Trial Outcomes & Findings for Liver Fibrosis in Patients Transplanted for Hepatitis C Receiving Either Cyclosporine Microemulsion or Tacrolimus (NCT NCT00260208)
NCT ID: NCT00260208
Last Updated: 2011-12-06
Results Overview
Assessment of hepatic fibrosis was performed with liver biopsies at Day 1, Month 6, 12 and 24, read centrally by two independent pathologists blinded to treatment arm and time of biopsy. Ishak-Knodell score was used to stage liver disease; 0= None; 1= Portal fibrosis (some); 2= Portal fibrosis (most); 3= Bridging fibrosis (few); 4= Bridging fibrosis (many); 5 = Incomplete cirrhosis; 6 = Cirrhosis. Higher score indicates greater fibrosis. Logistic regression on the presence of IK\>=2 was applied based on central biopsy readings only.
Recruitment status
TERMINATED
Study phase
PHASE4
Target enrollment
361 participants
Primary outcome timeframe
1 year post-transplant
Results posted on
2011-12-06
Participant Flow
361 patients were randomized, 185 to the cyclosporin A arm and 176 to tacrolimus. Five patients (1 cyclosporine A, 4 tacrolimus) did not receive any dose of study medication and were therefore excluded from the safety population.
Participant milestones
| Measure |
Cyclosporin A
The first administration of Cyclosporin A (CsA) was within the first 24 hours post-transplantation at an initial dose of 10-15mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally, via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the study, it was recommended that the dose of CsA was adjusted, as necessary, to achieve and maintain the C2 or C0 blood CsA concentration within the target ranges.
|
Tacrolimus
Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.
|
|---|---|---|
|
Overall Study
STARTED
|
184
|
172
|
|
Overall Study
Intent to Treat (ITT) Population
|
182
|
169
|
|
Overall Study
Modified ITT
|
101
|
96
|
|
Overall Study
COMPLETED
|
137
|
138
|
|
Overall Study
NOT COMPLETED
|
47
|
34
|
Reasons for withdrawal
| Measure |
Cyclosporin A
The first administration of Cyclosporin A (CsA) was within the first 24 hours post-transplantation at an initial dose of 10-15mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally, via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the study, it was recommended that the dose of CsA was adjusted, as necessary, to achieve and maintain the C2 or C0 blood CsA concentration within the target ranges.
|
Tacrolimus
Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.
|
|---|---|---|
|
Overall Study
Subject withdrew consent
|
11
|
7
|
|
Overall Study
Lost to Follow-up
|
6
|
1
|
|
Overall Study
Death
|
12
|
10
|
|
Overall Study
Missing
|
18
|
16
|
Baseline Characteristics
Liver Fibrosis in Patients Transplanted for Hepatitis C Receiving Either Cyclosporine Microemulsion or Tacrolimus
Baseline characteristics by cohort
| Measure |
Cyclosporin A
n=182 Participants
The first administration of Cyclosporin A (CsA) was within the first 24 hours post-transplantation at an initial dose of 10-15mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally, via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the study, it was recommended that the dose of CsA was adjusted, as necessary, to achieve and maintain the C2 or C0 blood CsA concentration within the target ranges.
|
Tacrolimus
n=169 Participants
Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.
|
Total
n=351 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
54.4 years
STANDARD_DEVIATION 6.9 • n=93 Participants
|
54.4 years
STANDARD_DEVIATION 7.1 • n=4 Participants
|
54.4 years
STANDARD_DEVIATION 7.0 • n=27 Participants
|
|
Age, Customized
< 65 years
|
163 Participants
n=93 Participants
|
154 Participants
n=4 Participants
|
317 Participants
n=27 Participants
|
|
Age, Customized
≥ 65 years
|
19 Participants
n=93 Participants
|
15 Participants
n=4 Participants
|
34 Participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
57 Participants
n=93 Participants
|
48 Participants
n=4 Participants
|
105 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
125 Participants
n=93 Participants
|
121 Participants
n=4 Participants
|
246 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 1 year post-transplantPopulation: The modified intent-to-treat population (mITT) included patients treated with study drug at least up to 30 days before Month 12 visit and a liver biopsy had to be performed at this visit. Also included were patients with an earlier biopsy that showed an Ishak-Knodell fibrosis score ≥2 and treated at least up to 30 days before that biopsy was taken.
Assessment of hepatic fibrosis was performed with liver biopsies at Day 1, Month 6, 12 and 24, read centrally by two independent pathologists blinded to treatment arm and time of biopsy. Ishak-Knodell score was used to stage liver disease; 0= None; 1= Portal fibrosis (some); 2= Portal fibrosis (most); 3= Bridging fibrosis (few); 4= Bridging fibrosis (many); 5 = Incomplete cirrhosis; 6 = Cirrhosis. Higher score indicates greater fibrosis. Logistic regression on the presence of IK\>=2 was applied based on central biopsy readings only.
Outcome measures
| Measure |
Cyclosporin A
n=88 Participants
The first administration of Cyclosporin A (CsA) was within the first 24 hours post-transplantation at an initial dose of 10-15mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally, via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the study, it was recommended that the dose of CsA was adjusted, as necessary, to achieve and maintain the C2 or C0 blood CsA concentration within the target ranges.
|
Tacrolimus
n=77 Participants
Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.
|
|---|---|---|
|
Number of Participants With Fibrosis Score 2 or Above [Ishak-Knodell Fibrosis Score (FS) ≥ 2] Within 1 Year Post-transplant
|
63 Participants
|
52 Participants
|
SECONDARY outcome
Timeframe: 1 year post-transplantPopulation: Intent-to-treat (ITT) population: all patients as randomized that were transplanted, received at least one dose of study drug and had at least one post-baseline efficacy assessment.
The number of participants with combined end point of death or graft loss or presented with a Ishak-Knodell fibrosis score (FS) ≥2 was calculated. Graft loss was considered to have occurred when allograft was presumed to be lost if a patient had liver retransplant or died. Assessment of hepatic fibrosis was performed with liver biopsies read centrally. Ishak-Knodell FS was used to stage liver disease; 0=none; 1=portal fibrosis (some); 2=portal fibrosis (most); 3=bridging fibrosis (few); 4=bridging fibrosis (many); 5=Incomplete cirrhosis; 6=cirrhosis. Higher score indicates greater fibrosis.
Outcome measures
| Measure |
Cyclosporin A
n=182 Participants
The first administration of Cyclosporin A (CsA) was within the first 24 hours post-transplantation at an initial dose of 10-15mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally, via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the study, it was recommended that the dose of CsA was adjusted, as necessary, to achieve and maintain the C2 or C0 blood CsA concentration within the target ranges.
|
Tacrolimus
n=169 Participants
Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.
|
|---|---|---|
|
Number of Participants With Combined Endpoint of Death or Graft Loss or Fibrosis Score (FS) ≥ 2
|
77 Participants
|
71 Participants
|
SECONDARY outcome
Timeframe: 1 year post-transplantationPopulation: Intent-to-treat population: all patients as randomized that were transplanted, received at least one dose of study drug and had at least one post-baseline efficacy assessment.
Fibrosing cholestatic hepatitis (FCH) is characterized by progressive jaundice with a rapid decline in liver function leading to liver failure, most often associated with markedly elevated viral levels detected in the bloodstream (e.g. more than 20 times pre-liver transplantation levels) and in the liver tissue as well. The presence of FCH was reported based on the diagnosis given by the investigator.
Outcome measures
| Measure |
Cyclosporin A
n=182 Participants
The first administration of Cyclosporin A (CsA) was within the first 24 hours post-transplantation at an initial dose of 10-15mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally, via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the study, it was recommended that the dose of CsA was adjusted, as necessary, to achieve and maintain the C2 or C0 blood CsA concentration within the target ranges.
|
Tacrolimus
n=169 Participants
Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.
|
|---|---|---|
|
Number of Participants With Fibrosing Cholestatic Hepatitis
|
9 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: 1 year post-transplantPopulation: Intent-to-treat (ITT) population: all patients as randomized that were transplanted, received at least one dose of study drug and had at least one post-baseline efficacy assessment.
Graft loss was considered to have occurred when allograft was presumed to be lost if a patient had a liver re-transplant or died.
Outcome measures
| Measure |
Cyclosporin A
n=182 Participants
The first administration of Cyclosporin A (CsA) was within the first 24 hours post-transplantation at an initial dose of 10-15mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally, via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the study, it was recommended that the dose of CsA was adjusted, as necessary, to achieve and maintain the C2 or C0 blood CsA concentration within the target ranges.
|
Tacrolimus
n=169 Participants
Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.
|
|---|---|---|
|
Number of Participants With Death, Graft Loss, Death or Graft Loss, Graft Loss With Re-transplantation
Death
|
15 Participants
|
15 Participants
|
|
Number of Participants With Death, Graft Loss, Death or Graft Loss, Graft Loss With Re-transplantation
Graft loss
|
8 Participants
|
13 Participants
|
|
Number of Participants With Death, Graft Loss, Death or Graft Loss, Graft Loss With Re-transplantation
Death or Graft loss
|
19 Participants
|
23 Participants
|
|
Number of Participants With Death, Graft Loss, Death or Graft Loss, Graft Loss With Re-transplantation
Graft loss with re-transplantation
|
3 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: 1 year post-transplantPopulation: Intent-to-treat (ITT) population: all patients as randomized that were transplanted, received at least one dose of study drug and had at least one post-baseline efficacy assessment.
Treated acute rejection is defined as an acute rejection, clinically suspected, whether biopsy-proven or not, which has been treated and confirmed by the investigator according to the response to therapy. BPAR was defined as a treated acute rejection confirmed by biopsy. The local pathologist graded biopsies according to the Banff (1997) criteria. A sub-clinical rejection was defined as a rejection identified by center driven biopsy, i.e. a biopsy performed routinely at some pre-defined time points after transplantation as per center practice in the absence of any clinical signs of rejection.
Outcome measures
| Measure |
Cyclosporin A
n=182 Participants
The first administration of Cyclosporin A (CsA) was within the first 24 hours post-transplantation at an initial dose of 10-15mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally, via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the study, it was recommended that the dose of CsA was adjusted, as necessary, to achieve and maintain the C2 or C0 blood CsA concentration within the target ranges.
|
Tacrolimus
n=169 Participants
Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.
|
|---|---|---|
|
Number of Participants With Treated Acute Rejection, Biopsy Proven Acute Rejection (BPAR), and Sub-clinical Rejection
Treated acute rejection
|
28 Participants
|
22 Participants
|
|
Number of Participants With Treated Acute Rejection, Biopsy Proven Acute Rejection (BPAR), and Sub-clinical Rejection
Biopsy prove acute rejection (BPAR)
|
28 Participants
|
19 Participants
|
|
Number of Participants With Treated Acute Rejection, Biopsy Proven Acute Rejection (BPAR), and Sub-clinical Rejection
Sub-clinical rejection
|
4 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: 1 year post-transplantPopulation: Intent-to-treat (ITT) population: all patients as randomized that were transplanted, received at least one dose of study drug and had at least one post-baseline efficacy assessment.
BPAR was defined as a treated acute rejection confirmed by biopsy. The local pathologist graded biopsies according to the Banff (1997) criteria. Graft loss was considered to have occurred when allograft was presumed to be lost if a patient had a liver re-transplant or died.
Outcome measures
| Measure |
Cyclosporin A
n=182 Participants
The first administration of Cyclosporin A (CsA) was within the first 24 hours post-transplantation at an initial dose of 10-15mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally, via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the study, it was recommended that the dose of CsA was adjusted, as necessary, to achieve and maintain the C2 or C0 blood CsA concentration within the target ranges.
|
Tacrolimus
n=169 Participants
Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.
|
|---|---|---|
|
Number of Participants With Combined Endpoint of Death or Graft Loss or Biopsy Proven Acute Rejection (BPAR)
|
45 Participants
|
42 Participants
|
SECONDARY outcome
Timeframe: 1 year post-transplantPopulation: Intent-to-treat (ITT) population: all patients as randomized that were transplanted, received at least one dose of study drug and had at least one post-baseline efficacy assessment.
Cirrhosis was resulted due to the recurrence of the hepatitis C virus infection in the transplanted liver.
Outcome measures
| Measure |
Cyclosporin A
n=182 Participants
The first administration of Cyclosporin A (CsA) was within the first 24 hours post-transplantation at an initial dose of 10-15mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally, via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the study, it was recommended that the dose of CsA was adjusted, as necessary, to achieve and maintain the C2 or C0 blood CsA concentration within the target ranges.
|
Tacrolimus
n=169 Participants
Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.
|
|---|---|---|
|
Number of Participants With Death or Re-transplantation Due to Recurrence of Hepatitis C Cirrhosis
|
16 Participants
|
17 Participants
|
SECONDARY outcome
Timeframe: 1 year post-transplantPopulation: The Intent-To-Treat (ITT) population consisted of all patients as randomized that were transplanted, received at least one dose of study drug and had at least one post-baseline efficacy assessment.
Assessment of hepatic fibrosis was performed with liver biopsies at Day 1, Month 6, 12 and 24, read centrally by two independent pathologists blinded to treatment arm and time of biopsy. Ishak-Knodell score was used to stage liver disease; 0= None; 1= Portal fibrosis (some); 2= Portal fibrosis (most); 3= Bridging fibrosis (few); 4= Bridging fibrosis (many); 5 = Incomplete cirrhosis; 6 = Cirrhosis. Higher score indicates greater fibrosis.
Outcome measures
| Measure |
Cyclosporin A
n=182 Participants
The first administration of Cyclosporin A (CsA) was within the first 24 hours post-transplantation at an initial dose of 10-15mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally, via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the study, it was recommended that the dose of CsA was adjusted, as necessary, to achieve and maintain the C2 or C0 blood CsA concentration within the target ranges.
|
Tacrolimus
n=169 Participants
Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.
|
|---|---|---|
|
Number of Participants With Fibrosis Score 2 or Above [Ishak-Knodell Fibrosis Score (FS) ≥ 2] Within 1 Year Post-transplant (Intent to Treat Population)
|
63 Participants
|
54 Participants
|
SECONDARY outcome
Timeframe: 1 year post-transplantPopulation: Intent-to-treat (ITT) population: all patients as randomized that were transplanted, received at least one dose of study drug and had at least one post-baseline efficacy assessment. "n" is number participants with assessable data in each category.
The mean value (in Units per liter, IU/L) of following tests were calculated at 1 year post-transplant: * Serum glutamic pyruvic transaminase (SGPT) * Serum Glutamic Oxaloacetic Transaminase (SGOT) * Bilirubin * Alkaline Phosphate * γ-Glutamyltransferase (GGT)
Outcome measures
| Measure |
Cyclosporin A
n=112 Participants
The first administration of Cyclosporin A (CsA) was within the first 24 hours post-transplantation at an initial dose of 10-15mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally, via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the study, it was recommended that the dose of CsA was adjusted, as necessary, to achieve and maintain the C2 or C0 blood CsA concentration within the target ranges.
|
Tacrolimus
n=115 Participants
Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.
|
|---|---|---|
|
Mean Value of Liver Function Tests at 1 Year Post-transplantation
Bilirubin (n= 111, 115)
|
40.3 IU/L
Standard Deviation 85.5
|
19.3 IU/L
Standard Deviation 27.9
|
|
Mean Value of Liver Function Tests at 1 Year Post-transplantation
SGPT (n= 112, 112)
|
100.5 IU/L
Standard Deviation 178.8
|
81.7 IU/L
Standard Deviation 82.5
|
|
Mean Value of Liver Function Tests at 1 Year Post-transplantation
SGOT (n= 112,112)
|
92.0 IU/L
Standard Deviation 122.3
|
72.8 IU/L
Standard Deviation 98.2
|
|
Mean Value of Liver Function Tests at 1 Year Post-transplantation
Alkaline Phosphate (n= 111, 115)
|
174.7 IU/L
Standard Deviation 152.9
|
152.9 IU/L
Standard Deviation 127.3
|
|
Mean Value of Liver Function Tests at 1 Year Post-transplantation
GGT (n= 103, 110)
|
182.2 IU/L
Standard Deviation 224.3
|
168.5 IU/L
Standard Deviation 278.7
|
SECONDARY outcome
Timeframe: Pre-transplant (Day 1), Day , Day 8, Day 29, Month 6 and 12 post- transplantPopulation: Intent-to-treat (ITT) population: all patients as randomized that were transplanted, received at least one dose of study drug and had at least one post-baseline efficacy assessment. "n" in each of the categories is the number of participants with data at the given time point.
HCV RNA was measured (IU/µL)centrally pre-transplant (Day 1) and at 48 hours (Day 3), Day 8 and 29, Month 6 and 12 post-transplant and concomitantly to any additional biopsies performed.
Outcome measures
| Measure |
Cyclosporin A
n=182 Participants
The first administration of Cyclosporin A (CsA) was within the first 24 hours post-transplantation at an initial dose of 10-15mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally, via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the study, it was recommended that the dose of CsA was adjusted, as necessary, to achieve and maintain the C2 or C0 blood CsA concentration within the target ranges.
|
Tacrolimus
n=169 Participants
Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.
|
|---|---|---|
|
Log-transformed Hepatitis C Virus Ribonucleic Acid (HCV RNA) Values up to 1 Year Post Transplant
Day 1 (n=116, 111)
|
0.71 IU/µL
Standard Deviation 0.887
|
0.62 IU/µL
Standard Deviation 0.809
|
|
Log-transformed Hepatitis C Virus Ribonucleic Acid (HCV RNA) Values up to 1 Year Post Transplant
Day 3 (n= 136, 120)
|
0.98 IU/µL
Standard Deviation 1.112
|
0.91 IU/µL
Standard Deviation 1.024
|
|
Log-transformed Hepatitis C Virus Ribonucleic Acid (HCV RNA) Values up to 1 Year Post Transplant
Day 8 (n= 122, 117)
|
1.58 IU/µL
Standard Deviation 1.569
|
1.45 IU/µL
Standard Deviation 1.557
|
|
Log-transformed Hepatitis C Virus Ribonucleic Acid (HCV RNA) Values up to 1 Year Post Transplant
Day 29 (n=128, 109)
|
2.56 IU/µL
Standard Deviation 1.658
|
2.74 IU/µL
Standard Deviation 1.439
|
|
Log-transformed Hepatitis C Virus Ribonucleic Acid (HCV RNA) Values up to 1 Year Post Transplant
Month 6 (n=96, 98)
|
3.45 IU/µL
Standard Deviation 1.069
|
3.14 IU/µL
Standard Deviation 1.332
|
|
Log-transformed Hepatitis C Virus Ribonucleic Acid (HCV RNA) Values up to 1 Year Post Transplant
Month 12 (n= 85, 88)
|
3.17 IU/µL
Standard Deviation 1.246
|
3.13 IU/µL
Standard Deviation 1.385
|
SECONDARY outcome
Timeframe: Between 1 and 2 yearsPopulation: The outcome measure was not analyzed because of premature termination of study.
Assessment of hepatic fibrosis was performed with liver biopsies at Day 1, Month 6, 12 and 24, read centrally by two independent pathologists blinded to treatment arm and time of biopsy. Ishak-Knodell score was used to stage liver disease; 0= None; 1= Portal fibrosis (some); 2= Portal fibrosis (most); 3= Bridging fibrosis (few); 4= Bridging fibrosis (many); 5 = Incomplete cirrhosis; 6 = Cirrhosis. Higher score indicates greater fibrosis. An increase of at least 1 stage demonstrated a worsening of the disease, i.e. the transition from one score to the next higher one.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At 1and 2 years and its evolution over timePopulation: This outcome was not analyzed because of premature termination of study.
Assessment of hepatic fibrosis was performed with liver biopsies at Day 1, Month 6, 12 and 24, read centrally by two independent pathologists blinded to treatment arm and time of biopsy. Ishak-Knodell score was used to stage liver disease; 0= None; 1= Portal fibrosis (some); 2= Portal fibrosis (most); 3= Bridging fibrosis (few); 4= Bridging fibrosis (many); 5 = Incomplete cirrhosis; 6 = Cirrhosis. Higher score indicates greater fibrosis. The mean score was equivalent to mean of IK at 1 and 2 years (evolution over time).
Outcome measures
Outcome data not reported
Adverse Events
Cyclosporin A
Serious events: 148 serious events
Other events: 182 other events
Deaths: 0 deaths
Tacrolimus
Serious events: 138 serious events
Other events: 167 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cyclosporin A
n=184 participants at risk
The first administration of Cyclosporin A (CsA) was within the first 24 hours post-transplantation at an initial dose of 10-15mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally, via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the study, it was recommended that the dose of CsA was adjusted, as necessary, to achieve and maintain the C2 or C0 blood CsA concentration within the target ranges.
|
Tacrolimus
n=172 participants at risk
Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.54%
1/184
|
0.58%
1/172
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/184
|
0.58%
1/172
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.54%
1/184
|
0.58%
1/172
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.54%
1/184
|
0.00%
0/172
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/184
|
1.2%
2/172
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.1%
2/184
|
0.00%
0/172
|
|
Cardiac disorders
Atrial tachycardia
|
0.54%
1/184
|
0.00%
0/172
|
|
Cardiac disorders
Cardiac arrest
|
0.54%
1/184
|
1.2%
2/172
|
|
Cardiac disorders
Cardiac disorder
|
0.54%
1/184
|
0.00%
0/172
|
|
Cardiac disorders
Cardiac failure
|
0.54%
1/184
|
0.00%
0/172
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.54%
1/184
|
0.00%
0/172
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.00%
0/184
|
0.58%
1/172
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/184
|
0.58%
1/172
|
|
Cardiac disorders
Pericardial effusion
|
0.54%
1/184
|
0.00%
0/172
|
|
Cardiac disorders
Ventricular tachycardia
|
0.54%
1/184
|
0.00%
0/172
|
|
Gastrointestinal disorders
Abdominal adhesions
|
0.54%
1/184
|
0.00%
0/172
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/184
|
0.58%
1/172
|
|
Gastrointestinal disorders
Abdominal pain
|
1.6%
3/184
|
5.2%
9/172
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.54%
1/184
|
1.2%
2/172
|
|
Gastrointestinal disorders
Abdominal rigidity
|
0.54%
1/184
|
0.00%
0/172
|
|
Gastrointestinal disorders
Ascites
|
1.1%
2/184
|
1.2%
2/172
|
|
Gastrointestinal disorders
Colitis
|
0.54%
1/184
|
0.00%
0/172
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/184
|
0.58%
1/172
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/184
|
1.2%
2/172
|
|
Gastrointestinal disorders
Duodenitis
|
0.00%
0/184
|
0.58%
1/172
|
|
Gastrointestinal disorders
Dysphagia
|
0.54%
1/184
|
0.00%
0/172
|
|
Gastrointestinal disorders
Epigastric discomfort
|
0.54%
1/184
|
0.00%
0/172
|
|
Gastrointestinal disorders
Faeces pale
|
0.00%
0/184
|
0.58%
1/172
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.54%
1/184
|
0.58%
1/172
|
|
Gastrointestinal disorders
Ileus
|
0.54%
1/184
|
1.2%
2/172
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.54%
1/184
|
1.2%
2/172
|
|
Gastrointestinal disorders
Inguinal hernia, obstructive
|
0.54%
1/184
|
0.00%
0/172
|
|
Gastrointestinal disorders
Intestinal strangulation
|
0.54%
1/184
|
0.00%
0/172
|
|
Gastrointestinal disorders
Localised intraabdominal fluid collection
|
0.00%
0/184
|
2.3%
4/172
|
|
Gastrointestinal disorders
Mechanical ileus
|
0.54%
1/184
|
0.00%
0/172
|
|
Gastrointestinal disorders
Melaena
|
0.54%
1/184
|
0.00%
0/172
|
|
Gastrointestinal disorders
Nausea
|
1.6%
3/184
|
0.58%
1/172
|
|
Gastrointestinal disorders
Pancreatitis
|
0.54%
1/184
|
0.58%
1/172
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.54%
1/184
|
0.00%
0/172
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.54%
1/184
|
0.00%
0/172
|
|
Gastrointestinal disorders
Vomiting
|
3.3%
6/184
|
1.2%
2/172
|
|
General disorders
Asthenia
|
0.54%
1/184
|
0.00%
0/172
|
|
General disorders
Chest pain
|
0.00%
0/184
|
0.58%
1/172
|
|
General disorders
Effusion
|
0.54%
1/184
|
0.00%
0/172
|
|
General disorders
General physical health deterioration
|
0.00%
0/184
|
1.2%
2/172
|
|
General disorders
Hernia
|
0.54%
1/184
|
0.00%
0/172
|
|
General disorders
Hernia obstructive
|
0.54%
1/184
|
0.58%
1/172
|
|
General disorders
Hernia pain
|
0.00%
0/184
|
0.58%
1/172
|
|
General disorders
Impaired healing
|
1.1%
2/184
|
0.00%
0/172
|
|
General disorders
Multi-organ failure
|
1.1%
2/184
|
0.00%
0/172
|
|
General disorders
Non-cardiac chest pain
|
0.54%
1/184
|
0.58%
1/172
|
|
General disorders
Oedema peripheral
|
0.00%
0/184
|
0.58%
1/172
|
|
General disorders
Pain
|
0.00%
0/184
|
0.58%
1/172
|
|
General disorders
Pyrexia
|
7.1%
13/184
|
5.2%
9/172
|
|
Hepatobiliary disorders
Acute hepatic failure
|
0.00%
0/184
|
0.58%
1/172
|
|
Hepatobiliary disorders
Bile duct necrosis
|
0.54%
1/184
|
0.58%
1/172
|
|
Hepatobiliary disorders
Bile duct obstruction
|
0.54%
1/184
|
1.7%
3/172
|
|
Hepatobiliary disorders
Bile duct stenosis
|
4.3%
8/184
|
1.7%
3/172
|
|
Hepatobiliary disorders
Bile duct stone
|
0.54%
1/184
|
0.00%
0/172
|
|
Hepatobiliary disorders
Biliary cirrhosis
|
0.54%
1/184
|
0.00%
0/172
|
|
Hepatobiliary disorders
Biliary ischaemia
|
0.00%
0/184
|
0.58%
1/172
|
|
Hepatobiliary disorders
Biloma
|
0.54%
1/184
|
1.2%
2/172
|
|
Hepatobiliary disorders
Cholangitis
|
4.9%
9/184
|
1.2%
2/172
|
|
Hepatobiliary disorders
Cholestasis
|
0.54%
1/184
|
0.58%
1/172
|
|
Hepatobiliary disorders
Haemobilia
|
0.00%
0/184
|
0.58%
1/172
|
|
Hepatobiliary disorders
Hepatic artery stenosis
|
1.1%
2/184
|
1.2%
2/172
|
|
Hepatobiliary disorders
Hepatic artery thrombosis
|
0.54%
1/184
|
1.7%
3/172
|
|
Hepatobiliary disorders
Hepatic failure
|
2.7%
5/184
|
0.58%
1/172
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
1.1%
2/184
|
1.7%
3/172
|
|
Hepatobiliary disorders
Hepatic haemorrhage
|
0.00%
0/184
|
0.58%
1/172
|
|
Hepatobiliary disorders
Hepatic infiltration eosinophilic
|
0.00%
0/184
|
0.58%
1/172
|
|
Hepatobiliary disorders
Hepatic vein thrombosis
|
0.00%
0/184
|
0.58%
1/172
|
|
Hepatobiliary disorders
Hepatitis
|
0.54%
1/184
|
0.00%
0/172
|
|
Hepatobiliary disorders
Hepatitis cholestatic
|
0.00%
0/184
|
0.58%
1/172
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.54%
1/184
|
0.00%
0/172
|
|
Hepatobiliary disorders
Hypertransaminasaemia
|
0.54%
1/184
|
0.00%
0/172
|
|
Hepatobiliary disorders
Ischaemic hepatitis
|
0.54%
1/184
|
0.00%
0/172
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
0.00%
0/184
|
0.58%
1/172
|
|
Immune system disorders
Drug hypersensitivity
|
0.54%
1/184
|
0.00%
0/172
|
|
Immune system disorders
Liver transplant rejection
|
6.0%
11/184
|
4.1%
7/172
|
|
Immune system disorders
Transplant rejection
|
1.1%
2/184
|
1.2%
2/172
|
|
Infections and infestations
Abdominal abscess
|
0.54%
1/184
|
1.2%
2/172
|
|
Infections and infestations
Abdominal sepsis
|
0.00%
0/184
|
0.58%
1/172
|
|
Infections and infestations
Abdominal wall abscess
|
0.00%
0/184
|
0.58%
1/172
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/184
|
0.58%
1/172
|
|
Infections and infestations
Bone abscess
|
0.00%
0/184
|
0.58%
1/172
|
|
Infections and infestations
Bronchitis
|
0.00%
0/184
|
0.58%
1/172
|
|
Infections and infestations
Bronchopneumonia
|
0.54%
1/184
|
0.00%
0/172
|
|
Infections and infestations
Cellulitis
|
1.1%
2/184
|
0.58%
1/172
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/184
|
0.58%
1/172
|
|
Infections and infestations
Cytomegalovirus hepatitis
|
0.00%
0/184
|
1.2%
2/172
|
|
Infections and infestations
Cytomegalovirus infection
|
3.8%
7/184
|
0.58%
1/172
|
|
Infections and infestations
Cytomegalovirus viraemia
|
0.54%
1/184
|
0.00%
0/172
|
|
Infections and infestations
Enterobacter infection
|
0.54%
1/184
|
0.00%
0/172
|
|
Infections and infestations
Enterocolitis infectious
|
0.54%
1/184
|
0.00%
0/172
|
|
Infections and infestations
Escherichia sepsis
|
0.54%
1/184
|
0.00%
0/172
|
|
Infections and infestations
Fungal infection
|
0.54%
1/184
|
0.00%
0/172
|
|
Infections and infestations
Gastroenteritis
|
1.1%
2/184
|
0.00%
0/172
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/184
|
0.58%
1/172
|
|
Infections and infestations
Groin abscess
|
0.54%
1/184
|
0.00%
0/172
|
|
Infections and infestations
Hepatic infection
|
0.54%
1/184
|
0.00%
0/172
|
|
Infections and infestations
Hepatitis C
|
41.8%
77/184
|
37.8%
65/172
|
|
Infections and infestations
Herpes zoster
|
0.54%
1/184
|
0.00%
0/172
|
|
Infections and infestations
Infective exacerbation of chronic obstructive airways disease
|
0.54%
1/184
|
0.00%
0/172
|
|
Infections and infestations
Intervertebral discitis
|
0.00%
0/184
|
0.58%
1/172
|
|
Infections and infestations
Liver abscess
|
1.6%
3/184
|
0.00%
0/172
|
|
Infections and infestations
Lung infection
|
0.00%
0/184
|
0.58%
1/172
|
|
Infections and infestations
Neurological infection
|
0.54%
1/184
|
0.00%
0/172
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/184
|
0.58%
1/172
|
|
Infections and infestations
Pericarditis fungal
|
0.00%
0/184
|
0.58%
1/172
|
|
Infections and infestations
Peritonitis bacterial
|
0.54%
1/184
|
0.58%
1/172
|
|
Infections and infestations
Pneumonia
|
1.1%
2/184
|
4.1%
7/172
|
|
Infections and infestations
Pneumonia bacterial
|
0.54%
1/184
|
0.00%
0/172
|
|
Infections and infestations
Respiratory tract infection
|
0.54%
1/184
|
0.00%
0/172
|
|
Infections and infestations
Sepsis
|
4.3%
8/184
|
2.9%
5/172
|
|
Infections and infestations
Septic shock
|
0.00%
0/184
|
1.2%
2/172
|
|
Infections and infestations
Sinusitis
|
0.54%
1/184
|
0.00%
0/172
|
|
Infections and infestations
Staphylococcal sepsis
|
0.00%
0/184
|
0.58%
1/172
|
|
Infections and infestations
Tuberculosis liver
|
0.00%
0/184
|
0.58%
1/172
|
|
Infections and infestations
Urinary tract infection
|
0.54%
1/184
|
1.7%
3/172
|
|
Infections and infestations
Wound infection
|
0.00%
0/184
|
0.58%
1/172
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.54%
1/184
|
0.00%
0/172
|
|
Injury, poisoning and procedural complications
Biliary anastomosis complication
|
0.54%
1/184
|
2.3%
4/172
|
|
Injury, poisoning and procedural complications
Chemical peritonitis
|
1.1%
2/184
|
0.00%
0/172
|
|
Injury, poisoning and procedural complications
Collapse of lung
|
0.54%
1/184
|
0.00%
0/172
|
|
Injury, poisoning and procedural complications
Complications of transplanted liver
|
1.6%
3/184
|
5.8%
10/172
|
|
Injury, poisoning and procedural complications
Gastrointestinal injury
|
0.00%
0/184
|
0.58%
1/172
|
|
Injury, poisoning and procedural complications
Graft loss
|
0.54%
1/184
|
0.58%
1/172
|
|
Injury, poisoning and procedural complications
Hepatic haematoma
|
1.6%
3/184
|
0.00%
0/172
|
|
Injury, poisoning and procedural complications
Incision site haemorrhage
|
0.54%
1/184
|
0.00%
0/172
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
1.6%
3/184
|
0.58%
1/172
|
|
Injury, poisoning and procedural complications
Limb traumatic amputation
|
0.00%
0/184
|
0.58%
1/172
|
|
Injury, poisoning and procedural complications
Post procedural bile leak
|
2.7%
5/184
|
2.3%
4/172
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
1.1%
2/184
|
0.58%
1/172
|
|
Injury, poisoning and procedural complications
Postoperative fever
|
0.54%
1/184
|
0.00%
0/172
|
|
Injury, poisoning and procedural complications
Procedural site reaction
|
0.00%
0/184
|
0.58%
1/172
|
|
Injury, poisoning and procedural complications
Seroma
|
0.00%
0/184
|
0.58%
1/172
|
|
Injury, poisoning and procedural complications
Skin laceration
|
0.00%
0/184
|
0.58%
1/172
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.54%
1/184
|
0.00%
0/172
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.54%
1/184
|
0.00%
0/172
|
|
Injury, poisoning and procedural complications
Therapeutic agent toxicity
|
0.54%
1/184
|
1.2%
2/172
|
|
Injury, poisoning and procedural complications
Vascular pseudoaneurysm
|
0.54%
1/184
|
0.00%
0/172
|
|
Injury, poisoning and procedural complications
Wound decomposition
|
0.54%
1/184
|
0.00%
0/172
|
|
Investigations
Blood bilirubin increased
|
0.54%
1/184
|
1.2%
2/172
|
|
Investigations
Blood creatine phosphokinase increased
|
0.54%
1/184
|
0.00%
0/172
|
|
Investigations
Blood creatinine increased
|
1.6%
3/184
|
0.00%
0/172
|
|
Investigations
Blood pressure increased
|
0.54%
1/184
|
0.00%
0/172
|
|
Investigations
Hepatic enzyme increased
|
0.54%
1/184
|
1.2%
2/172
|
|
Investigations
Hepatitis C virus test positive
|
0.54%
1/184
|
0.00%
0/172
|
|
Investigations
Liver function test abnormal
|
7.6%
14/184
|
5.2%
9/172
|
|
Investigations
Transaminases increased
|
1.1%
2/184
|
0.00%
0/172
|
|
Metabolism and nutrition disorders
Dehydration
|
0.54%
1/184
|
0.58%
1/172
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.00%
0/184
|
2.3%
4/172
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.00%
0/184
|
0.58%
1/172
|
|
Metabolism and nutrition disorders
Fluid overload
|
0.00%
0/184
|
0.58%
1/172
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/184
|
0.58%
1/172
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.54%
1/184
|
0.58%
1/172
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
0.00%
0/184
|
0.58%
1/172
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.54%
1/184
|
0.00%
0/172
|
|
Metabolism and nutrition disorders
Type 2 diabetes mellitus
|
0.54%
1/184
|
0.00%
0/172
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.54%
1/184
|
1.7%
3/172
|
|
Musculoskeletal and connective tissue disorders
Myositis
|
0.00%
0/184
|
0.58%
1/172
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma
|
0.54%
1/184
|
0.00%
0/172
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic cancer metastatic
|
0.00%
0/184
|
0.58%
1/172
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic neoplasm malignant
|
0.54%
1/184
|
0.58%
1/172
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm
|
0.54%
1/184
|
0.00%
0/172
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.54%
1/184
|
0.00%
0/172
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphoma
|
0.00%
0/184
|
1.2%
2/172
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to lung
|
0.54%
1/184
|
0.00%
0/172
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-Hodgkin's lymphoma
|
0.54%
1/184
|
0.00%
0/172
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.54%
1/184
|
0.00%
0/172
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seminoma
|
0.00%
0/184
|
0.58%
1/172
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tongue neoplasm malignant stage unspecified
|
0.00%
0/184
|
0.58%
1/172
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Transitional cell carcinoma
|
0.54%
1/184
|
0.00%
0/172
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/184
|
0.58%
1/172
|
|
Nervous system disorders
Cerebral ischaemia
|
0.54%
1/184
|
0.00%
0/172
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/184
|
0.58%
1/172
|
|
Nervous system disorders
Convulsion
|
1.1%
2/184
|
0.58%
1/172
|
|
Nervous system disorders
Dizziness
|
0.00%
0/184
|
1.2%
2/172
|
|
Nervous system disorders
Encephalopathy
|
1.1%
2/184
|
0.00%
0/172
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.54%
1/184
|
0.00%
0/172
|
|
Nervous system disorders
Haemorrhagic stroke
|
0.54%
1/184
|
0.58%
1/172
|
|
Nervous system disorders
Headache
|
0.54%
1/184
|
0.58%
1/172
|
|
Nervous system disorders
Hypertensive encephalopathy
|
0.54%
1/184
|
0.00%
0/172
|
|
Nervous system disorders
Migraine
|
0.00%
0/184
|
0.58%
1/172
|
|
Nervous system disorders
Neurological symptom
|
0.54%
1/184
|
0.00%
0/172
|
|
Nervous system disorders
Neurotoxicity
|
0.54%
1/184
|
1.2%
2/172
|
|
Nervous system disorders
Reversible posterior leukoencephalopathy syndrome
|
0.54%
1/184
|
0.00%
0/172
|
|
Nervous system disorders
Somnolence
|
0.00%
0/184
|
0.58%
1/172
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.54%
1/184
|
0.58%
1/172
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/184
|
0.58%
1/172
|
|
Nervous system disorders
Tremor
|
0.00%
0/184
|
0.58%
1/172
|
|
Psychiatric disorders
Alcoholism
|
0.00%
0/184
|
0.58%
1/172
|
|
Psychiatric disorders
Delirium
|
0.54%
1/184
|
0.00%
0/172
|
|
Psychiatric disorders
Mental status changes
|
1.6%
3/184
|
0.58%
1/172
|
|
Psychiatric disorders
Psychotic disorder
|
1.1%
2/184
|
0.00%
0/172
|
|
Psychiatric disorders
Substance abuse
|
0.00%
0/184
|
0.58%
1/172
|
|
Psychiatric disorders
Transient psychosis
|
1.6%
3/184
|
0.00%
0/172
|
|
Renal and urinary disorders
Acute prerenal failure
|
0.00%
0/184
|
0.58%
1/172
|
|
Renal and urinary disorders
Anuria
|
0.00%
0/184
|
0.58%
1/172
|
|
Renal and urinary disorders
Nephrotic syndrome
|
0.54%
1/184
|
0.00%
0/172
|
|
Renal and urinary disorders
Renal failure
|
3.3%
6/184
|
1.7%
3/172
|
|
Renal and urinary disorders
Renal failure acute
|
7.6%
14/184
|
3.5%
6/172
|
|
Renal and urinary disorders
Renal impairment
|
1.1%
2/184
|
1.2%
2/172
|
|
Renal and urinary disorders
Renal tubular necrosis
|
0.54%
1/184
|
0.00%
0/172
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.00%
0/184
|
0.58%
1/172
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/184
|
0.58%
1/172
|
|
Respiratory, thoracic and mediastinal disorders
Brain hypoxia
|
0.00%
0/184
|
0.58%
1/172
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/184
|
0.58%
1/172
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.54%
1/184
|
0.00%
0/172
|
|
Respiratory, thoracic and mediastinal disorders
Haemothorax
|
0.54%
1/184
|
0.00%
0/172
|
|
Respiratory, thoracic and mediastinal disorders
Hyperventilation
|
0.54%
1/184
|
0.00%
0/172
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
2.7%
5/184
|
1.2%
2/172
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.00%
0/184
|
0.58%
1/172
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.54%
1/184
|
0.00%
0/172
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.54%
1/184
|
1.2%
2/172
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/184
|
0.58%
1/172
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.54%
1/184
|
0.00%
0/172
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.7%
5/184
|
2.9%
5/172
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
0.00%
0/184
|
0.58%
1/172
|
|
Skin and subcutaneous tissue disorders
Stasis dermatitis
|
0.54%
1/184
|
0.00%
0/172
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/184
|
1.2%
2/172
|
|
Vascular disorders
Haemodynamic instability
|
0.54%
1/184
|
0.00%
0/172
|
|
Vascular disorders
Hypertension
|
0.00%
0/184
|
0.58%
1/172
|
|
Vascular disorders
Hypertensive crisis
|
0.54%
1/184
|
0.58%
1/172
|
|
Vascular disorders
Hypotension
|
1.1%
2/184
|
0.00%
0/172
|
|
Vascular disorders
Intra-abdominal haematoma
|
0.54%
1/184
|
0.00%
0/172
|
|
Vascular disorders
Intra-abdominal haemorrhage
|
1.1%
2/184
|
1.2%
2/172
|
|
Vascular disorders
Malignant hypertension
|
0.54%
1/184
|
0.58%
1/172
|
|
Vascular disorders
Thrombosis
|
0.00%
0/184
|
0.58%
1/172
|
|
Vascular disorders
Venoocclusive disease
|
0.00%
0/184
|
0.58%
1/172
|
|
Vascular disorders
Venous thrombosis
|
0.00%
0/184
|
0.58%
1/172
|
Other adverse events
| Measure |
Cyclosporin A
n=184 participants at risk
The first administration of Cyclosporin A (CsA) was within the first 24 hours post-transplantation at an initial dose of 10-15mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally, via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the study, it was recommended that the dose of CsA was adjusted, as necessary, to achieve and maintain the C2 or C0 blood CsA concentration within the target ranges.
|
Tacrolimus
n=172 participants at risk
Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
27.7%
51/184
|
31.4%
54/172
|
|
Blood and lymphatic system disorders
Coagulopathy
|
1.6%
3/184
|
5.2%
9/172
|
|
Blood and lymphatic system disorders
Leukopenia
|
9.2%
17/184
|
5.8%
10/172
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
12.5%
23/184
|
16.3%
28/172
|
|
Gastrointestinal disorders
Abdominal distension
|
7.6%
14/184
|
4.1%
7/172
|
|
Gastrointestinal disorders
Abdominal pain
|
16.8%
31/184
|
25.6%
44/172
|
|
Gastrointestinal disorders
Abdominal pain upper
|
4.9%
9/184
|
8.1%
14/172
|
|
Gastrointestinal disorders
Ascites
|
16.8%
31/184
|
16.9%
29/172
|
|
Gastrointestinal disorders
Constipation
|
34.8%
64/184
|
36.0%
62/172
|
|
Gastrointestinal disorders
Diarrhoea
|
22.3%
41/184
|
33.1%
57/172
|
|
Gastrointestinal disorders
Dyspepsia
|
8.2%
15/184
|
8.1%
14/172
|
|
Gastrointestinal disorders
Nausea
|
29.9%
55/184
|
34.3%
59/172
|
|
Gastrointestinal disorders
Vomiting
|
16.3%
30/184
|
14.5%
25/172
|
|
General disorders
Asthenia
|
8.2%
15/184
|
5.2%
9/172
|
|
General disorders
Fatigue
|
13.0%
24/184
|
11.0%
19/172
|
|
General disorders
Generalised oedema
|
6.5%
12/184
|
7.0%
12/172
|
|
General disorders
Non-cardiac chest pain
|
3.8%
7/184
|
7.6%
13/172
|
|
General disorders
Oedema peripheral
|
33.2%
61/184
|
33.7%
58/172
|
|
General disorders
Pyrexia
|
28.3%
52/184
|
27.3%
47/172
|
|
Hepatobiliary disorders
Bile duct stenosis
|
6.0%
11/184
|
7.0%
12/172
|
|
Hepatobiliary disorders
Cholestasis
|
5.4%
10/184
|
5.8%
10/172
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
7.1%
13/184
|
4.1%
7/172
|
|
Infections and infestations
Cytomegalovirus infection
|
8.7%
16/184
|
2.9%
5/172
|
|
Infections and infestations
Hepatitis C
|
10.3%
19/184
|
12.2%
21/172
|
|
Infections and infestations
Nasopharyngitis
|
5.4%
10/184
|
7.6%
13/172
|
|
Infections and infestations
Pneumonia
|
3.3%
6/184
|
8.7%
15/172
|
|
Infections and infestations
Urinary tract infection
|
13.0%
24/184
|
9.3%
16/172
|
|
Injury, poisoning and procedural complications
Incision site pain
|
17.9%
33/184
|
15.7%
27/172
|
|
Injury, poisoning and procedural complications
Post procedural bile leak
|
4.3%
8/184
|
5.2%
9/172
|
|
Injury, poisoning and procedural complications
Post procedural discharge
|
3.3%
6/184
|
5.8%
10/172
|
|
Injury, poisoning and procedural complications
Procedural pain
|
27.2%
50/184
|
34.3%
59/172
|
|
Investigations
Blood bilirubin increased
|
8.2%
15/184
|
3.5%
6/172
|
|
Investigations
Blood creatinine increased
|
19.0%
35/184
|
13.4%
23/172
|
|
Investigations
Blood glucose increased
|
2.2%
4/184
|
5.2%
9/172
|
|
Investigations
Blood potassium decreased
|
5.4%
10/184
|
5.2%
9/172
|
|
Investigations
Haemoglobin decreased
|
4.3%
8/184
|
6.4%
11/172
|
|
Investigations
Liver function test abnormal
|
16.8%
31/184
|
14.5%
25/172
|
|
Investigations
Urine output decreased
|
9.2%
17/184
|
9.3%
16/172
|
|
Metabolism and nutrition disorders
Decreased appetite
|
11.4%
21/184
|
9.3%
16/172
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
14.1%
26/184
|
16.3%
28/172
|
|
Metabolism and nutrition disorders
Fluid overload
|
6.0%
11/184
|
7.6%
13/172
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
25.0%
46/184
|
28.5%
49/172
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
14.7%
27/184
|
16.3%
28/172
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
7.1%
13/184
|
8.1%
14/172
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
9.2%
17/184
|
9.9%
17/172
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
17.9%
33/184
|
16.9%
29/172
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
21.2%
39/184
|
25.0%
43/172
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
6.0%
11/184
|
3.5%
6/172
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.4%
10/184
|
6.4%
11/172
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
20.7%
38/184
|
14.5%
25/172
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.0%
11/184
|
9.3%
16/172
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
7.1%
13/184
|
2.9%
5/172
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.0%
11/184
|
8.1%
14/172
|
|
Nervous system disorders
Dizziness
|
4.3%
8/184
|
6.4%
11/172
|
|
Nervous system disorders
Headache
|
24.5%
45/184
|
22.7%
39/172
|
|
Nervous system disorders
Tremor
|
14.1%
26/184
|
17.4%
30/172
|
|
Psychiatric disorders
Agitation
|
8.7%
16/184
|
14.0%
24/172
|
|
Psychiatric disorders
Anxiety
|
16.3%
30/184
|
12.2%
21/172
|
|
Psychiatric disorders
Confusional state
|
4.9%
9/184
|
8.7%
15/172
|
|
Psychiatric disorders
Depression
|
9.2%
17/184
|
9.3%
16/172
|
|
Psychiatric disorders
Insomnia
|
35.3%
65/184
|
37.2%
64/172
|
|
Renal and urinary disorders
Oliguria
|
12.0%
22/184
|
11.6%
20/172
|
|
Renal and urinary disorders
Renal failure
|
10.3%
19/184
|
10.5%
18/172
|
|
Renal and urinary disorders
Renal failure acute
|
12.5%
23/184
|
9.3%
16/172
|
|
Renal and urinary disorders
Renal impairment
|
11.4%
21/184
|
8.7%
15/172
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
6.0%
11/184
|
6.4%
11/172
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.6%
14/184
|
8.1%
14/172
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
12.0%
22/184
|
14.0%
24/172
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
13.6%
25/184
|
18.0%
31/172
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
3.8%
7/184
|
5.2%
9/172
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
11.4%
21/184
|
11.0%
19/172
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.0%
11/184
|
2.9%
5/172
|
|
Vascular disorders
Hypertension
|
50.0%
92/184
|
40.1%
69/172
|
|
Vascular disorders
Hypotension
|
10.9%
20/184
|
8.7%
15/172
|
Additional Information
Study coordinator
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER