotension in neonates, and has been shown to
induce hypertriglyceridemia in very low birth weight infants (younger than 29 weeks'
gestational age at birth), such patients will be excluded from study. Due to randomization,
patients enrolled in either group are expected to be similarly distributed with respect to
gestational age, gender and race.
Potential study subjects will be identified by neonatal intensive care unit physicians at
BIDMC who have determined intravenous nutrition support is clinically indicated. Parent(s)
or guardian(s) of the NICU patient will review and sign a written informed consent form. The
form will be obtained by NICU physicians or one of the co-investigators listed above.
Prospective parents or guardians of the patient will be presented, in lay terms, the two
options for providing intravenous lipid emulsions. The purpose of the study and current data
regarding the standard of care will be presented to parents or guardians of the patient, and
that assignment to either group (glass vs. plastic) will be random or determined by chance.
Parents or guardians will be informed that participation is completely voluntary and that
all patient data will be kept confidential. All aspects of this study will take place in the
neonatal intensive care unit.
study involving neonatal ICU patients who will receive lipid injectable emulsion infusions
as part of their normal clinical care. The dosing protocol for all neonates is weight- and
age-based, as shown below:
Birth Weight (< 1000 g)
Age(Day of Life,DOL)- Lipid Dose g/kg/day:
DOL1- 0; DOL2- 1; DOL3- 1.5; DOL4- 2; DOL5- 2.5; DOL6+-3
Birth Weight (>1000 g)
Age-Lipid Dose g/kg/day:
DOL1- 0; DOL2- 1; DOL3- 2; DOL4- 3; DOL5- 3; DOL6+-3
Serum triglycerides is the primary outcome indicator of tolerance to the initiation and
advancement of lipid injectable emulsion. Blood samples will be drawn before initiation of
lipids at either DOL-0 or DOL-1, and then at DOL-4 and DOL-7.
The procedures for initiating lipid emulsions in neonates will follow the usual protocol as
per NICU guidelines. On DOL-2, an order for 20% soybean oil lipid emulsion will be written
by a physician or designated licensed assistant as per protocol. The Pharmacy Department
will receive the order, and compound and dispense it in an appropriately sized syringe.
Patients will receive lipids taken from either glass bottles or plastic bags according to a
pre-assigned randomization scheme.
All lipid injectable emulsion lots in glass and plastic will be recorded as used in the
study. In addition, all lots will be analyzed with respect to the globule size distributions
in the Nutrition/Infection Laboratory.
Sample Size Justification:
Approximately 82 randomized patients are required for analysis of the differences between
lipid injectable emulsion formulations.
The sample size was generated from the data obtained from the retrospective analysis
described above in B2. A two-sided test based on a normal distribution, a nominal
significance level of 0.05, and a statistical power of 0.80 were assumed. Based on these
assumptions, the power calculation reveals an equal sample size for both groups is
calculated to be 41. Hence, the total sample size of 82 patients is required to detect
statistically significant differences in the incidence of hypertriglyceridemia between
infusion groups.
Data Analysis:
We will be comparing lipid tolerance in critically ill neonates receiving pharmacy-prepared
syringes of 20% soybean oil-based lipid injectable emulsion taken from commercially
available, FDA-approved products that use either a glass or plastic packaging container. The
primary outcome variable in assessing lipid tolerance will be serum triglycerides. A two-way
analysis of variance (ANOVA) will be employed to assess the differences between lipid
injectable emulsion products. The two independent variables are 1) Lipid Container (or
Treatment) and, 2) Time (over 7 days); while the dependent variable will be serum
triglycerides. If significant differences are detected by ANOVA, then individual differences
will be further evaluated using Bonferroni tests for pair wise comparisons. All data will be
expressed as the mean ± SD with statistical significance set at a p-value of <0.05. Analysis
will be done at BIDMC under the supervision of the study PI. Although not expected to play a
significant role, drop-out and missing data will be adjusted accordingly.
All patients who present to the neonatal intensive care unit at BIDMC who require
intravenous nutritional support and provide informed consent will be included in the study.
The decision to initiate intravenous nutritional support will be made by clinical personnel,
and the dosing protocol for lipid injectable emulsion will follow institutional procedures
as shown above in B3 (Description of Study Protocol) (section1-a). Patients will be
randomized to receive one of two study parenteral lipid emulsions. As hydrocortisone therapy
is rarely used in the treatment of refractory hypotension in neonates, and has been shown to
induce hypertriglyceridemia in very low birth weight infants (younger than 29 weeks'
gestational age at birth), such patients will be excluded from study. Due to randomization,
patients enrolled in either group are expected to be similarly distributed with respect to
gestational age, gender and race.
Potential study subjects will be identified by neonatal intensive care unit physicians at
BIDMC who have determined intravenous nutrition support is clinically indicated. Parent(s)
or guardian(s) of the NICU patient will review and sign a written informed consent form. The
form will be obtained by NICU physicians or one of the co-investigators listed above.
Prospective parents or guardians of the patient will be presented, in lay terms, the two
options for providing intravenous lipid emulsions. The purpose of the study and current data
regarding the standard of care will be presented to parents or guardians of the patient, and
that assignment to either group (glass vs. plastic) will be random or determined by chance.
Parents or guardians will be informed that participation is completely voluntary and that
all patient data will be kept confidential. All aspects of this study will take place in the
neonatal intensive care unit.
Inclusion Criteria:
- All patients who present to the neonatal intensive care unit at BIDMC who require
intravenous nutritional support
Exclusion Criteria:
- Any patients receiving intravenous steroids
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