Cyclosporine A C-2h Monitoring Versus Tacrolimus C-0h Monitoring in de Novo Liver Transplant Recipients

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00149994
• Collaborator: (none)
• Enrollment: 171
• Location: 1
• Arms: 2
• Duration (Months): 60
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether cyclosporine A (in a micro emulsion formulation) monitored by sample taken 2 hour after oral dose (C-2h) will show equivalent or superior efficacy compared to tacrolimus monitored by pre-dose blood concentration (C-0h). In addition this study will assess the safety and tolerability of a cyclosporine A regimen based on C-2h monitoring in comparison to the standard tacrolimus regimen.

Condition or Disease	Intervention/Treatment	Phase
Liver Transplant	Drug: Cyclosporine A; Drug: Tacrolimus; Drug: Basiliximab; Drug: Methylprednisolone; Drug: Prednisone	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 171 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: DELTA Study Dutch Evaluation in Liver Transplantation To Assess the Efficacy of Cyclosporine A Microemulsion With C-2h Monitoring Versus Tacrolimus With Trough Monitoring in de Novo Liver Transplant Recipients
• Study Start Date: Dec 1, 2002
• Actual Primary Completion Date: Dec 1, 2007
• Actual Study Completion Date: Dec 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cyclosporine A Cyclosporine A was given in a twice-daily schedule 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, as close as possible to 15mg/kg/day. After the first oral administration, the dose of Cyclosporine A was adjusted to bring the sample taken 2 hours after oral dose (C-2h) level into the target range by Days 3-5 post-transplantation. C-2h target ranges post-transplantation: 0-3 months: range of 800-1200 ng/ml with midpoint of 1000 ng/ml; 4-6 months: range of 700-900 ng/ml with midpoint of 800 ng/ml; > 6 months: range of 500-700 ng/ml with midpoint of 600 ng/ml is recommended. During the course of the study, the dose of Cyclosporine A was adjusted as necessary to achieve and maintain the C-2h blood Cyclosporine A (CsA) concentrations within the target ranges.	Drug: Cyclosporine A; Drug: Basiliximab; Each patient was given two 20mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery.; Drug: Methylprednisolone; Methylprednisolone was given as an intravenous bolus of 500mg during transplant surgery; Drug: Prednisone; Post-operatively prednisone was tapered from an initial dose of 20mg/day to zero at 3 months or continued at 5-10mg if the indication for Orthotopic Liver Transplantation (OLTx) was of auto-immune nature.
Active Comparator: Tacrolimus Tacrolimus was given on a twice-daily schedule at 12-hour intervals which had to be maintained throughout the study period. Tacrolimus was administered within the first 24 hrs postoperatively (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 patient can swallow. The initial dosing level was determined by the patient's overall post-operative condition. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the pre-dose blood concentration (C-0h) (trough) tacrolimus concentrations. C-0h target ranges post-transplantation: 0-3 months: 10-15 ng/ml; 4-6 months: 5-10 ng/ml; > 6 months: range of 5-10 ng/ml is recommended.	Drug: Tacrolimus; Drug: Basiliximab; Each patient was given two 20mg doses of Basiliximab as intravenous bolus injection at Day 0 and Day 4 post-transplant surgery.; Drug: Methylprednisolone; Methylprednisolone was given as an intravenous bolus of 500mg during transplant surgery; Drug: Prednisone; Post-operatively prednisone was tapered from an initial dose of 20mg/day to zero at 3 months or continued at 5-10mg if the indication for Orthotopic Liver Transplantation (OLTx) was of auto-immune nature.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With an Occurrence of Biopsy Proven Acute Rejection (BPAR) During the First 3 Months Post de Novo Liver Transplantation. [Month 3]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All

Inclusion Criteria:

• About to undergo a primary liver transplant (including living donor, non-heart beating donor and split liver).

• Age between 18 and 75 years.

• Expected to be able to receive the first oral dose of CNI within the first 24 hours post-transplantation (Tx)

Exclusion Criteria:

• This is a multi-organ transplant or if the patient has previously been transplanted with any other organ.

• Urine production is <200 ml within 12 hours after reperfusion of the graft

• Severe coexisting disease is present or if any unstable medical condition is present which could affect the study objectives.

Other protocol-defined exclusion criteria applied

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis	Basel		Switzerland

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis, Novartis

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00149994
• Other Study ID Numbers: COLO400ANL07
• First Posted: Sep 8, 2005
• Last Update Posted: Apr 12, 2011
• Last Verified: Apr 1, 2011

• Keywords provided by , ,: Liver transplant, adults, C2 monitoring
• Additional relevant MeSH terms: Cyclosporine; Prednisone; Methylprednisolone; Tacrolimus; Cyclosporins; Basiliximab

Study Results

Participant Flow

Arm/Group Title	Cyclosporine A	Tacrolimus
Arm/Group Description	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 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.
Period Title: Overall Study
STARTED	85	86
COMPLETED	84	85
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Cyclosporine A	Tacrolimus	Total
Arm/Group Description	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 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 of all reporting groups
Overall Participants	84	85	169
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	48.1 (12.069)	49.9 (9.886)	48.98 (11.029)
Sex: Female, Male (Count of Participants)
Female	31 36.9%	30 35.3%	61 36.1%
Male	53 63.1%	55 64.7%	108 63.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With an Occurrence of Biopsy Proven Acute Rejection (BPAR) During the First 3 Months Post de Novo Liver Transplantation.
Description	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.
Time Frame	Month 3

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population.

Arm/Group Title	Cyclosporine A	Tacrolimus
Arm/Group Description	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 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.
Measure Participants	84	85
Number [Percentage of Participants]	33.3 39.6%	32.9 38.7%

Adverse Events

Time Frame	Up to 6 months
Arm/Group Title	Tacrolimus		Cyclosporine A
Arm/Group Description	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 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.
All Cause Mortality
	Tacrolimus		Cyclosporine A
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Tacrolimus		Cyclosporine A
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/86 (48.8%)		33/85 (38.8%)
Blood and lymphatic system disorders
Pancytopenia	0/86 (0%)		1/85 (1.2%)
Cardiac disorders
Arrhythmia	1/86 (1.2%)		0/85 (0%)
Cardiac arrest	1/86 (1.2%)		0/85 (0%)
Myocardial infarction	1/86 (1.2%)		0/85 (0%)
Gastrointestinal disorders
Abdominal pain	1/86 (1.2%)		0/85 (0%)
Abdominal pain upper	1/86 (1.2%)		1/85 (1.2%)
Ascites	0/86 (0%)		2/85 (2.4%)
Constipation	0/86 (0%)		1/85 (1.2%)
Crohn's disease	0/86 (0%)		1/85 (1.2%)
Diarrhoea	0/86 (0%)		2/85 (2.4%)
Gastric haemorrhage	0/86 (0%)		1/85 (1.2%)
Gastrointestinal necrosis	1/86 (1.2%)		0/85 (0%)
Megacolon	1/86 (1.2%)		0/85 (0%)
Nausea	2/86 (2.3%)		0/85 (0%)
Pancreatitis	0/86 (0%)		1/85 (1.2%)
Truncus coeliacus thrombosis	1/86 (1.2%)		0/85 (0%)
Umbilical hernia	0/86 (0%)		1/85 (1.2%)
Vomiting	3/86 (3.5%)		0/85 (0%)
General disorders
Chest pain	0/86 (0%)		1/85 (1.2%)
Chills	1/86 (1.2%)		0/85 (0%)
Malaise	0/86 (0%)		1/85 (1.2%)
Pain	0/86 (0%)		1/85 (1.2%)
Pyrexia	11/86 (12.8%)		4/85 (4.7%)
Hepatobiliary disorders
Biliary dilatation	0/86 (0%)		1/85 (1.2%)
Biliary ischaemia	0/86 (0%)		1/85 (1.2%)
Biloma	2/86 (2.3%)		0/85 (0%)
Cholangitis	3/86 (3.5%)		2/85 (2.4%)
Cholestasis	0/86 (0%)		2/85 (2.4%)
Hepatic artery thrombosis	1/86 (1.2%)		1/85 (1.2%)
Hepatic failure	1/86 (1.2%)		0/85 (0%)
Hepatic haemorrhage	1/86 (1.2%)		0/85 (0%)
Hepatic necrosis	0/86 (0%)		1/85 (1.2%)
Jaundice	1/86 (1.2%)		1/85 (1.2%)
Liver function test abnormal	1/86 (1.2%)		0/85 (0%)
Liver injury	0/86 (0%)		1/85 (1.2%)
Portal vein thrombosis	2/86 (2.3%)		0/85 (0%)
Immune system disorders
Graft versus host disease	1/86 (1.2%)		0/85 (0%)
Infections and infestations
Bacteraemia	0/86 (0%)		1/85 (1.2%)
Cytomegalovirus colitis	0/86 (0%)		1/85 (1.2%)
Cytomegalovirus infection	2/86 (2.3%)		0/85 (0%)
Hepatitis C	0/86 (0%)		1/85 (1.2%)
Liver abscess	1/86 (1.2%)		0/85 (0%)
Pneumonia	1/86 (1.2%)		0/85 (0%)
Sepsis	2/86 (2.3%)		1/85 (1.2%)
Septic shock	1/86 (1.2%)		1/85 (1.2%)
Urinary tract infection	1/86 (1.2%)		0/85 (0%)
Injury, poisoning and procedural complications
Biliary anastomosis complication	3/86 (3.5%)		3/85 (3.5%)
Hepatic haematoma	1/86 (1.2%)		0/85 (0%)
Post procedural haemorrhage	0/86 (0%)		1/85 (1.2%)
Transplant failure	0/86 (0%)		1/85 (1.2%)
Investigations
Hepatic enzyme increased	0/86 (0%)		1/85 (1.2%)
Transaminases increased	2/86 (2.3%)		1/85 (1.2%)
Metabolism and nutrition disorders
Dehydration	1/86 (1.2%)		0/85 (0%)
Diabetes mellitus	0/86 (0%)		1/85 (1.2%)
Hyperglycaemia	0/86 (0%)		2/85 (2.4%)
Hyperkalaemia	1/86 (1.2%)		0/85 (0%)
Ketoacidosis	0/86 (0%)		1/85 (1.2%)
Musculoskeletal and connective tissue disorders
Back pain	2/86 (2.3%)		2/85 (2.4%)
Compartment syndrome	1/86 (1.2%)		0/85 (0%)
Musculoskeletal pain	1/86 (1.2%)		0/85 (0%)
Nervous system disorders
Amnesia	0/86 (0%)		1/85 (1.2%)
Cerebral haemorrhage	1/86 (1.2%)		0/85 (0%)
Convulsion	1/86 (1.2%)		0/85 (0%)
Epilepsy	0/86 (0%)		1/85 (1.2%)
Neurotoxicity	1/86 (1.2%)		0/85 (0%)
Psychiatric disorders
Completed suicide	1/86 (1.2%)		0/85 (0%)
Renal and urinary disorders
Nephropathy toxic	0/86 (0%)		2/85 (2.4%)
Oliguria	0/86 (0%)		1/85 (1.2%)
Renal failure	1/86 (1.2%)		1/85 (1.2%)
Renal impairment	1/86 (1.2%)		0/85 (0%)
Respiratory, thoracic and mediastinal disorders
Brain hypoxia	0/86 (0%)		1/85 (1.2%)
Cough	0/86 (0%)		1/85 (1.2%)
Dyspnoea	1/86 (1.2%)		2/85 (2.4%)
Interstitial lung disease	0/86 (0%)		1/85 (1.2%)
Pleural effusion	1/86 (1.2%)		1/85 (1.2%)
Pneumonia aspiration	2/86 (2.3%)		0/85 (0%)
Respiratory failure	1/86 (1.2%)		1/85 (1.2%)
Stridor	1/86 (1.2%)		0/85 (0%)
Skin and subcutaneous tissue disorders
Dermatitis herpetiformis	1/86 (1.2%)		0/85 (0%)
Pruritus	1/86 (1.2%)		0/85 (0%)
Rash	1/86 (1.2%)		0/85 (0%)
Vascular disorders
Arterial haemorrhage	0/86 (0%)		1/85 (1.2%)
Deep vein thrombosis	0/86 (0%)		1/85 (1.2%)
Hypovolaemic shock	0/86 (0%)		1/85 (1.2%)
Intra-abdominal haemorrhage	0/86 (0%)		1/85 (1.2%)
Shock haemorrhagic	1/86 (1.2%)		1/85 (1.2%)
Other (Not Including Serious) Adverse Events
	Tacrolimus		Cyclosporine A
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	84/86 (97.7%)		85/85 (100%)
Blood and lymphatic system disorders
Anaemia	20/86 (23.3%)		28/85 (32.9%)
Thrombocytopenia	5/86 (5.8%)		7/85 (8.2%)
Cardiac disorders
Cardiac failure	5/86 (5.8%)		4/85 (4.7%)
Tachycardia	5/86 (5.8%)		7/85 (8.2%)
Gastrointestinal disorders
Abdominal pain	14/86 (16.3%)		24/85 (28.2%)
Abdominal pain upper	10/86 (11.6%)		9/85 (10.6%)
Ascites	29/86 (33.7%)		35/85 (41.2%)
Constipation	26/86 (30.2%)		32/85 (37.6%)
Diarrhoea	26/86 (30.2%)		54/85 (63.5%)
Dyspepsia	4/86 (4.7%)		5/85 (5.9%)
Ileus	6/86 (7%)		2/85 (2.4%)
Impaired gastric emptying	2/86 (2.3%)		7/85 (8.2%)
Nausea	40/86 (46.5%)		39/85 (45.9%)
Vomiting	25/86 (29.1%)		26/85 (30.6%)
General disorders
Chest pain	7/86 (8.1%)		3/85 (3.5%)
Fatigue	8/86 (9.3%)		12/85 (14.1%)
Oedema	41/86 (47.7%)		37/85 (43.5%)
Pain	8/86 (9.3%)		10/85 (11.8%)
Pyrexia	25/86 (29.1%)		33/85 (38.8%)
Hepatobiliary disorders
Biloma	5/86 (5.8%)		1/85 (1.2%)
Cholestasis	4/86 (4.7%)		8/85 (9.4%)
Jaundice	6/86 (7%)		0/85 (0%)
Infections and infestations
- Unknown Infections -	23/86 (26.7%)		18/85 (21.2%)
Candidiasis	23/86 (26.7%)		27/85 (31.8%)
Clostridial infection	5/86 (5.8%)		5/85 (5.9%)
Cytomegalovirus infection	16/86 (18.6%)		14/85 (16.5%)
Enterobacter infection	12/86 (14%)		9/85 (10.6%)
Enterococcal infection	28/86 (32.6%)		37/85 (43.5%)
Epstein-Barr virus infection	2/86 (2.3%)		7/85 (8.2%)
Escherichia infection	27/86 (31.4%)		19/85 (22.4%)
Haemophilus infection	1/86 (1.2%)		5/85 (5.9%)
Herpes simplex	3/86 (3.5%)		6/85 (7.1%)
Infection	4/86 (4.7%)		8/85 (9.4%)
Pneumonia klebsiella	9/86 (10.5%)		16/85 (18.8%)
Pseudomonas infection	8/86 (9.3%)		9/85 (10.6%)
Staphylococcal infection	34/86 (39.5%)		33/85 (38.8%)
Streptococcal infection	8/86 (9.3%)		9/85 (10.6%)
Injury, poisoning and procedural complications
Biliary anastomosis complication	9/86 (10.5%)		7/85 (8.2%)
Procedural pain	22/86 (25.6%)		33/85 (38.8%)
Metabolism and nutrition disorders
Diabetes mellitus	8/86 (9.3%)		15/85 (17.6%)
Fluid retention	8/86 (9.3%)		8/85 (9.4%)
Hyperglycaemia	5/86 (5.8%)		10/85 (11.8%)
Hyperkalaemia	13/86 (15.1%)		8/85 (9.4%)
Hypokalaemia	8/86 (9.3%)		6/85 (7.1%)
Hypomagnesaemia	5/86 (5.8%)		3/85 (3.5%)
Musculoskeletal and connective tissue disorders
Back pain	16/86 (18.6%)		26/85 (30.6%)
Myalgia	7/86 (8.1%)		9/85 (10.6%)
Pain in extremity	2/86 (2.3%)		5/85 (5.9%)
Nervous system disorders
Dizziness	8/86 (9.3%)		12/85 (14.1%)
Headache	26/86 (30.2%)		23/85 (27.1%)
Paraesthesia	13/86 (15.1%)		7/85 (8.2%)
Somnolence	5/86 (5.8%)		1/85 (1.2%)
Tremor	12/86 (14%)		18/85 (21.2%)
Psychiatric disorders
Anxiety	7/86 (8.1%)		5/85 (5.9%)
Delirium	9/86 (10.5%)		5/85 (5.9%)
Insomnia	30/86 (34.9%)		46/85 (54.1%)
Restlessness	10/86 (11.6%)		15/85 (17.6%)
Renal and urinary disorders
Nephropathy toxic	19/86 (22.1%)		24/85 (28.2%)
Oliguria	5/86 (5.8%)		7/85 (8.2%)
Polyuria	16/86 (18.6%)		10/85 (11.8%)
Renal failure	5/86 (5.8%)		4/85 (4.7%)
Renal impairment	7/86 (8.1%)		12/85 (14.1%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	8/86 (9.3%)		4/85 (4.7%)
Cough	6/86 (7%)		3/85 (3.5%)
Dyspnoea	19/86 (22.1%)		16/85 (18.8%)
Oropharyngeal pain	6/86 (7%)		0/85 (0%)
Pleural effusion	24/86 (27.9%)		21/85 (24.7%)
Respiratory failure	5/86 (5.8%)		0/85 (0%)
Skin and subcutaneous tissue disorders
Pruritus	9/86 (10.5%)		12/85 (14.1%)
Rash	6/86 (7%)		5/85 (5.9%)
Vascular disorders
Hypertension	33/86 (38.4%)		21/85 (24.7%)
Hypotension	7/86 (8.1%)		6/85 (7.1%)
Intra-abdominal haemorrhage	3/86 (3.5%)		6/85 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.