Trial Outcomes & Findings for N-Acetylcysteine in Biliary Atresia After Kasai Portoenterostomy (NCT NCT03499249)
NCT ID: NCT03499249
Last Updated: 2024-03-26
Results Overview
Expected is \~5% of participants based on historical controls (see protocol for summary of historical controls); a higher number is a better outcome
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
13 participants
Primary outcome timeframe
Within 24 weeks after KP
Results posted on
2024-03-26
Participant Flow
Participant milestones
| Measure |
N-Acetylcysteine Treatment
Will receive continuous intravenous NAC therapy (6.25 mg/kg/hour of 10 mg/ml solution, or 0.625 ml/kg/hour, to give 150 mg/kg/day), starting within 24 hours of completion of KP and lasting for a total of 7 days
N-Acetyl cysteine: Intravenous NAC therapy (6.25 mg/kg/hour of 10 mg/ml solution, or 0.625 ml/kg/hour, to give 150 mg/kg/day), starting within 24 hours of completion of KP and lasting for a total of 7 days
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|---|---|
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Overall Study
STARTED
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13
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Overall Study
COMPLETED
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12
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Overall Study
NOT COMPLETED
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1
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Reasons for withdrawal
| Measure |
N-Acetylcysteine Treatment
Will receive continuous intravenous NAC therapy (6.25 mg/kg/hour of 10 mg/ml solution, or 0.625 ml/kg/hour, to give 150 mg/kg/day), starting within 24 hours of completion of KP and lasting for a total of 7 days
N-Acetyl cysteine: Intravenous NAC therapy (6.25 mg/kg/hour of 10 mg/ml solution, or 0.625 ml/kg/hour, to give 150 mg/kg/day), starting within 24 hours of completion of KP and lasting for a total of 7 days
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|---|---|
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Overall Study
Physician Decision
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1
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Baseline Characteristics
N-Acetylcysteine in Biliary Atresia After Kasai Portoenterostomy
Baseline characteristics by cohort
| Measure |
N-Acetylcysteine Treatment
n=13 Participants
Will receive continuous intravenous NAC therapy (6.25 mg/kg/hour of 10 mg/ml solution, or 0.625 ml/kg/hour, to give 150 mg/kg/day), starting within 24 hours of completion of KP and lasting for a total of 7 days
N-Acetyl cysteine: Intravenous NAC therapy (6.25 mg/kg/hour of 10 mg/ml solution, or 0.625 ml/kg/hour, to give 150 mg/kg/day), starting within 24 hours of completion of KP and lasting for a total of 7 days
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|---|---|
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Age, Categorical
<=18 years
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13 Participants
n=5 Participants
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Age, Categorical
Between 18 and 65 years
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0 Participants
n=5 Participants
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Age, Categorical
>=65 years
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0 Participants
n=5 Participants
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Age, Continuous
|
36 days
STANDARD_DEVIATION 22 • n=5 Participants
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Sex: Female, Male
Female
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5 Participants
n=5 Participants
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Sex: Female, Male
Male
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8 Participants
n=5 Participants
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Race/Ethnicity, Customized
Hispanic, all races
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7 participants
n=5 Participants
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Race/Ethnicity, Customized
Non-Hispanic Asian
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1 participants
n=5 Participants
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Race/Ethnicity, Customized
Non-Hispanic Black
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3 participants
n=5 Participants
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Race/Ethnicity, Customized
non-Hispanic White
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2 participants
n=5 Participants
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Region of Enrollment
United States
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13 participants
n=5 Participants
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Aspartate aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-glutamyltransferase (GGT)
AST
|
123 IU/L
STANDARD_DEVIATION 83 • n=5 Participants
|
|
Aspartate aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-glutamyltransferase (GGT)
ALT
|
80 IU/L
STANDARD_DEVIATION 56 • n=5 Participants
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|
Aspartate aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-glutamyltransferase (GGT)
GGT
|
360 IU/L
STANDARD_DEVIATION 322 • n=5 Participants
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PRIMARY outcome
Timeframe: Within 24 weeks after KPExpected is \~5% of participants based on historical controls (see protocol for summary of historical controls); a higher number is a better outcome
Outcome measures
| Measure |
N-Acetylcysteine Treatment
n=12 Participants
Will receive continuous intravenous NAC therapy (6.25 mg/kg/hour of 10 mg/ml solution, or 0.625 ml/kg/hour, to give 150 mg/kg/day), starting within 24 hours of completion of KP and lasting for a total of 7 days
N-Acetyl cysteine: Intravenous NAC therapy (6.25 mg/kg/hour of 10 mg/ml solution, or 0.625 ml/kg/hour, to give 150 mg/kg/day), starting within 24 hours of completion of KP and lasting for a total of 7 days
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|---|---|
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Number of Patients With Biliary Atresia (BA) Achieving Total Serum Bile Acids Less Than or Equal to 10 *U*Mol/L Within 24 Weeks of Kasai Portoenterostomy (KP)
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0 Participants
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SECONDARY outcome
Timeframe: 3 days after KP compared to baseline (before KP); 7 days after KP compared to baseline (before KP)fold-change from baseline (ratio); a fold-change \<1 is a better outcome.
Outcome measures
| Measure |
N-Acetylcysteine Treatment
n=12 Participants
Will receive continuous intravenous NAC therapy (6.25 mg/kg/hour of 10 mg/ml solution, or 0.625 ml/kg/hour, to give 150 mg/kg/day), starting within 24 hours of completion of KP and lasting for a total of 7 days
N-Acetyl cysteine: Intravenous NAC therapy (6.25 mg/kg/hour of 10 mg/ml solution, or 0.625 ml/kg/hour, to give 150 mg/kg/day), starting within 24 hours of completion of KP and lasting for a total of 7 days
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|---|---|
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Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-glutamyltransferase (GGT) Fold, and Conjugated Bilirubin (Bc) Change Above Baseline at 3 Days and 7 Days After KP (During Treatment)
AST 3 days after KP
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1.5 fold change over baseline
Standard Deviation 0.5
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Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-glutamyltransferase (GGT) Fold, and Conjugated Bilirubin (Bc) Change Above Baseline at 3 Days and 7 Days After KP (During Treatment)
AST 7 days after KP
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1.4 fold change over baseline
Standard Deviation 0.4
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Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-glutamyltransferase (GGT) Fold, and Conjugated Bilirubin (Bc) Change Above Baseline at 3 Days and 7 Days After KP (During Treatment)
ALT 3 days after KP
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3.3 fold change over baseline
Standard Deviation 2.3
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Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-glutamyltransferase (GGT) Fold, and Conjugated Bilirubin (Bc) Change Above Baseline at 3 Days and 7 Days After KP (During Treatment)
ALT 7 days after KP
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2.1 fold change over baseline
Standard Deviation 0.5
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Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-glutamyltransferase (GGT) Fold, and Conjugated Bilirubin (Bc) Change Above Baseline at 3 Days and 7 Days After KP (During Treatment)
GGT 3 days after KP
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0.9 fold change over baseline
Standard Deviation 0.3
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Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-glutamyltransferase (GGT) Fold, and Conjugated Bilirubin (Bc) Change Above Baseline at 3 Days and 7 Days After KP (During Treatment)
GGT 7 days after KP
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1.7 fold change over baseline
Standard Deviation 0.9
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Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-glutamyltransferase (GGT) Fold, and Conjugated Bilirubin (Bc) Change Above Baseline at 3 Days and 7 Days After KP (During Treatment)
Bc 3 days after KP
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1.3 fold change over baseline
Standard Deviation 0.4
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Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-glutamyltransferase (GGT) Fold, and Conjugated Bilirubin (Bc) Change Above Baseline at 3 Days and 7 Days After KP (During Treatment)
Bc 7 days after KP
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1.3 fold change over baseline
Standard Deviation 0.4
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SECONDARY outcome
Timeframe: First two years of lifeEvents include Nasogastric (NG) feeds or Total Parental Nutrition (TPN) initiation, Splenomegaly (based on ultrasound findings), Thrombocytopenia (platelets \<150,000/mm3), Ascites (recorded when diuretics were needed for fluid accumulation), GI bleed (varices documented by endoscopy), Portal hypertension (one of the following: ascites, or combination of splenomegaly and thrombocytopenia), and Liver transplant or death; units are number of patients, higher numbers are worse outcomes.
Outcome measures
| Measure |
N-Acetylcysteine Treatment
n=12 Participants
Will receive continuous intravenous NAC therapy (6.25 mg/kg/hour of 10 mg/ml solution, or 0.625 ml/kg/hour, to give 150 mg/kg/day), starting within 24 hours of completion of KP and lasting for a total of 7 days
N-Acetyl cysteine: Intravenous NAC therapy (6.25 mg/kg/hour of 10 mg/ml solution, or 0.625 ml/kg/hour, to give 150 mg/kg/day), starting within 24 hours of completion of KP and lasting for a total of 7 days
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|---|---|
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Number of Patients Experiencing Sentinel Events in the First 2 Years of Life
NG feeds or TPN initiation
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4 Participants
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Number of Patients Experiencing Sentinel Events in the First 2 Years of Life
Splenomegaly
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7 Participants
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Number of Patients Experiencing Sentinel Events in the First 2 Years of Life
Thrombocytopenia
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5 Participants
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Number of Patients Experiencing Sentinel Events in the First 2 Years of Life
Ascites
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4 Participants
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Number of Patients Experiencing Sentinel Events in the First 2 Years of Life
GI bleed
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0 Participants
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Number of Patients Experiencing Sentinel Events in the First 2 Years of Life
Portal hypertension
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5 Participants
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Number of Patients Experiencing Sentinel Events in the First 2 Years of Life
Liver transplant or death
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4 Participants
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SECONDARY outcome
Timeframe: Within four weeks after KPUnits are number of patients, higher number is worse outcome
Outcome measures
| Measure |
N-Acetylcysteine Treatment
n=13 Participants
Will receive continuous intravenous NAC therapy (6.25 mg/kg/hour of 10 mg/ml solution, or 0.625 ml/kg/hour, to give 150 mg/kg/day), starting within 24 hours of completion of KP and lasting for a total of 7 days
N-Acetyl cysteine: Intravenous NAC therapy (6.25 mg/kg/hour of 10 mg/ml solution, or 0.625 ml/kg/hour, to give 150 mg/kg/day), starting within 24 hours of completion of KP and lasting for a total of 7 days
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|---|---|
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Number of Patients With Adverse Events Possibly Related to NAC, Including Rash, Urticaria, Pruritus, Tachycardia, Hypotension, Vomiting, Edema, Anaphylaxis, and Intravenous Line Issues
Tachycardia
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1 Participants
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Number of Patients With Adverse Events Possibly Related to NAC, Including Rash, Urticaria, Pruritus, Tachycardia, Hypotension, Vomiting, Edema, Anaphylaxis, and Intravenous Line Issues
Other
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0 Participants
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Adverse Events
N-Acetylcysteine Treatment
Serious events: 5 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
N-Acetylcysteine Treatment
n=13 participants at risk
Will receive continuous intravenous NAC therapy (6.25 mg/kg/hour of 10 mg/ml solution, or 0.625 ml/kg/hour, to give 150 mg/kg/day), starting within 24 hours of completion of KP and lasting for a total of 7 days
N-Acetyl cysteine: Intravenous NAC therapy (6.25 mg/kg/hour of 10 mg/ml solution, or 0.625 ml/kg/hour, to give 150 mg/kg/day), starting within 24 hours of completion of KP and lasting for a total of 7 days
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|---|---|
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Infections and infestations
Febrile illness
|
15.4%
2/13 • Number of events 2 • Within 28 days of KP (7 days of treatment and 21 days afterwards) for Serious adverse events, and Non-serious adverse events. Outcome measure. In first 2 years of life for All-Cause Mortality (this was also outcome measure #3).
Non-serious: Emesis with feeds, Loss of an intravenous (IV) line, Febrile illness, AST 400 IU/L \>pre-KP value, GGT 400 IU/L \>pre-KP value, Conjugated bilirubin 3 mg/dL \>pre-KP value, Total bilirubin 5 mg/dL \>pre-KP value Serious: Febrile illness, ALT 700 IU/L \>pre-KP value, INR \>2.0, Tachycardia
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Hepatobiliary disorders
ALT 700 IU/L >pre-KP value
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7.7%
1/13 • Number of events 1 • Within 28 days of KP (7 days of treatment and 21 days afterwards) for Serious adverse events, and Non-serious adverse events. Outcome measure. In first 2 years of life for All-Cause Mortality (this was also outcome measure #3).
Non-serious: Emesis with feeds, Loss of an intravenous (IV) line, Febrile illness, AST 400 IU/L \>pre-KP value, GGT 400 IU/L \>pre-KP value, Conjugated bilirubin 3 mg/dL \>pre-KP value, Total bilirubin 5 mg/dL \>pre-KP value Serious: Febrile illness, ALT 700 IU/L \>pre-KP value, INR \>2.0, Tachycardia
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Blood and lymphatic system disorders
INR >2.0
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7.7%
1/13 • Number of events 1 • Within 28 days of KP (7 days of treatment and 21 days afterwards) for Serious adverse events, and Non-serious adverse events. Outcome measure. In first 2 years of life for All-Cause Mortality (this was also outcome measure #3).
Non-serious: Emesis with feeds, Loss of an intravenous (IV) line, Febrile illness, AST 400 IU/L \>pre-KP value, GGT 400 IU/L \>pre-KP value, Conjugated bilirubin 3 mg/dL \>pre-KP value, Total bilirubin 5 mg/dL \>pre-KP value Serious: Febrile illness, ALT 700 IU/L \>pre-KP value, INR \>2.0, Tachycardia
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Cardiac disorders
Tachycardia
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7.7%
1/13 • Number of events 1 • Within 28 days of KP (7 days of treatment and 21 days afterwards) for Serious adverse events, and Non-serious adverse events. Outcome measure. In first 2 years of life for All-Cause Mortality (this was also outcome measure #3).
Non-serious: Emesis with feeds, Loss of an intravenous (IV) line, Febrile illness, AST 400 IU/L \>pre-KP value, GGT 400 IU/L \>pre-KP value, Conjugated bilirubin 3 mg/dL \>pre-KP value, Total bilirubin 5 mg/dL \>pre-KP value Serious: Febrile illness, ALT 700 IU/L \>pre-KP value, INR \>2.0, Tachycardia
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Other adverse events
| Measure |
N-Acetylcysteine Treatment
n=13 participants at risk
Will receive continuous intravenous NAC therapy (6.25 mg/kg/hour of 10 mg/ml solution, or 0.625 ml/kg/hour, to give 150 mg/kg/day), starting within 24 hours of completion of KP and lasting for a total of 7 days
N-Acetyl cysteine: Intravenous NAC therapy (6.25 mg/kg/hour of 10 mg/ml solution, or 0.625 ml/kg/hour, to give 150 mg/kg/day), starting within 24 hours of completion of KP and lasting for a total of 7 days
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|---|---|
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Gastrointestinal disorders
Emesis with feeds
|
23.1%
3/13 • Number of events 3 • Within 28 days of KP (7 days of treatment and 21 days afterwards) for Serious adverse events, and Non-serious adverse events. Outcome measure. In first 2 years of life for All-Cause Mortality (this was also outcome measure #3).
Non-serious: Emesis with feeds, Loss of an intravenous (IV) line, Febrile illness, AST 400 IU/L \>pre-KP value, GGT 400 IU/L \>pre-KP value, Conjugated bilirubin 3 mg/dL \>pre-KP value, Total bilirubin 5 mg/dL \>pre-KP value Serious: Febrile illness, ALT 700 IU/L \>pre-KP value, INR \>2.0, Tachycardia
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Investigations
Loss of an IV
|
30.8%
4/13 • Number of events 4 • Within 28 days of KP (7 days of treatment and 21 days afterwards) for Serious adverse events, and Non-serious adverse events. Outcome measure. In first 2 years of life for All-Cause Mortality (this was also outcome measure #3).
Non-serious: Emesis with feeds, Loss of an intravenous (IV) line, Febrile illness, AST 400 IU/L \>pre-KP value, GGT 400 IU/L \>pre-KP value, Conjugated bilirubin 3 mg/dL \>pre-KP value, Total bilirubin 5 mg/dL \>pre-KP value Serious: Febrile illness, ALT 700 IU/L \>pre-KP value, INR \>2.0, Tachycardia
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|
Infections and infestations
Febrile illness
|
7.7%
1/13 • Number of events 1 • Within 28 days of KP (7 days of treatment and 21 days afterwards) for Serious adverse events, and Non-serious adverse events. Outcome measure. In first 2 years of life for All-Cause Mortality (this was also outcome measure #3).
Non-serious: Emesis with feeds, Loss of an intravenous (IV) line, Febrile illness, AST 400 IU/L \>pre-KP value, GGT 400 IU/L \>pre-KP value, Conjugated bilirubin 3 mg/dL \>pre-KP value, Total bilirubin 5 mg/dL \>pre-KP value Serious: Febrile illness, ALT 700 IU/L \>pre-KP value, INR \>2.0, Tachycardia
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|
Hepatobiliary disorders
AST 400 IU/L >pre-KP value
|
46.2%
6/13 • Number of events 6 • Within 28 days of KP (7 days of treatment and 21 days afterwards) for Serious adverse events, and Non-serious adverse events. Outcome measure. In first 2 years of life for All-Cause Mortality (this was also outcome measure #3).
Non-serious: Emesis with feeds, Loss of an intravenous (IV) line, Febrile illness, AST 400 IU/L \>pre-KP value, GGT 400 IU/L \>pre-KP value, Conjugated bilirubin 3 mg/dL \>pre-KP value, Total bilirubin 5 mg/dL \>pre-KP value Serious: Febrile illness, ALT 700 IU/L \>pre-KP value, INR \>2.0, Tachycardia
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|
Hepatobiliary disorders
GGT 400 IU/L >pre-KP value
|
61.5%
8/13 • Number of events 8 • Within 28 days of KP (7 days of treatment and 21 days afterwards) for Serious adverse events, and Non-serious adverse events. Outcome measure. In first 2 years of life for All-Cause Mortality (this was also outcome measure #3).
Non-serious: Emesis with feeds, Loss of an intravenous (IV) line, Febrile illness, AST 400 IU/L \>pre-KP value, GGT 400 IU/L \>pre-KP value, Conjugated bilirubin 3 mg/dL \>pre-KP value, Total bilirubin 5 mg/dL \>pre-KP value Serious: Febrile illness, ALT 700 IU/L \>pre-KP value, INR \>2.0, Tachycardia
|
|
Hepatobiliary disorders
Conjugated bilirubin 3 mg/dL >pre-KP value
|
15.4%
2/13 • Number of events 2 • Within 28 days of KP (7 days of treatment and 21 days afterwards) for Serious adverse events, and Non-serious adverse events. Outcome measure. In first 2 years of life for All-Cause Mortality (this was also outcome measure #3).
Non-serious: Emesis with feeds, Loss of an intravenous (IV) line, Febrile illness, AST 400 IU/L \>pre-KP value, GGT 400 IU/L \>pre-KP value, Conjugated bilirubin 3 mg/dL \>pre-KP value, Total bilirubin 5 mg/dL \>pre-KP value Serious: Febrile illness, ALT 700 IU/L \>pre-KP value, INR \>2.0, Tachycardia
|
|
Hepatobiliary disorders
Total bilirubin 5 mg/dL >pre-KP value
|
7.7%
1/13 • Number of events 1 • Within 28 days of KP (7 days of treatment and 21 days afterwards) for Serious adverse events, and Non-serious adverse events. Outcome measure. In first 2 years of life for All-Cause Mortality (this was also outcome measure #3).
Non-serious: Emesis with feeds, Loss of an intravenous (IV) line, Febrile illness, AST 400 IU/L \>pre-KP value, GGT 400 IU/L \>pre-KP value, Conjugated bilirubin 3 mg/dL \>pre-KP value, Total bilirubin 5 mg/dL \>pre-KP value Serious: Febrile illness, ALT 700 IU/L \>pre-KP value, INR \>2.0, Tachycardia
|
Additional Information
Sanjiv Harpavat
Baylor College of Medicine and Texas Children's Hospital
Phone: 832-824-2099
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place