Trial Outcomes & Findings for Cyclosporine A C-2h Monitoring Versus Tacrolimus C-0h Monitoring in de Novo Liver Transplant Recipients (NCT NCT00149994)
NCT ID: NCT00149994
Last Updated: 2011-04-12
Results Overview
A BPAR is defined when the investigator had a suspicion of an acute rejection, where the final clinical diagnosis confirmed the occurrence of an acute rejection, where a biopsy was performed that confirmed the presence of an acute rejection, and where anti-rejection treatment intervention was initiated. The efficacy measured the first rejections (clinically and biopsy proven rejections) at 3 months.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
171 participants
Primary outcome timeframe
Month 3
Results posted on
2011-04-12
Participant Flow
Participant milestones
| Measure |
Cyclosporine A
Cyclosporine A was given twice-daily at 12-hour intervals. It was administered within the first 4 hours post-operatively (study day 1), at an initial dose of 10-15mg/kg/day in two doses. Cyclosporine A was adjusted to bring the 2 hour after oral dose (C-2h) level into the target range by Days 3-5 post-transplantation. The dose of Cyclosporine A was adjusted to achieve and maintain post transplantation C-2h levels 0- 3 months: 800- 1200 ng/mL, 4- 6 months: 700- 900 ng/mL and \>6 months: 500- 700 ng/mL. Each participant was given two 20 mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery. Methylprednisolone was given as an intravenous bolus of 500 mg during transplant surgery. Post-operatively prednisone was tapered from an initial dose of 20 mg/day to zero at 3 months or continued at 5-10 mg if the indication for Orthotopic Liver Transplantation (OLTx) was of auto-immune nature.
|
Tacrolimus
Tacrolimus was given twice-daily at 12-hour intervals. Tacrolimus was administered within the first 24 hrs post- operatively (Study Day 1) at an initial dose of 0.1-0.15 mg/kg/day in two divided oral doses either by mouth or via an enteral feeding tube until the participant can swallow. The initial dosing level was determined by the participants's overall post-operative condition. The dose of tacrolimus was adjusted to achieve and maintain the pre-dose C-Oh (trough) target ranges post-transplantation 0-3 months: 10-15 ng/ml; 4-6 months: 5-10 ng/ml and \> 6 months: 5-10 ng/ml . Each participant was given two 20 mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery. Methylprednisolone was given as an intravenous bolus of 500 mg during transplant surgery. Post-operatively prednisone was tapered from an initial dose of 20 mg/day to zero at 3 months or continued at 5-10 mg if the indication for OLTx was of auto-immune in nature.
|
|---|---|---|
|
Overall Study
STARTED
|
85
|
86
|
|
Overall Study
COMPLETED
|
84
|
85
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Cyclosporine A
Cyclosporine A was given twice-daily at 12-hour intervals. It was administered within the first 4 hours post-operatively (study day 1), at an initial dose of 10-15mg/kg/day in two doses. Cyclosporine A was adjusted to bring the 2 hour after oral dose (C-2h) level into the target range by Days 3-5 post-transplantation. The dose of Cyclosporine A was adjusted to achieve and maintain post transplantation C-2h levels 0- 3 months: 800- 1200 ng/mL, 4- 6 months: 700- 900 ng/mL and \>6 months: 500- 700 ng/mL. Each participant was given two 20 mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery. Methylprednisolone was given as an intravenous bolus of 500 mg during transplant surgery. Post-operatively prednisone was tapered from an initial dose of 20 mg/day to zero at 3 months or continued at 5-10 mg if the indication for Orthotopic Liver Transplantation (OLTx) was of auto-immune nature.
|
Tacrolimus
Tacrolimus was given twice-daily at 12-hour intervals. Tacrolimus was administered within the first 24 hrs post- operatively (Study Day 1) at an initial dose of 0.1-0.15 mg/kg/day in two divided oral doses either by mouth or via an enteral feeding tube until the participant can swallow. The initial dosing level was determined by the participants's overall post-operative condition. The dose of tacrolimus was adjusted to achieve and maintain the pre-dose C-Oh (trough) target ranges post-transplantation 0-3 months: 10-15 ng/ml; 4-6 months: 5-10 ng/ml and \> 6 months: 5-10 ng/ml . Each participant was given two 20 mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery. Methylprednisolone was given as an intravenous bolus of 500 mg during transplant surgery. Post-operatively prednisone was tapered from an initial dose of 20 mg/day to zero at 3 months or continued at 5-10 mg if the indication for OLTx was of auto-immune in nature.
|
|---|---|---|
|
Overall Study
Administrative problems:
|
1
|
0
|
|
Overall Study
Protocol Violation
|
0
|
1
|
Baseline Characteristics
Cyclosporine A C-2h Monitoring Versus Tacrolimus C-0h Monitoring in de Novo Liver Transplant Recipients
Baseline characteristics by cohort
| Measure |
Cyclosporine A
n=84 Participants
Cyclosporine A was given twice-daily at 12-hour intervals. It was administered within the first 4 hours post-operatively (study day 1), at an initial dose of 10-15mg/kg/day in two doses. Cyclosporine A was adjusted to bring the 2 hour after oral dose (C-2h) level into the target range by Days 3-5 post-transplantation. The dose of Cyclosporine A was adjusted to achieve and maintain post transplantation C-2h levels 0- 3 months: 800- 1200 ng/mL, 4- 6 months: 700- 900 ng/mL and \>6 months: 500- 700 ng/mL. Each participant was given two 20 mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery. Methylprednisolone was given as an intravenous bolus of 500 mg during transplant surgery. Post-operatively prednisone was tapered from an initial dose of 20 mg/day to zero at 3 months or continued at 5-10 mg if the indication for Orthotopic Liver Transplantation (OLTx) was of auto-immune nature.
|
Tacrolimus
n=85 Participants
Tacrolimus was given twice-daily at 12-hour intervals. Tacrolimus was administered within the first 24 hrs post- operatively (Study Day 1) at an initial dose of 0.1-0.15 mg/kg/day in two divided oral doses either by mouth or via an enteral feeding tube until the participant can swallow. The initial dosing level was determined by the participants's overall post-operative condition. The dose of tacrolimus was adjusted to achieve and maintain the pre-dose C-Oh (trough) target ranges post-transplantation 0-3 months: 10-15 ng/ml; 4-6 months: 5-10 ng/ml and \> 6 months: 5-10 ng/ml . Each participant was given two 20 mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery. Methylprednisolone was given as an intravenous bolus of 500 mg during transplant surgery. Post-operatively prednisone was tapered from an initial dose of 20 mg/day to zero at 3 months or continued at 5-10 mg if the indication for OLTx was of auto-immune in nature.
|
Total
n=169 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
48.1 Years
STANDARD_DEVIATION 12.069 • n=5 Participants
|
49.9 Years
STANDARD_DEVIATION 9.886 • n=7 Participants
|
48.98 Years
STANDARD_DEVIATION 11.029 • n=5 Participants
|
|
Sex: Female, Male
Female
|
31 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
53 Participants
n=5 Participants
|
55 Participants
n=7 Participants
|
108 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Month 3Population: Intention to treat (ITT) population.
A BPAR is defined when the investigator had a suspicion of an acute rejection, where the final clinical diagnosis confirmed the occurrence of an acute rejection, where a biopsy was performed that confirmed the presence of an acute rejection, and where anti-rejection treatment intervention was initiated. The efficacy measured the first rejections (clinically and biopsy proven rejections) at 3 months.
Outcome measures
| Measure |
Cyclosporine A
n=84 Participants
Cyclosporine A was given twice-daily at 12-hour intervals. It was administered within the first 4 hours post-operatively (study day 1), at an initial dose of 10-15mg/kg/day in two doses. Cyclosporine A was adjusted to bring the 2 hour after oral dose (C-2h) level into the target range by Days 3-5 post-transplantation. The dose of Cyclosporine A was adjusted to achieve and maintain post transplantation C-2h levels 0- 3 months: 800- 1200 ng/mL, 4- 6 months: 700- 900 ng/mL and \>6 months: 500- 700 ng/mL. Each participant was given two 20 mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery. Methylprednisolone was given as an intravenous bolus of 500 mg during transplant surgery. Post-operatively prednisone was tapered from an initial dose of 20 mg/day to zero at 3 months or continued at 5-10 mg if the indication for Orthotopic Liver Transplantation (OLTx) was of auto-immune nature.
|
Tacrolimus
n=85 Participants
Tacrolimus was given twice-daily at 12-hour intervals. Tacrolimus was administered within the first 24 hrs post- operatively (Study Day 1) at an initial dose of 0.1-0.15 mg/kg/day in two divided oral doses either by mouth or via an enteral feeding tube until the participant can swallow. The initial dosing level was determined by the participants's overall post-operative condition. The dose of tacrolimus was adjusted to achieve and maintain the pre-dose C-Oh (trough) target ranges post-transplantation 0-3 months: 10-15 ng/ml; 4-6 months: 5-10 ng/ml and \> 6 months: 5-10 ng/ml . Each participant was given two 20 mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery. Methylprednisolone was given as an intravenous bolus of 500 mg during transplant surgery. Post-operatively prednisone was tapered from an initial dose of 20 mg/day to zero at 3 months or continued at 5-10 mg if the indication for OLTx was of auto-immune in nature.
|
|---|---|---|
|
Percentage of Participants With an Occurrence of Biopsy Proven Acute Rejection (BPAR) During the First 3 Months Post de Novo Liver Transplantation.
|
33.3 Percentage of Participants
|
32.9 Percentage of Participants
|
Adverse Events
Tacrolimus
Serious events: 42 serious events
Other events: 84 other events
Deaths: 0 deaths
Cyclosporine A
Serious events: 33 serious events
Other events: 85 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Tacrolimus
n=86 participants at risk
Tacrolimus was given twice-daily at 12-hour intervals. Tacrolimus was administered within the first 24 hrs post- operatively (Study Day 1) at an initial dose of 0.1-0.15 mg/kg/day in two divided oral doses either by mouth or via an enteral feeding tube until the participant can swallow. The initial dosing level was determined by the participants's overall post-operative condition. The dose of tacrolimus was adjusted to achieve and maintain the pre-dose C-Oh (trough) target ranges post-transplantation 0-3 months: 10-15 ng/ml; 4-6 months: 5-10 ng/ml and \> 6 months: 5-10 ng/ml . Each participant was given two 20 mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery. Methylprednisolone was given as an intravenous bolus of 500 mg during transplant surgery. Post-operatively prednisone was tapered from an initial dose of 20 mg/day to zero at 3 months or continued at 5-10 mg if the indication for OLTx was of auto-immune in nature.
|
Cyclosporine A
n=85 participants at risk
Cyclosporine A was given twice-daily at 12-hour intervals. It was administered within the first 4 hours post-operatively (study day 1), at an initial dose of 10-15mg/kg/day in two doses. Cyclosporine A was adjusted to bring the 2 hour after oral dose (C-2h) level into the target range by Days 3-5 post-transplantation. The dose of Cyclosporine A was adjusted to achieve and maintain post transplantation C-2h levels 0- 3 months: 800- 1200 ng/mL, 4- 6 months: 700- 900 ng/mL and \>6 months: 500- 700 ng/mL. Each participant was given two 20 mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery. Methylprednisolone was given as an intravenous bolus of 500 mg during transplant surgery. Post-operatively prednisone was tapered from an initial dose of 20 mg/day to zero at 3 months or continued at 5-10 mg if the indication for Orthotopic Liver Transplantation (OLTx) was of auto-immune nature.
|
|---|---|---|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Cardiac disorders
Arrhythmia
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Cardiac disorders
Cardiac arrest
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Cardiac disorders
Myocardial infarction
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Gastrointestinal disorders
Abdominal pain
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.2%
1/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/86 • Up to 6 months
|
2.4%
2/85 • Up to 6 months
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Gastrointestinal disorders
Crohn's disease
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/86 • Up to 6 months
|
2.4%
2/85 • Up to 6 months
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Gastrointestinal disorders
Gastrointestinal necrosis
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Gastrointestinal disorders
Megacolon
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Gastrointestinal disorders
Nausea
|
2.3%
2/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Gastrointestinal disorders
Truncus coeliacus thrombosis
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Gastrointestinal disorders
Vomiting
|
3.5%
3/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
General disorders
Chest pain
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
General disorders
Chills
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
General disorders
Malaise
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
General disorders
Pain
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
General disorders
Pyrexia
|
12.8%
11/86 • Up to 6 months
|
4.7%
4/85 • Up to 6 months
|
|
Hepatobiliary disorders
Biliary dilatation
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Hepatobiliary disorders
Biliary ischaemia
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Hepatobiliary disorders
Biloma
|
2.3%
2/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Hepatobiliary disorders
Cholangitis
|
3.5%
3/86 • Up to 6 months
|
2.4%
2/85 • Up to 6 months
|
|
Hepatobiliary disorders
Cholestasis
|
0.00%
0/86 • Up to 6 months
|
2.4%
2/85 • Up to 6 months
|
|
Hepatobiliary disorders
Hepatic artery thrombosis
|
1.2%
1/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Hepatobiliary disorders
Hepatic failure
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Hepatobiliary disorders
Hepatic haemorrhage
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Hepatobiliary disorders
Hepatic necrosis
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Hepatobiliary disorders
Jaundice
|
1.2%
1/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Hepatobiliary disorders
Liver function test abnormal
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Hepatobiliary disorders
Liver injury
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
2.3%
2/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Immune system disorders
Graft versus host disease
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Infections and infestations
Cytomegalovirus colitis
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Infections and infestations
Cytomegalovirus infection
|
2.3%
2/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Infections and infestations
Hepatitis C
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Infections and infestations
Liver abscess
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Infections and infestations
Pneumonia
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Infections and infestations
Sepsis
|
2.3%
2/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Infections and infestations
Septic shock
|
1.2%
1/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Infections and infestations
Urinary tract infection
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Injury, poisoning and procedural complications
Biliary anastomosis complication
|
3.5%
3/86 • Up to 6 months
|
3.5%
3/85 • Up to 6 months
|
|
Injury, poisoning and procedural complications
Hepatic haematoma
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Injury, poisoning and procedural complications
Transplant failure
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Investigations
Transaminases increased
|
2.3%
2/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Metabolism and nutrition disorders
Dehydration
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/86 • Up to 6 months
|
2.4%
2/85 • Up to 6 months
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Metabolism and nutrition disorders
Ketoacidosis
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.3%
2/86 • Up to 6 months
|
2.4%
2/85 • Up to 6 months
|
|
Musculoskeletal and connective tissue disorders
Compartment syndrome
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Nervous system disorders
Amnesia
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Nervous system disorders
Cerebral haemorrhage
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Nervous system disorders
Convulsion
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Nervous system disorders
Neurotoxicity
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Psychiatric disorders
Completed suicide
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Renal and urinary disorders
Nephropathy toxic
|
0.00%
0/86 • Up to 6 months
|
2.4%
2/85 • Up to 6 months
|
|
Renal and urinary disorders
Oliguria
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Renal and urinary disorders
Renal failure
|
1.2%
1/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Renal and urinary disorders
Renal impairment
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Brain hypoxia
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.2%
1/86 • Up to 6 months
|
2.4%
2/85 • Up to 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.2%
1/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
2.3%
2/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.2%
1/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Stridor
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Skin and subcutaneous tissue disorders
Dermatitis herpetiformis
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.2%
1/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Vascular disorders
Arterial haemorrhage
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Vascular disorders
Hypovolaemic shock
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Vascular disorders
Intra-abdominal haemorrhage
|
0.00%
0/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Vascular disorders
Shock haemorrhagic
|
1.2%
1/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
Other adverse events
| Measure |
Tacrolimus
n=86 participants at risk
Tacrolimus was given twice-daily at 12-hour intervals. Tacrolimus was administered within the first 24 hrs post- operatively (Study Day 1) at an initial dose of 0.1-0.15 mg/kg/day in two divided oral doses either by mouth or via an enteral feeding tube until the participant can swallow. The initial dosing level was determined by the participants's overall post-operative condition. The dose of tacrolimus was adjusted to achieve and maintain the pre-dose C-Oh (trough) target ranges post-transplantation 0-3 months: 10-15 ng/ml; 4-6 months: 5-10 ng/ml and \> 6 months: 5-10 ng/ml . Each participant was given two 20 mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery. Methylprednisolone was given as an intravenous bolus of 500 mg during transplant surgery. Post-operatively prednisone was tapered from an initial dose of 20 mg/day to zero at 3 months or continued at 5-10 mg if the indication for OLTx was of auto-immune in nature.
|
Cyclosporine A
n=85 participants at risk
Cyclosporine A was given twice-daily at 12-hour intervals. It was administered within the first 4 hours post-operatively (study day 1), at an initial dose of 10-15mg/kg/day in two doses. Cyclosporine A was adjusted to bring the 2 hour after oral dose (C-2h) level into the target range by Days 3-5 post-transplantation. The dose of Cyclosporine A was adjusted to achieve and maintain post transplantation C-2h levels 0- 3 months: 800- 1200 ng/mL, 4- 6 months: 700- 900 ng/mL and \>6 months: 500- 700 ng/mL. Each participant was given two 20 mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery. Methylprednisolone was given as an intravenous bolus of 500 mg during transplant surgery. Post-operatively prednisone was tapered from an initial dose of 20 mg/day to zero at 3 months or continued at 5-10 mg if the indication for Orthotopic Liver Transplantation (OLTx) was of auto-immune nature.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
23.3%
20/86 • Up to 6 months
|
32.9%
28/85 • Up to 6 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.8%
5/86 • Up to 6 months
|
8.2%
7/85 • Up to 6 months
|
|
Cardiac disorders
Cardiac failure
|
5.8%
5/86 • Up to 6 months
|
4.7%
4/85 • Up to 6 months
|
|
Cardiac disorders
Tachycardia
|
5.8%
5/86 • Up to 6 months
|
8.2%
7/85 • Up to 6 months
|
|
Gastrointestinal disorders
Abdominal pain
|
16.3%
14/86 • Up to 6 months
|
28.2%
24/85 • Up to 6 months
|
|
Gastrointestinal disorders
Abdominal pain upper
|
11.6%
10/86 • Up to 6 months
|
10.6%
9/85 • Up to 6 months
|
|
Gastrointestinal disorders
Ascites
|
33.7%
29/86 • Up to 6 months
|
41.2%
35/85 • Up to 6 months
|
|
Gastrointestinal disorders
Constipation
|
30.2%
26/86 • Up to 6 months
|
37.6%
32/85 • Up to 6 months
|
|
Gastrointestinal disorders
Diarrhoea
|
30.2%
26/86 • Up to 6 months
|
63.5%
54/85 • Up to 6 months
|
|
Gastrointestinal disorders
Dyspepsia
|
4.7%
4/86 • Up to 6 months
|
5.9%
5/85 • Up to 6 months
|
|
Gastrointestinal disorders
Ileus
|
7.0%
6/86 • Up to 6 months
|
2.4%
2/85 • Up to 6 months
|
|
Gastrointestinal disorders
Impaired gastric emptying
|
2.3%
2/86 • Up to 6 months
|
8.2%
7/85 • Up to 6 months
|
|
Gastrointestinal disorders
Nausea
|
46.5%
40/86 • Up to 6 months
|
45.9%
39/85 • Up to 6 months
|
|
Gastrointestinal disorders
Vomiting
|
29.1%
25/86 • Up to 6 months
|
30.6%
26/85 • Up to 6 months
|
|
General disorders
Chest pain
|
8.1%
7/86 • Up to 6 months
|
3.5%
3/85 • Up to 6 months
|
|
General disorders
Fatigue
|
9.3%
8/86 • Up to 6 months
|
14.1%
12/85 • Up to 6 months
|
|
General disorders
Oedema
|
47.7%
41/86 • Up to 6 months
|
43.5%
37/85 • Up to 6 months
|
|
General disorders
Pain
|
9.3%
8/86 • Up to 6 months
|
11.8%
10/85 • Up to 6 months
|
|
General disorders
Pyrexia
|
29.1%
25/86 • Up to 6 months
|
38.8%
33/85 • Up to 6 months
|
|
Hepatobiliary disorders
Biloma
|
5.8%
5/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Hepatobiliary disorders
Cholestasis
|
4.7%
4/86 • Up to 6 months
|
9.4%
8/85 • Up to 6 months
|
|
Hepatobiliary disorders
Jaundice
|
7.0%
6/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Infections and infestations
- Unknown Infections -
|
26.7%
23/86 • Up to 6 months
|
21.2%
18/85 • Up to 6 months
|
|
Infections and infestations
Candidiasis
|
26.7%
23/86 • Up to 6 months
|
31.8%
27/85 • Up to 6 months
|
|
Infections and infestations
Clostridial infection
|
5.8%
5/86 • Up to 6 months
|
5.9%
5/85 • Up to 6 months
|
|
Infections and infestations
Cytomegalovirus infection
|
18.6%
16/86 • Up to 6 months
|
16.5%
14/85 • Up to 6 months
|
|
Infections and infestations
Enterobacter infection
|
14.0%
12/86 • Up to 6 months
|
10.6%
9/85 • Up to 6 months
|
|
Infections and infestations
Enterococcal infection
|
32.6%
28/86 • Up to 6 months
|
43.5%
37/85 • Up to 6 months
|
|
Infections and infestations
Epstein-Barr virus infection
|
2.3%
2/86 • Up to 6 months
|
8.2%
7/85 • Up to 6 months
|
|
Infections and infestations
Escherichia infection
|
31.4%
27/86 • Up to 6 months
|
22.4%
19/85 • Up to 6 months
|
|
Infections and infestations
Haemophilus infection
|
1.2%
1/86 • Up to 6 months
|
5.9%
5/85 • Up to 6 months
|
|
Infections and infestations
Herpes simplex
|
3.5%
3/86 • Up to 6 months
|
7.1%
6/85 • Up to 6 months
|
|
Infections and infestations
Infection
|
4.7%
4/86 • Up to 6 months
|
9.4%
8/85 • Up to 6 months
|
|
Infections and infestations
Pneumonia klebsiella
|
10.5%
9/86 • Up to 6 months
|
18.8%
16/85 • Up to 6 months
|
|
Infections and infestations
Pseudomonas infection
|
9.3%
8/86 • Up to 6 months
|
10.6%
9/85 • Up to 6 months
|
|
Infections and infestations
Staphylococcal infection
|
39.5%
34/86 • Up to 6 months
|
38.8%
33/85 • Up to 6 months
|
|
Infections and infestations
Streptococcal infection
|
9.3%
8/86 • Up to 6 months
|
10.6%
9/85 • Up to 6 months
|
|
Injury, poisoning and procedural complications
Biliary anastomosis complication
|
10.5%
9/86 • Up to 6 months
|
8.2%
7/85 • Up to 6 months
|
|
Injury, poisoning and procedural complications
Procedural pain
|
25.6%
22/86 • Up to 6 months
|
38.8%
33/85 • Up to 6 months
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
9.3%
8/86 • Up to 6 months
|
17.6%
15/85 • Up to 6 months
|
|
Metabolism and nutrition disorders
Fluid retention
|
9.3%
8/86 • Up to 6 months
|
9.4%
8/85 • Up to 6 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
5.8%
5/86 • Up to 6 months
|
11.8%
10/85 • Up to 6 months
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
15.1%
13/86 • Up to 6 months
|
9.4%
8/85 • Up to 6 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
9.3%
8/86 • Up to 6 months
|
7.1%
6/85 • Up to 6 months
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
5.8%
5/86 • Up to 6 months
|
3.5%
3/85 • Up to 6 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
18.6%
16/86 • Up to 6 months
|
30.6%
26/85 • Up to 6 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.1%
7/86 • Up to 6 months
|
10.6%
9/85 • Up to 6 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.3%
2/86 • Up to 6 months
|
5.9%
5/85 • Up to 6 months
|
|
Nervous system disorders
Dizziness
|
9.3%
8/86 • Up to 6 months
|
14.1%
12/85 • Up to 6 months
|
|
Nervous system disorders
Headache
|
30.2%
26/86 • Up to 6 months
|
27.1%
23/85 • Up to 6 months
|
|
Nervous system disorders
Paraesthesia
|
15.1%
13/86 • Up to 6 months
|
8.2%
7/85 • Up to 6 months
|
|
Nervous system disorders
Somnolence
|
5.8%
5/86 • Up to 6 months
|
1.2%
1/85 • Up to 6 months
|
|
Nervous system disorders
Tremor
|
14.0%
12/86 • Up to 6 months
|
21.2%
18/85 • Up to 6 months
|
|
Psychiatric disorders
Anxiety
|
8.1%
7/86 • Up to 6 months
|
5.9%
5/85 • Up to 6 months
|
|
Psychiatric disorders
Delirium
|
10.5%
9/86 • Up to 6 months
|
5.9%
5/85 • Up to 6 months
|
|
Psychiatric disorders
Insomnia
|
34.9%
30/86 • Up to 6 months
|
54.1%
46/85 • Up to 6 months
|
|
Psychiatric disorders
Restlessness
|
11.6%
10/86 • Up to 6 months
|
17.6%
15/85 • Up to 6 months
|
|
Renal and urinary disorders
Nephropathy toxic
|
22.1%
19/86 • Up to 6 months
|
28.2%
24/85 • Up to 6 months
|
|
Renal and urinary disorders
Oliguria
|
5.8%
5/86 • Up to 6 months
|
8.2%
7/85 • Up to 6 months
|
|
Renal and urinary disorders
Polyuria
|
18.6%
16/86 • Up to 6 months
|
11.8%
10/85 • Up to 6 months
|
|
Renal and urinary disorders
Renal failure
|
5.8%
5/86 • Up to 6 months
|
4.7%
4/85 • Up to 6 months
|
|
Renal and urinary disorders
Renal impairment
|
8.1%
7/86 • Up to 6 months
|
14.1%
12/85 • Up to 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
9.3%
8/86 • Up to 6 months
|
4.7%
4/85 • Up to 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.0%
6/86 • Up to 6 months
|
3.5%
3/85 • Up to 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
22.1%
19/86 • Up to 6 months
|
18.8%
16/85 • Up to 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.0%
6/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
27.9%
24/86 • Up to 6 months
|
24.7%
21/85 • Up to 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
5.8%
5/86 • Up to 6 months
|
0.00%
0/85 • Up to 6 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.5%
9/86 • Up to 6 months
|
14.1%
12/85 • Up to 6 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.0%
6/86 • Up to 6 months
|
5.9%
5/85 • Up to 6 months
|
|
Vascular disorders
Hypertension
|
38.4%
33/86 • Up to 6 months
|
24.7%
21/85 • Up to 6 months
|
|
Vascular disorders
Hypotension
|
8.1%
7/86 • Up to 6 months
|
7.1%
6/85 • Up to 6 months
|
|
Vascular disorders
Intra-abdominal haemorrhage
|
3.5%
3/86 • Up to 6 months
|
7.1%
6/85 • Up to 6 months
|
Additional Information
Study Director
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