Trial Outcomes & Findings for A Randomized, Double-Blinded, Placebo-Controlled Trial of Corticosteroid Therapy Following Portoenterostomy (NCT NCT00294684)
NCT ID: NCT00294684
Last Updated: 2019-10-22
Results Overview
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
141 participants
Primary outcome timeframe
Measurements will be made at 6 months after portoenterostomy
Results posted on
2019-10-22
Participant Flow
One patient was enrolled but not randomized. Therefore, the overall number enrolled is 141, while the number randomized and starting participant flow is 140.
Participant milestones
| Measure |
Corticosteroids
Corticosteroids: Schedule and dosing of corticosteroids following portoenterostomy in infants with biliary atresia are listed below.
Days 1-3: Methylprednisolone, IV-4mg/kg/day, divided BID Days 4-7: Prednisolone, PO-4mg/kg/day, divided BID Week 2: 4 mg/kg/day, divided BID Week 3: 2 mg/kg/day, divided BID Week 4: 2 mg/kg/day, divided BID Week 5: 1 mg/kg/day, once a day Week 6: 1 mg/kg/day, once a day Week 7: 0.8 mg/kg/day, once a day Week 8: 0.6 mg/kg/day, once a day Week 9: 0.4 mg/kg/day, once a day Week 10: 0.2 mg/kg/day, once a day Week 11: 0.1 mg/kg/day, once a day Week 12-13: 0.1 mg/kg/day, every other day Week 14: Stop
|
Placebo
Placebo: Schedule and dosing of placebo following portoenterostomy in infants with biliary atresia:
Days 1-3: IV - normal saline 4 mg/kg/day, divided BID Days 4-7: PO placebo 4 mg/kg/day, divided BID Week 2: PO placebo 4 mg/kg/day, divided BID Week 3: PO placebo 2 mg/kg/day, divided BID Week 4: PO placebo 2 mg/kg/day, divided BID Week 5: PO placebo 1 mg/kg/day, once a day Week 6: PO placebo 1 mg/kg/day, once a day Week 7: PO placebo 0.8 mg/kg/day, once a day Week 8: PO placebo 0.6 mg/kg/day, once a day Week 9: PO placebo 0.4 mg/kg/day, once a day Week 10: PO placebo 0.2 mg/kg/day, once a day Week 11: PO placebo 0.1 mg/kg/day, once a day Week 12-13: PO placebo 0.1 mg/kg/day, once a day every other day Week 14: Stop
|
|---|---|---|
|
Overall Study
STARTED
|
70
|
70
|
|
Overall Study
COMPLETED
|
65
|
62
|
|
Overall Study
NOT COMPLETED
|
5
|
8
|
Reasons for withdrawal
| Measure |
Corticosteroids
Corticosteroids: Schedule and dosing of corticosteroids following portoenterostomy in infants with biliary atresia are listed below.
Days 1-3: Methylprednisolone, IV-4mg/kg/day, divided BID Days 4-7: Prednisolone, PO-4mg/kg/day, divided BID Week 2: 4 mg/kg/day, divided BID Week 3: 2 mg/kg/day, divided BID Week 4: 2 mg/kg/day, divided BID Week 5: 1 mg/kg/day, once a day Week 6: 1 mg/kg/day, once a day Week 7: 0.8 mg/kg/day, once a day Week 8: 0.6 mg/kg/day, once a day Week 9: 0.4 mg/kg/day, once a day Week 10: 0.2 mg/kg/day, once a day Week 11: 0.1 mg/kg/day, once a day Week 12-13: 0.1 mg/kg/day, every other day Week 14: Stop
|
Placebo
Placebo: Schedule and dosing of placebo following portoenterostomy in infants with biliary atresia:
Days 1-3: IV - normal saline 4 mg/kg/day, divided BID Days 4-7: PO placebo 4 mg/kg/day, divided BID Week 2: PO placebo 4 mg/kg/day, divided BID Week 3: PO placebo 2 mg/kg/day, divided BID Week 4: PO placebo 2 mg/kg/day, divided BID Week 5: PO placebo 1 mg/kg/day, once a day Week 6: PO placebo 1 mg/kg/day, once a day Week 7: PO placebo 0.8 mg/kg/day, once a day Week 8: PO placebo 0.6 mg/kg/day, once a day Week 9: PO placebo 0.4 mg/kg/day, once a day Week 10: PO placebo 0.2 mg/kg/day, once a day Week 11: PO placebo 0.1 mg/kg/day, once a day Week 12-13: PO placebo 0.1 mg/kg/day, once a day every other day Week 14: Stop
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
5
|
8
|
Baseline Characteristics
A Randomized, Double-Blinded, Placebo-Controlled Trial of Corticosteroid Therapy Following Portoenterostomy
Baseline characteristics by cohort
| Measure |
Corticosteroids
n=70 Participants
Corticosteroids: Schedule and dosing of corticosteroids following portoenterostomy in infants with biliary atresia are listed below.
Days 1-3: Methylprednisolone, IV-4mg/kg/day, divided BID Days 4-7: Prednisolone, PO-4mg/kg/day, divided BID Week 2: 4 mg/kg/day, divided BID Week 3: 2 mg/kg/day, divided BID Week 4: 2 mg/kg/day, divided BID Week 5: 1 mg/kg/day, once a day Week 6: 1 mg/kg/day, once a day Week 7: 0.8 mg/kg/day, once a day Week 8: 0.6 mg/kg/day, once a day Week 9: 0.4 mg/kg/day, once a day Week 10: 0.2 mg/kg/day, once a day Week 11: 0.1 mg/kg/day, once a day Week 12-13: 0.1 mg/kg/day, every other day Week 14: Stop
|
Placebo
n=70 Participants
Placebo: Schedule and dosing of placebo following portoenterostomy in infants with biliary atresia:
Days 1-3: IV - normal saline 4 mg/kg/day, divided BID Days 4-7: PO placebo 4 mg/kg/day, divided BID Week 2: PO placebo 4 mg/kg/day, divided BID Week 3: PO placebo 2 mg/kg/day, divided BID Week 4: PO placebo 2 mg/kg/day, divided BID Week 5: PO placebo 1 mg/kg/day, once a day Week 6: PO placebo 1 mg/kg/day, once a day Week 7: PO placebo 0.8 mg/kg/day, once a day Week 8: PO placebo 0.6 mg/kg/day, once a day Week 9: PO placebo 0.4 mg/kg/day, once a day Week 10: PO placebo 0.2 mg/kg/day, once a day Week 11: PO placebo 0.1 mg/kg/day, once a day Week 12-13: PO placebo 0.1 mg/kg/day, once a day every other day Week 14: Stop
|
Total
n=140 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
2.3 Months
STANDARD_DEVIATION .93 • n=5 Participants
|
2.3 Months
STANDARD_DEVIATION .84 • n=7 Participants
|
2.3 Months
STANDARD_DEVIATION .89 • n=5 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
72 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
38 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
68 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
14 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
55 Participants
n=5 Participants
|
48 Participants
n=7 Participants
|
103 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
8 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
46 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
90 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
16 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Biliary atresia splenic malformation (BASM)
BASM
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Biliary atresia splenic malformation (BASM)
Not BASM
|
68 participants
n=5 Participants
|
67 participants
n=7 Participants
|
135 participants
n=5 Participants
|
|
OHI Main Type
I
|
5 participants
n=5 Participants
|
8 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
OHI Main Type
II
|
1 participants
n=5 Participants
|
4 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
OHI Main Type
III
|
64 participants
n=5 Participants
|
57 participants
n=7 Participants
|
121 participants
n=5 Participants
|
|
OHI Main Type
Missing
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Total Bilirubin
|
7.5 mg/dL
STANDARD_DEVIATION 2.6 • n=5 Participants
|
7.9 mg/dL
STANDARD_DEVIATION 2.8 • n=7 Participants
|
7.7 mg/dL
STANDARD_DEVIATION 2.7 • n=5 Participants
|
|
Length Z Score
|
-0.7 Z-Score
STANDARD_DEVIATION 1.35 • n=5 Participants
|
-0.6 Z-Score
STANDARD_DEVIATION 1.35 • n=7 Participants
|
-0.65 Z-Score
STANDARD_DEVIATION 1.35 • n=5 Participants
|
|
Weight Z Score
|
-0.8 Z-Score
STANDARD_DEVIATION 1.07 • n=5 Participants
|
-0.8 Z-Score
STANDARD_DEVIATION 1.06 • n=7 Participants
|
-0.8 Z-Score
STANDARD_DEVIATION 1.07 • n=5 Participants
|
PRIMARY outcome
Timeframe: Measurements will be made at 6 months after portoenterostomyPopulation: Intent to Treat
Outcome measures
| Measure |
Corticosteroids
n=70 Participants
Corticosteroids: Schedule and dosing of corticosteroids following portoenterostomy in infants with biliary atresia are listed below.
Days 1-3: Methylprednisolone, IV-4mg/kg/day, divided BID Days 4-7: Prednisolone, PO-4mg/kg/day, divided BID Week 2: 4 mg/kg/day, divided BID Week 3: 2 mg/kg/day, divided BID Week 4: 2 mg/kg/day, divided BID Week 5: 1 mg/kg/day, once a day Week 6: 1 mg/kg/day, once a day Week 7: 0.8 mg/kg/day, once a day Week 8: 0.6 mg/kg/day, once a day Week 9: 0.4 mg/kg/day, once a day Week 10: 0.2 mg/kg/day, once a day Week 11: 0.1 mg/kg/day, once a day Week 12-13: 0.1 mg/kg/day, every other day Week 14: Stop
|
Placebo
n=70 Participants
Placebo: Schedule and dosing of placebo following portoenterostomy in infants with biliary atresia:
Days 1-3: IV - normal saline 4 mg/kg/day, divided BID Days 4-7: PO placebo 4 mg/kg/day, divided BID Week 2: PO placebo 4 mg/kg/day, divided BID Week 3: PO placebo 2 mg/kg/day, divided BID Week 4: PO placebo 2 mg/kg/day, divided BID Week 5: PO placebo 1 mg/kg/day, once a day Week 6: PO placebo 1 mg/kg/day, once a day Week 7: PO placebo 0.8 mg/kg/day, once a day Week 8: PO placebo 0.6 mg/kg/day, once a day Week 9: PO placebo 0.4 mg/kg/day, once a day Week 10: PO placebo 0.2 mg/kg/day, once a day Week 11: PO placebo 0.1 mg/kg/day, once a day Week 12-13: PO placebo 0.1 mg/kg/day, once a day every other day Week 14: Stop
|
|---|---|---|
|
The Percentage of Patients With Serum Total Bilirubin <1.5 mg/dL and With Native Liver at 6 Months After Portoenterostomy
|
58.6 percentage of participants
|
48.6 percentage of participants
|
SECONDARY outcome
Timeframe: Measurements will be made at 24 months of agePopulation: Intent to Treat
Outcome measures
| Measure |
Corticosteroids
n=70 Participants
Corticosteroids: Schedule and dosing of corticosteroids following portoenterostomy in infants with biliary atresia are listed below.
Days 1-3: Methylprednisolone, IV-4mg/kg/day, divided BID Days 4-7: Prednisolone, PO-4mg/kg/day, divided BID Week 2: 4 mg/kg/day, divided BID Week 3: 2 mg/kg/day, divided BID Week 4: 2 mg/kg/day, divided BID Week 5: 1 mg/kg/day, once a day Week 6: 1 mg/kg/day, once a day Week 7: 0.8 mg/kg/day, once a day Week 8: 0.6 mg/kg/day, once a day Week 9: 0.4 mg/kg/day, once a day Week 10: 0.2 mg/kg/day, once a day Week 11: 0.1 mg/kg/day, once a day Week 12-13: 0.1 mg/kg/day, every other day Week 14: Stop
|
Placebo
n=70 Participants
Placebo: Schedule and dosing of placebo following portoenterostomy in infants with biliary atresia:
Days 1-3: IV - normal saline 4 mg/kg/day, divided BID Days 4-7: PO placebo 4 mg/kg/day, divided BID Week 2: PO placebo 4 mg/kg/day, divided BID Week 3: PO placebo 2 mg/kg/day, divided BID Week 4: PO placebo 2 mg/kg/day, divided BID Week 5: PO placebo 1 mg/kg/day, once a day Week 6: PO placebo 1 mg/kg/day, once a day Week 7: PO placebo 0.8 mg/kg/day, once a day Week 8: PO placebo 0.6 mg/kg/day, once a day Week 9: PO placebo 0.4 mg/kg/day, once a day Week 10: PO placebo 0.2 mg/kg/day, once a day Week 11: PO placebo 0.1 mg/kg/day, once a day Week 12-13: PO placebo 0.1 mg/kg/day, once a day every other day Week 14: Stop
|
|---|---|---|
|
Survival With Native Liver at 24 Months of Age
|
58.7 percentage of participants
|
59.4 percentage of participants
|
SECONDARY outcome
Timeframe: Measurements will be made at 3 months after portoenterostomyPopulation: Intent to treat patients with 3 month bilirubin available are analyzed. There are no imputations for unobserved data. Patients with missing data are simply not included.
Outcome measures
| Measure |
Corticosteroids
n=63 Participants
Corticosteroids: Schedule and dosing of corticosteroids following portoenterostomy in infants with biliary atresia are listed below.
Days 1-3: Methylprednisolone, IV-4mg/kg/day, divided BID Days 4-7: Prednisolone, PO-4mg/kg/day, divided BID Week 2: 4 mg/kg/day, divided BID Week 3: 2 mg/kg/day, divided BID Week 4: 2 mg/kg/day, divided BID Week 5: 1 mg/kg/day, once a day Week 6: 1 mg/kg/day, once a day Week 7: 0.8 mg/kg/day, once a day Week 8: 0.6 mg/kg/day, once a day Week 9: 0.4 mg/kg/day, once a day Week 10: 0.2 mg/kg/day, once a day Week 11: 0.1 mg/kg/day, once a day Week 12-13: 0.1 mg/kg/day, every other day Week 14: Stop
|
Placebo
n=65 Participants
Placebo: Schedule and dosing of placebo following portoenterostomy in infants with biliary atresia:
Days 1-3: IV - normal saline 4 mg/kg/day, divided BID Days 4-7: PO placebo 4 mg/kg/day, divided BID Week 2: PO placebo 4 mg/kg/day, divided BID Week 3: PO placebo 2 mg/kg/day, divided BID Week 4: PO placebo 2 mg/kg/day, divided BID Week 5: PO placebo 1 mg/kg/day, once a day Week 6: PO placebo 1 mg/kg/day, once a day Week 7: PO placebo 0.8 mg/kg/day, once a day Week 8: PO placebo 0.6 mg/kg/day, once a day Week 9: PO placebo 0.4 mg/kg/day, once a day Week 10: PO placebo 0.2 mg/kg/day, once a day Week 11: PO placebo 0.1 mg/kg/day, once a day Week 12-13: PO placebo 0.1 mg/kg/day, once a day every other day Week 14: Stop
|
|---|---|---|
|
Serum Total Bilirubin Concentration
|
3.5 mg/dL
Standard Deviation 5.32
|
5.1 mg/dL
Standard Deviation 6.15
|
SECONDARY outcome
Timeframe: 12 Months post HPEPopulation: Intent to treat patients with 12 month bilirubin available are analyzed. There are no imputations for unobserved data. Patients with missing data are simply not included.
Outcome measures
| Measure |
Corticosteroids
n=41 Participants
Corticosteroids: Schedule and dosing of corticosteroids following portoenterostomy in infants with biliary atresia are listed below.
Days 1-3: Methylprednisolone, IV-4mg/kg/day, divided BID Days 4-7: Prednisolone, PO-4mg/kg/day, divided BID Week 2: 4 mg/kg/day, divided BID Week 3: 2 mg/kg/day, divided BID Week 4: 2 mg/kg/day, divided BID Week 5: 1 mg/kg/day, once a day Week 6: 1 mg/kg/day, once a day Week 7: 0.8 mg/kg/day, once a day Week 8: 0.6 mg/kg/day, once a day Week 9: 0.4 mg/kg/day, once a day Week 10: 0.2 mg/kg/day, once a day Week 11: 0.1 mg/kg/day, once a day Week 12-13: 0.1 mg/kg/day, every other day Week 14: Stop
|
Placebo
n=36 Participants
Placebo: Schedule and dosing of placebo following portoenterostomy in infants with biliary atresia:
Days 1-3: IV - normal saline 4 mg/kg/day, divided BID Days 4-7: PO placebo 4 mg/kg/day, divided BID Week 2: PO placebo 4 mg/kg/day, divided BID Week 3: PO placebo 2 mg/kg/day, divided BID Week 4: PO placebo 2 mg/kg/day, divided BID Week 5: PO placebo 1 mg/kg/day, once a day Week 6: PO placebo 1 mg/kg/day, once a day Week 7: PO placebo 0.8 mg/kg/day, once a day Week 8: PO placebo 0.6 mg/kg/day, once a day Week 9: PO placebo 0.4 mg/kg/day, once a day Week 10: PO placebo 0.2 mg/kg/day, once a day Week 11: PO placebo 0.1 mg/kg/day, once a day Week 12-13: PO placebo 0.1 mg/kg/day, once a day every other day Week 14: Stop
|
|---|---|---|
|
Total Bilirubin Concentration at 12 Months
|
1.7 mg/dL
Standard Deviation 3.63
|
3.7 mg/dL
Standard Deviation 6.63
|
SECONDARY outcome
Timeframe: At 24 Months of AgePopulation: Intent to treat patients with 24 month bilirubin available are analyzed. There are no imputations for unobserved data. Patients with missing data are simply not included.
Outcome measures
| Measure |
Corticosteroids
n=35 Participants
Corticosteroids: Schedule and dosing of corticosteroids following portoenterostomy in infants with biliary atresia are listed below.
Days 1-3: Methylprednisolone, IV-4mg/kg/day, divided BID Days 4-7: Prednisolone, PO-4mg/kg/day, divided BID Week 2: 4 mg/kg/day, divided BID Week 3: 2 mg/kg/day, divided BID Week 4: 2 mg/kg/day, divided BID Week 5: 1 mg/kg/day, once a day Week 6: 1 mg/kg/day, once a day Week 7: 0.8 mg/kg/day, once a day Week 8: 0.6 mg/kg/day, once a day Week 9: 0.4 mg/kg/day, once a day Week 10: 0.2 mg/kg/day, once a day Week 11: 0.1 mg/kg/day, once a day Week 12-13: 0.1 mg/kg/day, every other day Week 14: Stop
|
Placebo
n=30 Participants
Placebo: Schedule and dosing of placebo following portoenterostomy in infants with biliary atresia:
Days 1-3: IV - normal saline 4 mg/kg/day, divided BID Days 4-7: PO placebo 4 mg/kg/day, divided BID Week 2: PO placebo 4 mg/kg/day, divided BID Week 3: PO placebo 2 mg/kg/day, divided BID Week 4: PO placebo 2 mg/kg/day, divided BID Week 5: PO placebo 1 mg/kg/day, once a day Week 6: PO placebo 1 mg/kg/day, once a day Week 7: PO placebo 0.8 mg/kg/day, once a day Week 8: PO placebo 0.6 mg/kg/day, once a day Week 9: PO placebo 0.4 mg/kg/day, once a day Week 10: PO placebo 0.2 mg/kg/day, once a day Week 11: PO placebo 0.1 mg/kg/day, once a day Week 12-13: PO placebo 0.1 mg/kg/day, once a day every other day Week 14: Stop
|
|---|---|---|
|
Total Bilirubin Concentration at 24 Months of Age
|
1.3 mg/dL
Standard Deviation 3.37
|
1.6 mg/dL
Standard Deviation 3.73
|
SECONDARY outcome
Timeframe: HPE until 24 months of ageweight for age Z-score (in subjects without ascites) over the course of the study
Outcome measures
| Measure |
Corticosteroids
n=70 Participants
Corticosteroids: Schedule and dosing of corticosteroids following portoenterostomy in infants with biliary atresia are listed below.
Days 1-3: Methylprednisolone, IV-4mg/kg/day, divided BID Days 4-7: Prednisolone, PO-4mg/kg/day, divided BID Week 2: 4 mg/kg/day, divided BID Week 3: 2 mg/kg/day, divided BID Week 4: 2 mg/kg/day, divided BID Week 5: 1 mg/kg/day, once a day Week 6: 1 mg/kg/day, once a day Week 7: 0.8 mg/kg/day, once a day Week 8: 0.6 mg/kg/day, once a day Week 9: 0.4 mg/kg/day, once a day Week 10: 0.2 mg/kg/day, once a day Week 11: 0.1 mg/kg/day, once a day Week 12-13: 0.1 mg/kg/day, every other day Week 14: Stop
|
Placebo
n=70 Participants
Placebo: Schedule and dosing of placebo following portoenterostomy in infants with biliary atresia:
Days 1-3: IV - normal saline 4 mg/kg/day, divided BID Days 4-7: PO placebo 4 mg/kg/day, divided BID Week 2: PO placebo 4 mg/kg/day, divided BID Week 3: PO placebo 2 mg/kg/day, divided BID Week 4: PO placebo 2 mg/kg/day, divided BID Week 5: PO placebo 1 mg/kg/day, once a day Week 6: PO placebo 1 mg/kg/day, once a day Week 7: PO placebo 0.8 mg/kg/day, once a day Week 8: PO placebo 0.6 mg/kg/day, once a day Week 9: PO placebo 0.4 mg/kg/day, once a day Week 10: PO placebo 0.2 mg/kg/day, once a day Week 11: PO placebo 0.1 mg/kg/day, once a day Week 12-13: PO placebo 0.1 mg/kg/day, once a day every other day Week 14: Stop
|
|---|---|---|
|
Weight Z-Score
|
-0.8 Z-score
Standard Error 0.13
|
-0.8 Z-score
Standard Error 0.13
|
SECONDARY outcome
Timeframe: HPE to age 24 MonthsHeight by Age Z-score over the course of the study
Outcome measures
| Measure |
Corticosteroids
n=70 Participants
Corticosteroids: Schedule and dosing of corticosteroids following portoenterostomy in infants with biliary atresia are listed below.
Days 1-3: Methylprednisolone, IV-4mg/kg/day, divided BID Days 4-7: Prednisolone, PO-4mg/kg/day, divided BID Week 2: 4 mg/kg/day, divided BID Week 3: 2 mg/kg/day, divided BID Week 4: 2 mg/kg/day, divided BID Week 5: 1 mg/kg/day, once a day Week 6: 1 mg/kg/day, once a day Week 7: 0.8 mg/kg/day, once a day Week 8: 0.6 mg/kg/day, once a day Week 9: 0.4 mg/kg/day, once a day Week 10: 0.2 mg/kg/day, once a day Week 11: 0.1 mg/kg/day, once a day Week 12-13: 0.1 mg/kg/day, every other day Week 14: Stop
|
Placebo
n=70 Participants
Placebo: Schedule and dosing of placebo following portoenterostomy in infants with biliary atresia:
Days 1-3: IV - normal saline 4 mg/kg/day, divided BID Days 4-7: PO placebo 4 mg/kg/day, divided BID Week 2: PO placebo 4 mg/kg/day, divided BID Week 3: PO placebo 2 mg/kg/day, divided BID Week 4: PO placebo 2 mg/kg/day, divided BID Week 5: PO placebo 1 mg/kg/day, once a day Week 6: PO placebo 1 mg/kg/day, once a day Week 7: PO placebo 0.8 mg/kg/day, once a day Week 8: PO placebo 0.6 mg/kg/day, once a day Week 9: PO placebo 0.4 mg/kg/day, once a day Week 10: PO placebo 0.2 mg/kg/day, once a day Week 11: PO placebo 0.1 mg/kg/day, once a day Week 12-13: PO placebo 0.1 mg/kg/day, once a day every other day Week 14: Stop
|
|---|---|---|
|
Height Z-Score
|
-0.7 Z-score
Standard Error 0.16
|
-0.6 Z-score
Standard Error 0.16
|
SECONDARY outcome
Timeframe: 12 MonthsPopulation: Participants with their native liver at 12 months
Outcome measures
| Measure |
Corticosteroids
n=52 Participants
Corticosteroids: Schedule and dosing of corticosteroids following portoenterostomy in infants with biliary atresia are listed below.
Days 1-3: Methylprednisolone, IV-4mg/kg/day, divided BID Days 4-7: Prednisolone, PO-4mg/kg/day, divided BID Week 2: 4 mg/kg/day, divided BID Week 3: 2 mg/kg/day, divided BID Week 4: 2 mg/kg/day, divided BID Week 5: 1 mg/kg/day, once a day Week 6: 1 mg/kg/day, once a day Week 7: 0.8 mg/kg/day, once a day Week 8: 0.6 mg/kg/day, once a day Week 9: 0.4 mg/kg/day, once a day Week 10: 0.2 mg/kg/day, once a day Week 11: 0.1 mg/kg/day, once a day Week 12-13: 0.1 mg/kg/day, every other day Week 14: Stop
|
Placebo
n=47 Participants
Placebo: Schedule and dosing of placebo following portoenterostomy in infants with biliary atresia:
Days 1-3: IV - normal saline 4 mg/kg/day, divided BID Days 4-7: PO placebo 4 mg/kg/day, divided BID Week 2: PO placebo 4 mg/kg/day, divided BID Week 3: PO placebo 2 mg/kg/day, divided BID Week 4: PO placebo 2 mg/kg/day, divided BID Week 5: PO placebo 1 mg/kg/day, once a day Week 6: PO placebo 1 mg/kg/day, once a day Week 7: PO placebo 0.8 mg/kg/day, once a day Week 8: PO placebo 0.6 mg/kg/day, once a day Week 9: PO placebo 0.4 mg/kg/day, once a day Week 10: PO placebo 0.2 mg/kg/day, once a day Week 11: PO placebo 0.1 mg/kg/day, once a day Week 12-13: PO placebo 0.1 mg/kg/day, once a day every other day Week 14: Stop
|
|---|---|---|
|
Presence of Ascites at 12 Months
|
5 participants
|
3 participants
|
SECONDARY outcome
Timeframe: 24 MonthsPopulation: Participants with their native liver at 24 months
Outcome measures
| Measure |
Corticosteroids
n=42 Participants
Corticosteroids: Schedule and dosing of corticosteroids following portoenterostomy in infants with biliary atresia are listed below.
Days 1-3: Methylprednisolone, IV-4mg/kg/day, divided BID Days 4-7: Prednisolone, PO-4mg/kg/day, divided BID Week 2: 4 mg/kg/day, divided BID Week 3: 2 mg/kg/day, divided BID Week 4: 2 mg/kg/day, divided BID Week 5: 1 mg/kg/day, once a day Week 6: 1 mg/kg/day, once a day Week 7: 0.8 mg/kg/day, once a day Week 8: 0.6 mg/kg/day, once a day Week 9: 0.4 mg/kg/day, once a day Week 10: 0.2 mg/kg/day, once a day Week 11: 0.1 mg/kg/day, once a day Week 12-13: 0.1 mg/kg/day, every other day Week 14: Stop
|
Placebo
n=43 Participants
Placebo: Schedule and dosing of placebo following portoenterostomy in infants with biliary atresia:
Days 1-3: IV - normal saline 4 mg/kg/day, divided BID Days 4-7: PO placebo 4 mg/kg/day, divided BID Week 2: PO placebo 4 mg/kg/day, divided BID Week 3: PO placebo 2 mg/kg/day, divided BID Week 4: PO placebo 2 mg/kg/day, divided BID Week 5: PO placebo 1 mg/kg/day, once a day Week 6: PO placebo 1 mg/kg/day, once a day Week 7: PO placebo 0.8 mg/kg/day, once a day Week 8: PO placebo 0.6 mg/kg/day, once a day Week 9: PO placebo 0.4 mg/kg/day, once a day Week 10: PO placebo 0.2 mg/kg/day, once a day Week 11: PO placebo 0.1 mg/kg/day, once a day Week 12-13: PO placebo 0.1 mg/kg/day, once a day every other day Week 14: Stop
|
|---|---|---|
|
Presence of Ascites at 24 Months
|
1 participants
|
3 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 24 MonthsPopulation: Although the protocol specified analyses of serum biomarkers as secondary outcomes, the intent was to only perform these analyses if the primary endpoint showed sufficient efficacy. Given the lack of efficacy of steroids (vs placebo), the analyses of fat-soluble vitamins were not performed; thus, data are not summarized for this assessment.
Vitamin E sufficiency is measured as the ratio of serum vitamin E/total lipids
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 24 MonthsPopulation: Although the protocol specified analyses of serum biomarkers as secondary outcomes, the intent was to only perform these analyses if the primary endpoint showed sufficient efficacy. Given the lack of efficacy of steroids (vs placebo), the analyses of fat-soluble vitamins were not performed; thus, data are not summarized for this assessment.
Vitamin K sufficiency is measured by INR (international normalized ratio)
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 24 MonthsPopulation: Although the protocol specified analyses of serum biomarkers as secondary outcomes, the intent was to only perform these analyses if the primary endpoint showed sufficient efficacy. Given the lack of efficacy of steroids (vs placebo), the analyses of fat-soluble vitamins were not performed; thus, data are not summarized for this assessment.
Vitamin D sufficiency is measured by the serum level of 25-hydroxy vitamin D
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 24 monthsPopulation: Although the protocol specified analyses of serum biomarkers as secondary outcomes, the intent was to only perform these analyses if the primary endpoint showed sufficient efficacy. Given the lack of efficacy of steroids (vs placebo), the analyses of fat-soluble vitamins were not performed; thus, data are not summarized for this assessment.
Vitamin A sufficiency is defined as the molar ratio of serum retinol/retinol binding protein
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 MonthsPopulation: Although the protocol specified analyses of serum biomarkers as secondary outcomes, the intent was to only perform these analyses if the primary endpoint showed sufficient efficacy. Given the lack of efficacy of steroids (vs placebo), the analyses of fat-soluble vitamins were not performed; thus, data are not summarized for this assessment.
Vitamin D sufficiency is measured by the serum level of 25-hydroxy vitamin D
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 MonthsPopulation: Although the protocol specified analyses of serum biomarkers as secondary outcomes, the intent was to only perform these analyses if the primary endpoint showed sufficient efficacy. Given the lack of efficacy of steroids (vs placebo), the analyses of fat-soluble vitamins were not performed; thus, data are not summarized for this assessment.
Vitamin K sufficiency is measured by INR (international normalized ratio)
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 MonthsPopulation: Although the protocol specified analyses of serum biomarkers as secondary outcomes, the intent was to only perform these analyses if the primary endpoint showed sufficient efficacy. Given the lack of efficacy of steroids (vs placebo), the analyses of fat-soluble vitamins were not performed; thus, data are not summarized for this assessment.
Vitamin E sufficiency is measured as the ratio of serum vitamin E/total lipids
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 monthsPopulation: Although the protocol specified analyses of serum biomarkers as secondary outcomes, the intent was to only perform these analyses if the primary endpoint showed sufficient efficacy. Given the lack of efficacy of steroids (vs placebo), the analyses of fat-soluble vitamins were not performed; thus, data are not summarized for this assessment.
Vitamin A sufficiency is measured by the molar ratio of serum retinol/retinol binding protein
Outcome measures
Outcome data not reported
Adverse Events
Corticosteroids
Serious events: 57 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo
Serious events: 56 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Corticosteroids
n=70 participants at risk
Corticosteroids: Schedule and dosing of corticosteroids following portoenterostomy in infants with biliary atresia are listed below.
Days 1-3: Methylprednisolone, IV-4mg/kg/day, divided BID Days 4-7: Prednisolone, PO-4mg/kg/day, divided BID Week 2: 4 mg/kg/day, divided BID Week 3: 2 mg/kg/day, divided BID Week 4: 2 mg/kg/day, divided BID Week 5: 1 mg/kg/day, once a day Week 6: 1 mg/kg/day, once a day Week 7: 0.8 mg/kg/day, once a day Week 8: 0.6 mg/kg/day, once a day Week 9: 0.4 mg/kg/day, once a day Week 10: 0.2 mg/kg/day, once a day Week 11: 0.1 mg/kg/day, once a day Week 12-13: 0.1 mg/kg/day, every other day Week 14: Stop
|
Placebo
n=70 participants at risk
Placebo: Schedule and dosing of placebo following portoenterostomy in infants with biliary atresia:
Days 1-3: IV - normal saline 4 mg/kg/day, divided BID Days 4-7: PO placebo 4 mg/kg/day, divided BID Week 2: PO placebo 4 mg/kg/day, divided BID Week 3: PO placebo 2 mg/kg/day, divided BID Week 4: PO placebo 2 mg/kg/day, divided BID Week 5: PO placebo 1 mg/kg/day, once a day Week 6: PO placebo 1 mg/kg/day, once a day Week 7: PO placebo 0.8 mg/kg/day, once a day Week 8: PO placebo 0.6 mg/kg/day, once a day Week 9: PO placebo 0.4 mg/kg/day, once a day Week 10: PO placebo 0.2 mg/kg/day, once a day Week 11: PO placebo 0.1 mg/kg/day, once a day Week 12-13: PO placebo 0.1 mg/kg/day, once a day every other day Week 14: Stop
|
|---|---|---|
|
Congenital, familial and genetic disorders
Congenital
|
1.4%
1/70 • Number of events 1 • Up to 24 months of age
|
1.4%
1/70 • Number of events 1 • Up to 24 months of age
|
|
Gastrointestinal disorders
Gastrointestinal
|
7.1%
5/70 • Number of events 6 • Up to 24 months of age
|
4.3%
3/70 • Number of events 3 • Up to 24 months of age
|
|
Hepatobiliary disorders
Hepatic
|
31.4%
22/70 • Number of events 41 • Up to 24 months of age
|
22.9%
16/70 • Number of events 30 • Up to 24 months of age
|
|
Immune system disorders
Immunological
|
1.4%
1/70 • Number of events 1 • Up to 24 months of age
|
0.00%
0/70 • Up to 24 months of age
|
|
Infections and infestations
Infectious
|
71.4%
50/70 • Number of events 129 • Up to 24 months of age
|
65.7%
46/70 • Number of events 109 • Up to 24 months of age
|
|
Metabolism and nutrition disorders
Metabolic
|
1.4%
1/70 • Number of events 1 • Up to 24 months of age
|
1.4%
1/70 • Number of events 2 • Up to 24 months of age
|
|
General disorders
Miscellaneous
|
4.3%
3/70 • Number of events 5 • Up to 24 months of age
|
1.4%
1/70 • Number of events 1 • Up to 24 months of age
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplastic
|
1.4%
1/70 • Number of events 1 • Up to 24 months of age
|
0.00%
0/70 • Up to 24 months of age
|
|
Nervous system disorders
Neurological
|
1.4%
1/70 • Number of events 1 • Up to 24 months of age
|
0.00%
0/70 • Up to 24 months of age
|
|
Metabolism and nutrition disorders
Nutritional
|
10.0%
7/70 • Number of events 8 • Up to 24 months of age
|
12.9%
9/70 • Number of events 11 • Up to 24 months of age
|
|
Musculoskeletal and connective tissue disorders
Orthopedic
|
2.9%
2/70 • Number of events 2 • Up to 24 months of age
|
2.9%
2/70 • Number of events 2 • Up to 24 months of age
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary
|
0.00%
0/70 • Up to 24 months of age
|
1.4%
1/70 • Number of events 1 • Up to 24 months of age
|
|
Surgical and medical procedures
Surgical
|
10.0%
7/70 • Number of events 8 • Up to 24 months of age
|
2.9%
2/70 • Number of events 2 • Up to 24 months of age
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER