Trial Outcomes & Findings for Primary Sclerosing Cholangitis With Oral Vancomycin by the Study of Its Antimicrobial and Immunomodulating Effects (NCT NCT01802073)
NCT ID: NCT01802073
Last Updated: 2018-09-21
Results Overview
Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Elevated ALT was any value greater than the upper limit of the standard reference range used by patient's laboratory.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
34 participants
Primary outcome timeframe
Baseline; Month 3
Results posted on
2018-09-21
Participant Flow
Two participants in the adult cohort completed the study but were not analyzed for outcomes (1 post-liver transplant patient; 1 completed the study but followed a diet that could influence results analysis). Two adult participants who consented but withdrew prior to treatment were not analyzed for outcomes.
Participant milestones
| Measure |
Oral Vancomycin-Children
For children who weight \< or = 30 kg, the vancomycin dose will be 50 mg/kg/day given orally 3 times per day for the 1st month and continue with the same dose for subsequent months if the clinical laboratory studies improved and are normal. If the laboratory studies are not normal the dose will be increased to 75 mg/kg/day given orally 3 times per day for the 2nd month and 100mg/kg/day given orally 3 times per day the 3rd month. If the laboratory studies do not improve by the end of the 3rd month since starting the vancomycin, the vancomycin will be stopped and the child will not continue the study.
Oral Vancomycin
|
Oral Vancomycin-Adults
For adults and children who weigh \>30 kg, the vancomycin dose will be 500 mg given orally 3 times per day for the 1st month and continue with this dose if the clinical laboratory studies improve and are normal. If the laboratory studies are not normal the dose will be increased to 750 mg 3 times per day for the 2nd month and 1000 mg 3 times per day the 3rd month.
Oral Vancomycin
|
|---|---|---|
|
Overall Study
STARTED
|
14
|
20
|
|
Overall Study
COMPLETED
|
9
|
9
|
|
Overall Study
NOT COMPLETED
|
5
|
11
|
Reasons for withdrawal
| Measure |
Oral Vancomycin-Children
For children who weight \< or = 30 kg, the vancomycin dose will be 50 mg/kg/day given orally 3 times per day for the 1st month and continue with the same dose for subsequent months if the clinical laboratory studies improved and are normal. If the laboratory studies are not normal the dose will be increased to 75 mg/kg/day given orally 3 times per day for the 2nd month and 100mg/kg/day given orally 3 times per day the 3rd month. If the laboratory studies do not improve by the end of the 3rd month since starting the vancomycin, the vancomycin will be stopped and the child will not continue the study.
Oral Vancomycin
|
Oral Vancomycin-Adults
For adults and children who weigh \>30 kg, the vancomycin dose will be 500 mg given orally 3 times per day for the 1st month and continue with this dose if the clinical laboratory studies improve and are normal. If the laboratory studies are not normal the dose will be increased to 750 mg 3 times per day for the 2nd month and 1000 mg 3 times per day the 3rd month.
Oral Vancomycin
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Non-compliant
|
4
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
|
Overall Study
Physician Decision
|
0
|
7
|
Baseline Characteristics
Primary Sclerosing Cholangitis With Oral Vancomycin by the Study of Its Antimicrobial and Immunomodulating Effects
Baseline characteristics by cohort
| Measure |
Oral Vancomycin-Children
n=14 Participants
For children who weight \< or = 30 kg, the vancomycin dose will be 50 mg/kg/day given orally 3 times per day for the 1st month and continue with the same dose for subsequent months if the clinical laboratory studies improved and are normal. If the laboratory studies are not normal the dose will be increased to 75 mg/kg/day given orally 3 times per day for the 2nd month and 100mg/kg/day given orally 3 times per day the 3rd month. If the laboratory studies do not improve by the end of the 3rd month since starting the vancomycin, the vancomycin will be stopped and the child will not continue the study.
Oral Vancomycin
|
Oral Vancomycin-Adults
n=20 Participants
For adults and children who weigh \>30 kg, the vancomycin dose will be 500 mg given orally 3 times per day for the 1st month and continue with this dose if the clinical laboratory studies improve and are normal. If the laboratory studies are not normal the dose will be increased to 750 mg 3 times per day for the 2nd month and 1000 mg 3 times per day the 3rd month.
Oral Vancomycin
|
Total
n=34 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
0-6 years
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Age, Customized
7-12 years
|
5 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Age, Customized
13-17 years
|
6 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Age, Customized
18-64 years
|
1 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline; Month 3Population: Participants with ALT elevated at baseline are included in the analysis.
Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Elevated ALT was any value greater than the upper limit of the standard reference range used by patient's laboratory.
Outcome measures
| Measure |
Oral Vancomycin-Children
n=10 Participants
For children who weight \< or = 30 kg, the vancomycin dose will be 50 mg/kg/day given orally 3 times per day for the 1st month and continue with the same dose for subsequent months if the clinical laboratory studies improved and are normal. If the laboratory studies are not normal the dose will be increased to 75 mg/kg/day given orally 3 times per day for the 2nd month and 100mg/kg/day given orally 3 times per day the 3rd month. If the laboratory studies do not improve by the end of the 3rd month since starting the vancomycin, the vancomycin will be stopped and the child will not continue the study.
Oral Vancomycin
|
Oral Vancomycin-Adults
n=9 Participants
For adults and children who weigh \>30 kg, the vancomycin dose will be 500 mg given orally 3 times per day for the 1st month and continue with this dose if the clinical laboratory studies improve and are normal. If the laboratory studies are not normal the dose will be increased to 750 mg 3 times per day for the 2nd month and 1000 mg 3 times per day the 3rd month.
Oral Vancomycin
|
|---|---|---|
|
Count of Participants With Elevated Alanine Aminotransferase (ALT) at Baseline and With Clinically Significant Improvement at Month 3
|
10 Participants
|
6 Participants
|
PRIMARY outcome
Timeframe: Baseline; Month 3Population: Participants with GGT elevated at baseline are included in the analysis.
Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Elevated GGT was any value greater than the upper limit of the standard reference range used by patient's laboratory.
Outcome measures
| Measure |
Oral Vancomycin-Children
n=8 Participants
For children who weight \< or = 30 kg, the vancomycin dose will be 50 mg/kg/day given orally 3 times per day for the 1st month and continue with the same dose for subsequent months if the clinical laboratory studies improved and are normal. If the laboratory studies are not normal the dose will be increased to 75 mg/kg/day given orally 3 times per day for the 2nd month and 100mg/kg/day given orally 3 times per day the 3rd month. If the laboratory studies do not improve by the end of the 3rd month since starting the vancomycin, the vancomycin will be stopped and the child will not continue the study.
Oral Vancomycin
|
Oral Vancomycin-Adults
n=9 Participants
For adults and children who weigh \>30 kg, the vancomycin dose will be 500 mg given orally 3 times per day for the 1st month and continue with this dose if the clinical laboratory studies improve and are normal. If the laboratory studies are not normal the dose will be increased to 750 mg 3 times per day for the 2nd month and 1000 mg 3 times per day the 3rd month.
Oral Vancomycin
|
|---|---|---|
|
Count of Participants With Elevated Gamma-glutamyltransferase (GGT) at Baseline and With Clinically Significant Improvement at Month 3
|
8 Participants
|
6 Participants
|
PRIMARY outcome
Timeframe: Baseline; Month 3Population: Participants with ALT and/or GGT elevated at baseline are included in the analysis.
Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Elevated ALT (and GGT) was any value greater than the upper limit of the standard reference range used by patient's laboratory.
Outcome measures
| Measure |
Oral Vancomycin-Children
n=10 Participants
For children who weight \< or = 30 kg, the vancomycin dose will be 50 mg/kg/day given orally 3 times per day for the 1st month and continue with the same dose for subsequent months if the clinical laboratory studies improved and are normal. If the laboratory studies are not normal the dose will be increased to 75 mg/kg/day given orally 3 times per day for the 2nd month and 100mg/kg/day given orally 3 times per day the 3rd month. If the laboratory studies do not improve by the end of the 3rd month since starting the vancomycin, the vancomycin will be stopped and the child will not continue the study.
Oral Vancomycin
|
Oral Vancomycin-Adults
n=10 Participants
For adults and children who weigh \>30 kg, the vancomycin dose will be 500 mg given orally 3 times per day for the 1st month and continue with this dose if the clinical laboratory studies improve and are normal. If the laboratory studies are not normal the dose will be increased to 750 mg 3 times per day for the 2nd month and 1000 mg 3 times per day the 3rd month.
Oral Vancomycin
|
|---|---|---|
|
Count of Participants With Elevated ALT and/or GGT at Baseline and With Clinically Significant Improvement at Month 3
|
10 Participants
|
8 Participants
|
PRIMARY outcome
Timeframe: Baseline; Year 1Population: Participants with abnormal MRCP at baseline are included in the analysis.
Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. MRCP imaging was abnormal if it included biliary beading, biliary strictures, dilated bile duct, and/or liver fibrosis.
Outcome measures
| Measure |
Oral Vancomycin-Children
n=8 Participants
For children who weight \< or = 30 kg, the vancomycin dose will be 50 mg/kg/day given orally 3 times per day for the 1st month and continue with the same dose for subsequent months if the clinical laboratory studies improved and are normal. If the laboratory studies are not normal the dose will be increased to 75 mg/kg/day given orally 3 times per day for the 2nd month and 100mg/kg/day given orally 3 times per day the 3rd month. If the laboratory studies do not improve by the end of the 3rd month since starting the vancomycin, the vancomycin will be stopped and the child will not continue the study.
Oral Vancomycin
|
Oral Vancomycin-Adults
n=8 Participants
For adults and children who weigh \>30 kg, the vancomycin dose will be 500 mg given orally 3 times per day for the 1st month and continue with this dose if the clinical laboratory studies improve and are normal. If the laboratory studies are not normal the dose will be increased to 750 mg 3 times per day for the 2nd month and 1000 mg 3 times per day the 3rd month.
Oral Vancomycin
|
|---|---|---|
|
Count of Participants With Abnormal Magnetic Resonance Cholangiopancreatography (MRCP) Imaging at Baseline and With Clinically Significant Improvement at Year 1
|
6 Participants
|
4 Participants
|
PRIMARY outcome
Timeframe: Baseline; Year 1Population: Participants with abnormal liver biopsy at baseline and who had a post-treatment liver biopsy are included in the analysis.
Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. Liver pathology was considered abnormal if the biopsy was S1 or greater on the liver fibrosis staging scale (S0 no fibrosis, S1 mild fibrosis, S2 moderate fibrosis, S3 sever fibrosis, S4 cirrhosis).
Outcome measures
| Measure |
Oral Vancomycin-Children
n=3 Participants
For children who weight \< or = 30 kg, the vancomycin dose will be 50 mg/kg/day given orally 3 times per day for the 1st month and continue with the same dose for subsequent months if the clinical laboratory studies improved and are normal. If the laboratory studies are not normal the dose will be increased to 75 mg/kg/day given orally 3 times per day for the 2nd month and 100mg/kg/day given orally 3 times per day the 3rd month. If the laboratory studies do not improve by the end of the 3rd month since starting the vancomycin, the vancomycin will be stopped and the child will not continue the study.
Oral Vancomycin
|
Oral Vancomycin-Adults
For adults and children who weigh \>30 kg, the vancomycin dose will be 500 mg given orally 3 times per day for the 1st month and continue with this dose if the clinical laboratory studies improve and are normal. If the laboratory studies are not normal the dose will be increased to 750 mg 3 times per day for the 2nd month and 1000 mg 3 times per day the 3rd month.
Oral Vancomycin
|
|---|---|---|
|
Count of Participants With Abnormal Liver Biopsies at Baseline and With Clinically Significant Improvement at Year 1
|
3 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline; Year 1Population: Participants with abnormal MRCP and/or liver biopsy at baseline are included in the analysis.
Clinically significant improvement was determined by investigator assessment per participant based on their medical history and disease stage. MRCP imaging was abnormal if it included biliary beading, biliary strictures, dilated bile duct, and/or liver fibrosis. Liver pathology was considered abnormal if the biopsy was S1 or greater on the liver fibrosis staging scale (S0 no fibrosis, S1 mild fibrosis, S2 moderate fibrosis, S3 sever fibrosis, S4 cirrhosis).
Outcome measures
| Measure |
Oral Vancomycin-Children
n=10 Participants
For children who weight \< or = 30 kg, the vancomycin dose will be 50 mg/kg/day given orally 3 times per day for the 1st month and continue with the same dose for subsequent months if the clinical laboratory studies improved and are normal. If the laboratory studies are not normal the dose will be increased to 75 mg/kg/day given orally 3 times per day for the 2nd month and 100mg/kg/day given orally 3 times per day the 3rd month. If the laboratory studies do not improve by the end of the 3rd month since starting the vancomycin, the vancomycin will be stopped and the child will not continue the study.
Oral Vancomycin
|
Oral Vancomycin-Adults
n=9 Participants
For adults and children who weigh \>30 kg, the vancomycin dose will be 500 mg given orally 3 times per day for the 1st month and continue with this dose if the clinical laboratory studies improve and are normal. If the laboratory studies are not normal the dose will be increased to 750 mg 3 times per day for the 2nd month and 1000 mg 3 times per day the 3rd month.
Oral Vancomycin
|
|---|---|---|
|
Count of Participants With Abnormal MRCP and/or Liver Biopsy at Baseline and With Clinically Significant Improvement at Year 1
|
10 Participants
|
4 Participants
|
Adverse Events
Oral Vancomycin-Children
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Oral Vancomycin-Adults
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Oral Vancomycin-Children
n=14 participants at risk
For children who weight \< or = 30 kg, the vancomycin dose will be 50 mg/kg/day given orally 3 times per day for the 1st month and continue with the same dose for subsequent months if the clinical laboratory studies improved and are normal. If the laboratory studies are not normal the dose will be increased to 75 mg/kg/day given orally 3 times per day for the 2nd month and 100mg/kg/day given orally 3 times per day the 3rd month. If the laboratory studies do not improve by the end of the 3rd month since starting the vancomycin, the vancomycin will be stopped and the child will not continue the study.
Oral Vancomycin
|
Oral Vancomycin-Adults
n=20 participants at risk
For adults and children who weigh \>30 kg, the vancomycin dose will be 500 mg given orally 3 times per day for the 1st month and continue with this dose if the clinical laboratory studies improve and are normal. If the laboratory studies are not normal the dose will be increased to 750 mg 3 times per day for the 2nd month and 1000 mg 3 times per day the 3rd month.
Oral Vancomycin
|
|---|---|---|
|
Hepatobiliary disorders
Biliary stricture requiring stent
|
7.1%
1/14 • Up to 2 years
|
0.00%
0/20 • Up to 2 years
|
|
Hepatobiliary disorders
Progression of PSC
|
7.1%
1/14 • Up to 2 years
|
0.00%
0/20 • Up to 2 years
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place