Parenteral Nutrition Associated Cholestasis
Conditions
Brief summary
The Investigators hypothesize that increased cumulative amount of lipid intake causes PNAC in late preterm and term neonates with major GI surgical disorders
Interventions
DRUGintravenous lipid
intravenous given daily for 6 weeks
Sponsors
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Masking description
The care taker team provided daily weight to the research pharmacist for calculating the dose of the lipid according to the assignment and then calculated the rate of administration over 18 to 24 hours depending on the volume. The rate and dose was masked to the investigators and participants.
Eligibility
Sex/Gender
ALL
Age
No minimum to 72 Hours
Healthy volunteers
No
Inclusion criteria
All neonates ≥ 34 weeks gestational age with major GI surgical disorders (Gastroschisis, omphalocele, volvulus, trachea-esophageal fistula, duodenal atresia, jejunal atresia, ileal atresia, hirschsprung's disease, anorectal malformation, intestinal obstruction, and GI perforations) requiring surgery admitted to our NICU within first 72 hours will be eligible for this study
Exclusion criteria
1. If does not need TPN by 72 hours; 2. Direct hyperbilirubinemia within the first 72 hours after birth; 3. TORCH infections (Toxoplasmosis, CMV, Herpes, Rubella, HIV, etc); 4. Biliary tract disorders leading to direct hyperbilirubinemia; 5. Known metabolic disorders that may be associated with direct hyperbilirubinemia- such as Galactosemia, α-1 antitrypsin deficiency, etc
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Parenteral Nutrition Associated Cholestasis | 7 weeks | Defined as direct bilirubin ≥ 2mg/dl developing within one week of the completion of 6 week randomization period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Rate of Change in Direct Bilirubin | baseline, weeks 1, 2, 3, 4, 5 and 6 | Amount of direct (conjugated) bilirubin was measured from sera samples. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Dose Intravenous Lipids intravenous lipid: intravenous given daily for 6 weeks | 20 |
| High Dose of Intravenous Lipids intravenous lipid: intravenous given daily for 6 weeks | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Low Dose Intravenous Lipids | Total | High Dose of Intravenous Lipids |
|---|---|---|---|
| Age, Continuous | 37.9 weeks STANDARD_DEVIATION 1.1 | 37.0 weeks STANDARD_DEVIATION 1.3 | 36.7 weeks STANDARD_DEVIATION 1.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 9 Participants | 5 Participants |
| Race (NIH/OMB) White | 16 Participants | 31 Participants | 15 Participants |
| Region of Enrollment United States | 20 participants | 40 participants | 20 participants |
| Sex: Female, Male Female | 9 Participants | 22 Participants | 13 Participants |
| Sex: Female, Male Male | 11 Participants | 18 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Number of Participants With Parenteral Nutrition Associated Cholestasis
Defined as direct bilirubin ≥ 2mg/dl developing within one week of the completion of 6 week randomization period
Time frame: 7 weeks
Population: Intent to treat analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose Intravenous Lipids | Number of Participants With Parenteral Nutrition Associated Cholestasis | 6 Participants |
| High Dose of Intravenous Lipids | Number of Participants With Parenteral Nutrition Associated Cholestasis | 6 Participants |
Comparison: we hypothesized that among ≥ 34 weeks GA infants with GISDs, infants receiving 1g/kg/day S-ILE (lipid minimizing strategy) would have decreased incidence of IFALD compared to those receiving 2g/kg/day S-ILE. We also hypothesized that the rate of rise of DB would be lower among ≥ 34 weeks GA infants with GISDs receiving 1g/kg/day versus 2g/kg/day of S-ILE.p-value: 0.94Chi-squared
Secondary
Mean Rate of Change in Direct Bilirubin
Amount of direct (conjugated) bilirubin was measured from sera samples.
Time frame: baseline, weeks 1, 2, 3, 4, 5 and 6
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low Dose Intravenous Lipids | Mean Rate of Change in Direct Bilirubin | 0.16 mg/dL/week |
| High Dose of Intravenous Lipids | Mean Rate of Change in Direct Bilirubin | 0.19 mg/dL/week |
Comparison: We also hypothesized that the rate of rise of direct bilirubin would be lower among ≥ 34 weeks GA infants with GISDs receiving 1g/kg/day versus 2g/kg/day of S-ILE.p-value: 0.0005Mixed Models Analysis