Cholestasis
Conditions
Keywords
preterm, parenteral nutrition, cholestasis, fish oil
Brief summary
The purpose of this study is to compare the effects of a multicomponent lipid emulsion containing 30% soybean oil, 30% medium-chain triglycerides, 25% olive oil, and 15% fish oil with a conventional pure soybean oil lipid emulsion on the incidence of neonatal cholestasis, infant growth, infant morbidity and the biochemical assessment of liver enzymes.
Detailed description
Intravenous lipid emulsions are the major sources of non-protein energy and provision of required essential fatty acids. The reference lipid emulsion, widely used for many years, is prepared from soybean oil, which is rich in omega 6 polyunsaturated fatty acids and phytosterols that contribute to hepatotoxicity and their metabolites result in pro-inflammatory eicosanoid production. Existing evidence strongly supports a pathogenetic role of inflammation and oxidative stress on parenteral nutrition associated liver disease. Subsequent development of lipid emulsions has focused on reducing the amount of soybean oil and replacing it with other oils.Moreover the omega 3 fatty acids from fish oil are metabolized to anti-inflammatory eicosanoids which can prevent inflammatory responses. A novel multicomponent lipid emulsion may prevent liver injury, improve growth and decrease morbidity in preterm infants.
Interventions
DRUGmulticomponent lipid emulsion
Lipids were first administered at a dose of 1gm/kg/day within 24 hours after birth for both groups; lipid dosage was increased by an increment of 0.5 gm/kg/day until the maximal dose of 3.5 gm/kg/day was reached.
DRUGpure soybean oil lipid emulsion
Lipids were first administered at a dose of 1gm/kg/day within 24 hours after birth for both groups; lipid dosage was increased by an increment of 0.5 gm/kg/day until the maximal dose of 3.5 gm/kg/day was reached.
Sponsors
Thammasat University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
24 Weeks to 30 Weeks
Healthy volunteers
No
Inclusion criteria
* Inborn infants with a gestational age of less than 30 weeks * Who required parenteral nutrition for at least 7 days
Exclusion criteria
* Evidence of congenital infection * Perinatal asphyxia * Congenital anomalies * Severe IVH * Thrombocytopenia * Shock or circulation failure * Renal or hepatic disorders.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Neonatal Cholestasis | 3 months | direct bilirubin level of more than 2 mg/dL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Extrauterine Growth Restriction (EUGR) | up to 24 weeks | weight that is less than the tenth percentile for corrected gestational age by the time of discharge |
| Weight Gain | up to 24 weeks | in-hospital weight gain at birth until discharge (gram/day) |
| Height Gain | up to 24 weeks | in-hospital height gain at birth until discharge (cm/week) |
| Neonatal Morbidities | 4 months | retinopathy of prematurity, bronchopulmonary dysplasia |
| Assessment of Gamma Glutamyltranspeptidase (GGT) | 3 month | blood samples were obtained before enrollment, week 1, 2 and 3 (U/L) after parenteral nutrition administration |
| Assessment of Alanine Aminotransferase (ALT) | 3 month | blood samples were obtained before enrollment, week 1, 2 and 3 (U/L) after parenteral nutrition administration |
| Assessment of Aspartate Aminotransferase (AST) | 3 month | blood samples were obtained before enrollment, week 1, 2 and 3 (U/L) after parenteral nutrition administration |
| Head Circumference Gain | up to 24 weeks | in-hospital head circumference gain at birth until discharge (cm/week) |
Participant flow
Recruitment details
This study enrolled preterm infants who required parenteral nutrition for at least 7 days from 2 academic medical centers in Bangkok. The last patient completed in December 2015
Participants by arm
| Arm | Count |
|---|---|
| Study Group multicomponent lipid emulsion composed of 30% soybean oil, 30% MCTs, 25% olive oil and 15% fish oil (SMOF lipid) was administered at a dose of 1gm/kg/day within 24 hours after birth; lipid dosage was increased by an increment of 0.5 gm/kg/day until the maximal dose of 3.5 gm/kg/day was reached.The macronutrients and micronutrients were provided using the same products in both groups.
multicomponent lipid emulsion: Lipids were first administered at a dose of 1gm/kg/day within 24 hours after birth for both groups; lipid dosage was increased by an increment of 0.5 gm/kg/day until the maximal dose of 3.5 gm/kg/day was reached. | 22 |
| Control Group pure soybean oil lipid emulsion(intralipid) was administered at a dose of 1gm/kg/day within 24 hours after birth; lipid dosage was increased by an increment of 0.5gm/kg/day until the maximal dose of 3.5gm/kg/day was reached.The macronutrients and micronutrients were provided using the same products in both groups.
pure soybean oil lipid emulsion: Lipids were first administered at a dose of 1gm/kg/day within 24 hours after birth for both groups; lipid dosage was increased by an increment of 0.5 gm/kg/day until the maximal dose of 3.5 gm/kg/day was reached. | 22 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 4 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Study Group | Control Group | Total |
|---|---|---|---|
| Age, Continuous | 27.6 weeks STANDARD_DEVIATION 2.2 | 28.4 weeks STANDARD_DEVIATION 1.2 | 28.0 weeks STANDARD_DEVIATION 1.8 |
| Region of Enrollment Thailand | 22 participants | 22 participants | 44 participants |
| Sex: Female, Male Female | 14 Participants | 14 Participants | 28 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 22 | 4 / 22 |
| other Total, other adverse events | 0 / 22 | 0 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 |
Outcome results
Primary
Incidence of Neonatal Cholestasis
direct bilirubin level of more than 2 mg/dL
Time frame: 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study Group | Incidence of Neonatal Cholestasis | 1 Participants |
| Control Group | Incidence of Neonatal Cholestasis | 2 Participants |
Secondary
Assessment of Alanine Aminotransferase (ALT)
blood samples were obtained before enrollment, week 1, 2 and 3 (U/L) after parenteral nutrition administration
Time frame: 3 month
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Group | Assessment of Alanine Aminotransferase (ALT) | before enrollment | 16.3 U/L | Standard Deviation 12.8 |
| Study Group | Assessment of Alanine Aminotransferase (ALT) | week 1 | 14.7 U/L | Standard Deviation 7.8 |
| Study Group | Assessment of Alanine Aminotransferase (ALT) | week 2 | 17.1 U/L | Standard Deviation 8.7 |
| Study Group | Assessment of Alanine Aminotransferase (ALT) | week 3 | 17.5 U/L | Standard Deviation 6.8 |
| Control Group | Assessment of Alanine Aminotransferase (ALT) | week 3 | 17.7 U/L | Standard Deviation 7.9 |
| Control Group | Assessment of Alanine Aminotransferase (ALT) | before enrollment | 15.1 U/L | Standard Deviation 7.1 |
| Control Group | Assessment of Alanine Aminotransferase (ALT) | week 2 | 19.8 U/L | Standard Deviation 13.3 |
| Control Group | Assessment of Alanine Aminotransferase (ALT) | week 1 | 15.1 U/L | Standard Deviation 7.2 |
Secondary
Assessment of Aspartate Aminotransferase (AST)
blood samples were obtained before enrollment, week 1, 2 and 3 (U/L) after parenteral nutrition administration
Time frame: 3 month
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Group | Assessment of Aspartate Aminotransferase (AST) | before enrollment | 61.8 U/L | Standard Deviation 21.6 |
| Study Group | Assessment of Aspartate Aminotransferase (AST) | week 2 | 26.2 U/L | Standard Deviation 8 |
| Study Group | Assessment of Aspartate Aminotransferase (AST) | week 1 | 26.5 U/L | Standard Deviation 22 |
| Study Group | Assessment of Aspartate Aminotransferase (AST) | week 3 | 24.2 U/L | Standard Deviation 3.7 |
| Control Group | Assessment of Aspartate Aminotransferase (AST) | week 1 | 26.0 U/L | Standard Deviation 9.6 |
| Control Group | Assessment of Aspartate Aminotransferase (AST) | before enrollment | 55.6 U/L | Standard Deviation 28.1 |
| Control Group | Assessment of Aspartate Aminotransferase (AST) | week 3 | 25.9 U/L | Standard Deviation 8.8 |
| Control Group | Assessment of Aspartate Aminotransferase (AST) | week 2 | 24.4 U/L | Standard Deviation 6.2 |
Secondary
Assessment of Gamma Glutamyltranspeptidase (GGT)
blood samples were obtained before enrollment, week 1, 2 and 3 (U/L) after parenteral nutrition administration
Time frame: 3 month
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Group | Assessment of Gamma Glutamyltranspeptidase (GGT) | week 3 | 94.0 U/L | Standard Deviation 68.3 |
| Study Group | Assessment of Gamma Glutamyltranspeptidase (GGT) | before enrollment | 134.7 U/L | Standard Deviation 113.8 |
| Study Group | Assessment of Gamma Glutamyltranspeptidase (GGT) | week 1 | 73.8 U/L | Standard Deviation 58.8 |
| Study Group | Assessment of Gamma Glutamyltranspeptidase (GGT) | week 2 | 63.1 U/L | Standard Deviation 47.5 |
| Control Group | Assessment of Gamma Glutamyltranspeptidase (GGT) | week 2 | 68.6 U/L | Standard Deviation 43.5 |
| Control Group | Assessment of Gamma Glutamyltranspeptidase (GGT) | week 3 | 95.4 U/L | Standard Deviation 85.2 |
| Control Group | Assessment of Gamma Glutamyltranspeptidase (GGT) | week 1 | 79.5 U/L | Standard Deviation 45.4 |
| Control Group | Assessment of Gamma Glutamyltranspeptidase (GGT) | before enrollment | 138.7 U/L | Standard Deviation 62.6 |
Secondary
Head Circumference Gain
in-hospital head circumference gain at birth until discharge (cm/week)
Time frame: up to 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Head Circumference Gain | 0.7 cm/week | Standard Deviation 0.2 |
| Control Group | Head Circumference Gain | 0.7 cm/week | Standard Deviation 0.2 |
Secondary
Height Gain
in-hospital height gain at birth until discharge (cm/week)
Time frame: up to 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Height Gain | 0.9 cm/week | Standard Deviation 0.2 |
| Control Group | Height Gain | 0.8 cm/week | Standard Deviation 0.2 |
Secondary
Incidence of Extrauterine Growth Restriction (EUGR)
weight that is less than the tenth percentile for corrected gestational age by the time of discharge
Time frame: up to 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study Group | Incidence of Extrauterine Growth Restriction (EUGR) | 8 Participants |
| Control Group | Incidence of Extrauterine Growth Restriction (EUGR) | 12 Participants |
Secondary
Neonatal Morbidities
retinopathy of prematurity, bronchopulmonary dysplasia
Time frame: 4 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Study Group | Neonatal Morbidities | retinopathy of prematurity | 7 Participants |
| Study Group | Neonatal Morbidities | bronchopulmonary dysplasia | 10 Participants |
| Control Group | Neonatal Morbidities | retinopathy of prematurity | 6 Participants |
| Control Group | Neonatal Morbidities | bronchopulmonary dysplasia | 9 Participants |
Secondary
Weight Gain
in-hospital weight gain at birth until discharge (gram/day)
Time frame: up to 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Weight Gain | 19.7 gram/day | Standard Deviation 3.9 |
| Control Group | Weight Gain | 18.8 gram/day | Standard Deviation 3.9 |