Efficacy and Safety of Basiliximab, Cyclosporine/Cyclosporine Microemulsion, and Steroids in Pediatric de Novo Liver Transplant Recipients Avoiding Intraoperative Steroids

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00149890
• Collaborator: (none)
• Enrollment: 77
• Location: 1
• Arms: 2
• Duration (Months): 60
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

Systemic infection is still a major concern in young children with liver transplantation. The approach of this study is to reduce the risk of systemic infections by avoiding intraoperative steroids (another class of immunosuppressive drugs) given in combination with basiliximab, cyclosporine and steroids in pediatric de novo liver transplant recipients. The treatment is compared to the same treatment regimen including intraoperative steroids with respect to rejection episodes.

Condition or Disease	Intervention/Treatment	Phase
Liver Transplantation; Infection	Drug: Basiliximab; Drug: Cyclosporine/cyclosporine microemulsion; Drug: Steroid	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 77 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Multicenter, Open-label, Randomized, Two Arm Study to Investigate the Efficacy and Safety of a Therapy Avoiding Intraoperative Steroids in Combination With Basiliximab, Cyclosporine/Cyclosporine Microemulsion, and Steroids in Pediatric de Novo Liver Transplant Recipients
• Study Start Date: Mar 1, 2004
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: With Intraoperative Steroids Intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab was administered as an intravenous bolus injection within 8 hours after reperfusion of the graft.	Drug: Basiliximab; Basiliximab (10 mg) was supplied as a lyophilisate in vials with ampoules of sterile water for injection (5 mL) and had to be given of 10 mg (body weight <35 kg) or 20 mg (body weight ≥35 kg) strength.; Other Names: Simulect® ; Drug: Cyclosporine/cyclosporine microemulsion; Cyclosporine/cyclosporine microemulsion had to be started with 100 mg/m²/day intravenous (i.v) (2x4h) for 7 days and was to be continued i.v. or orally from day 8 onwards as per center practice. During the 6 months treatment period Cyclosporine doses had to be adjusted according to Cyclosporine A (CsA)-trough levels.; Other Names: Sandimmun®/Sandimmun® Optoral ; Drug: Steroid; Intravenous prednisolone (loading dose: 300 mg/m2, maximum 500 mg) had to be administered intraoperatively only in treatment arm 1 (day 0). The first dose of steroids in treatment arm 2 (day 0) had to be administered within 8 hours after reperfusion of the graft. Beginning from day 1 to day 6 doses of 15 mg/m2/day had to be given intravenously (i.v.) in both treatment arms. Then, the steroid doses (oral prednisone or its equivalent) were to be decreased from 10 mg/m²/day orally (day 7-13), to 7.5 mg/m²/day orally (day 14-30), to 4 mg/m²/day orally (until end of month 2), to 2.5 mg/m²/day orally (until end of month 3) and to 1 mg/m²/day orally (until end of month 6).
Active Comparator: Without Intraoperative Steroids No intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab and the first dose of steroids had to be administered within 8 hours after reperfusion of the graft and basiliximab was given as an intravenous bolus injection.	Drug: Basiliximab; Basiliximab (10 mg) was supplied as a lyophilisate in vials with ampoules of sterile water for injection (5 mL) and had to be given of 10 mg (body weight <35 kg) or 20 mg (body weight ≥35 kg) strength.; Other Names: Simulect® ; Drug: Cyclosporine/cyclosporine microemulsion; Cyclosporine/cyclosporine microemulsion had to be started with 100 mg/m²/day intravenous (i.v) (2x4h) for 7 days and was to be continued i.v. or orally from day 8 onwards as per center practice. During the 6 months treatment period Cyclosporine doses had to be adjusted according to Cyclosporine A (CsA)-trough levels.; Other Names: Sandimmun®/Sandimmun® Optoral ; Drug: Steroid; Intravenous prednisolone (loading dose: 300 mg/m2, maximum 500 mg) had to be administered intraoperatively only in treatment arm 1 (day 0). The first dose of steroids in treatment arm 2 (day 0) had to be administered within 8 hours after reperfusion of the graft. Beginning from day 1 to day 6 doses of 15 mg/m2/day had to be given intravenously (i.v.) in both treatment arms. Then, the steroid doses (oral prednisone or its equivalent) were to be decreased from 10 mg/m²/day orally (day 7-13), to 7.5 mg/m²/day orally (day 14-30), to 4 mg/m²/day orally (until end of month 2), to 2.5 mg/m²/day orally (until end of month 3) and to 1 mg/m²/day orally (until end of month 6).

Outcome Measures

Primary Outcome Measures

1. Number of Participants With at Least One Biopsy Proven Acute Rejection (BPAR) Episode, Graft Loss or Death Within the First Three Months Post-transplantation [3 months after treatment]

   Graft loss is defined as being listed for a re-transplantation. The analysis was based on the locally performed biopsy assessments. Generally, patients not experiencing a relevant event (i.e., acute rejection, graft loss or death) were censored with the last visit date.

Secondary Outcome Measures

1. Number of Participants With Biopsy Proven Acute Rejection (BPAR) Episodes Within the First Three Months [3 months]

   At biopsy of transplanted tissue sample, acute rejection has an onset 2-60 days after transplantation, with interstitial vascular endothelial cell swelling, interstitial accumulation of lymphocytes, plasma cells, immunoblasts, macrophages, neutrophils; tubular separation with edema/necrosis of tubular epithelium; swelling and vacuolization of the endothelial cells, vascular edema, bleeding and inflammation. Clinical signs and symptoms include malaise, fever, and hypertension.

2. Number of Participants With Steroid Resistant Rejection Episodes Within Three and Six Months [3 and 6 months]

   To evaluate the efficacy of a regimen with intraoperative versus without intraoperative steroids in combination with basiliximab, cyclosporine/cyclosporine microemulsion and steroids as measured by the incidence of steroid resistant rejection episodes within three and six months.

3. Percentage of Participants Experiencing Death or Graft Loss Within Three and Six Months After Transplantation [3 months and 6 months]

   Graft loss is defined as being listed for a re-transplantation.

4. Number of Participants With Bacterial, Viral and Fungal Infections During Six Months [6 months]

   To evaluate the safety of a regimen with intraoperative versus without intraoperative steroids in combination with basiliximab, cyclosporine/cyclosporine microemulsion and steroids as measured by the episodes of bacterial, viral and fungal infections during six months.

5. Time of Onset of a First Biopsy Proven Acute Rejection [6 months]

   Biopsied Tissue shows rejection at onset 2-60 days after transplantation, with interstitial vascular endothelial cell swelling, interstitial accumulation of lymphocytes, plasma cells, immunoblasts, macrophages, neutrophils; tubular separation with edema/necrosis of tubular epithelium; swelling and vacuolization of the endothelial cells, vascular edema, bleeding and inflammation. Clinical signs and symptoms include malaise, fever and hypertension .

6. Percentage of Participants With Treatment Failure Within Three and Six Months [3 and 6 months]

   To evaluate the proportion of patients with treatment failure treated with a therapy consisting of intraoperative versus without intraoperative steroids in combination with basiliximab, cyclosporine/cyclosporine microemulsion and steroids within three and six months.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 16 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Pediatric patients undergoing primary orthotopic liver transplantation (whole organ or split liver or reduced size)

• Cadaveric or living donor (related or unrelated)

Exclusion Criteria:

• Patients who are recipients of multiple solid organ transplants and/or who have previously received transplanted organs

• If cold ischemia time of the transplanted organ is >12 hours

• Auxiliary liver transplant recipients

• Fulminant hepatic failure

• Autoimmune hepatitis

• Primary sclerosing cholangitis

• Severe acute systemic infections

• Hepatitis B surface antigen/HCV/HIV positive

• Known contraindication to intravenous (i.v.) or per os (orally) (p.o.) cyclosporine or corticoids

• Non-ability to comply with the protocol

• Relevant abnormal physical or laboratory findings within 2 weeks of inclusion

• Relevant severe allergy, hypersensitivity to basiliximab or similar drugs

• History/presence of relevant malignancy

• Pregnancy/breastfeeding

• Use of any investigational or immunomodulatory/immunosuppressive drug within 4 weeks prior to transplantation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigational Site	Various Cities		Germany

Sponsors and Collaborators

• Novartis

Investigators

• Study Director: Novartis, Novartis

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00149890
• Other Study ID Numbers: CCHI621ADE04
• First Posted: Sep 8, 2005
• Last Update Posted: Sep 22, 2011
• Last Verified: Aug 1, 2011

• Keywords provided by , ,: pediatric; liver transplantation; Simulect; Basiliximab; ciclosporin microemulsion; steroid reduction; pediatric liver transplantation
• Additional relevant MeSH terms: Cyclosporine; Cyclosporins; Basiliximab

Study Results

Participant Flow

Arm/Group Title	With Intraoperative Steroids	Without Intraoperative Steroids
Arm/Group Description	Intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab was administered as an intravenous bolus injection within 8 hours after reperfusion of the graft.	No intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab and the first dose of steroids had to be administered within 8 hours after reperfusion of the graft and basiliximab was given as an intravenous bolus injection.
Period Title: Overall Study
STARTED	39	38
COMPLETED	26	20
NOT COMPLETED	13	18

Baseline Characteristics

Arm/Group Title	With Intraoperative Steroids	Without Intraoperative Steroids	Total
Arm/Group Description	Intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab was administered as an intravenous bolus injection within 8 hours after reperfusion of the graft.	No intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab and the first dose of steroids had to be administered within 8 hours after reperfusion of the graft and basiliximab was given as an intravenous bolus injection.	Total of all reporting groups
Overall Participants	39	38	77
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	3.08 (4.09)	3.71 (5.36)	3.39 (4.74)
Age, Customized (participants) [Number]
<2 years	21 53.8%	24 63.2%	45 58.4%
from 2 to 16 years	18 46.2%	14 36.8%	32 41.6%
Sex: Female, Male (Count of Participants)
Female	21 53.8%	19 50%	40 51.9%
Male	18 46.2%	19 50%	37 48.1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With at Least One Biopsy Proven Acute Rejection (BPAR) Episode, Graft Loss or Death Within the First Three Months Post-transplantation
Description	Graft loss is defined as being listed for a re-transplantation. The analysis was based on the locally performed biopsy assessments. Generally, patients not experiencing a relevant event (i.e., acute rejection, graft loss or death) were censored with the last visit date.
Time Frame	3 months after treatment

Outcome Measure Data

Analysis Population Description

safety/Intent to Treat (ITT) population

Arm/Group Title	With Intraoperative Steroids	Without Intraoperative Steroids
Arm/Group Description	Intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab was administered as an intravenous bolus injection within 8 hours after reperfusion of the graft.	No intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab and the first dose of steroids had to be administered within 8 hours after reperfusion of the graft and basiliximab was given as an intravenous bolus injection.
Measure Participants	39	38
Stratum age < 2 years (N=21, 24)	8 20.5%	15 39.5%
Stratum age 2-16 years (N=18, 14)	14 35.9%	11 28.9%
Total (N= 39, 38)	22 56.4%	26 68.4%

2. Secondary Outcome

Title	Number of Participants With Biopsy Proven Acute Rejection (BPAR) Episodes Within the First Three Months
Description	At biopsy of transplanted tissue sample, acute rejection has an onset 2-60 days after transplantation, with interstitial vascular endothelial cell swelling, interstitial accumulation of lymphocytes, plasma cells, immunoblasts, macrophages, neutrophils; tubular separation with edema/necrosis of tubular epithelium; swelling and vacuolization of the endothelial cells, vascular edema, bleeding and inflammation. Clinical signs and symptoms include malaise, fever, and hypertension.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

safety/Intent to Treat (ITT) population

Arm/Group Title	With Intraoperative Steroids	Without Intraoperative Steroids
Arm/Group Description	Intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab was administered as an intravenous bolus injection within 8 hours after reperfusion of the graft.	No intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab and the first dose of steroids had to be administered within 8 hours after reperfusion of the graft and basiliximab was given as an intravenous bolus injection.
Measure Participants	39	38
Number [Participants]	20 51.3%	26 68.4%

3. Secondary Outcome

Title	Number of Participants With Steroid Resistant Rejection Episodes Within Three and Six Months
Description	To evaluate the efficacy of a regimen with intraoperative versus without intraoperative steroids in combination with basiliximab, cyclosporine/cyclosporine microemulsion and steroids as measured by the incidence of steroid resistant rejection episodes within three and six months.
Time Frame	3 and 6 months

Outcome Measure Data

Analysis Population Description

safety/Intent to Treat (ITT) population

Arm/Group Title	With Intraoperative Steroids	Without Intraoperative Steroids
Arm/Group Description	Intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab was administered as an intravenous bolus injection within 8 hours after reperfusion of the graft.	No intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab and the first dose of steroids had to be administered within 8 hours after reperfusion of the graft and basiliximab was given as an intravenous bolus injection.
Measure Participants	39	38
Within 3 months post treatment	2 5.1%	2 5.3%
Within 6 months post treatment	2 5.1%	2 5.3%

4. Secondary Outcome

Title	Percentage of Participants Experiencing Death or Graft Loss Within Three and Six Months After Transplantation
Description	Graft loss is defined as being listed for a re-transplantation.
Time Frame	3 months and 6 months

Outcome Measure Data

Analysis Population Description

safety/Intent to Treat (ITT) population

Arm/Group Title	With Intraoperative Steroids	Without Intraoperative Steroids
Arm/Group Description	Intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab was administered as an intravenous bolus injection within 8 hours after reperfusion of the graft.	No intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab and the first dose of steroids had to be administered within 8 hours after reperfusion of the graft and basiliximab was given as an intravenous bolus injection.
Measure Participants	39	38
Death within 3 months post treatment	0.0 0%	2.6 6.8%
Death within 6 months post treatment	0.0 0%	2.6 6.8%
Graft Loss within 3 months post treatment	5.1 13.1%	2.6 6.8%
Graft Loss within 6 months post treatment	5.1 13.1%	5.3 13.9%

5. Secondary Outcome

Title	Number of Participants With Bacterial, Viral and Fungal Infections During Six Months
Description	To evaluate the safety of a regimen with intraoperative versus without intraoperative steroids in combination with basiliximab, cyclosporine/cyclosporine microemulsion and steroids as measured by the episodes of bacterial, viral and fungal infections during six months.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	With Intraoperative Steroids	Without Intraoperative Steroids
Arm/Group Description	Intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab was administered as an intravenous bolus injection within 8 hours after reperfusion of the graft.	No intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab and the first dose of steroids had to be administered within 8 hours after reperfusion of the graft and basiliximab was given as an intravenous bolus injection.
Measure Participants	39	38
Fungal	16 41%	16 42.1%
Viral	15 38.5%	14 36.8%
Bacterial	10 25.6%	18 47.4%

6. Secondary Outcome

Title	Time of Onset of a First Biopsy Proven Acute Rejection
Description	Biopsied Tissue shows rejection at onset 2-60 days after transplantation, with interstitial vascular endothelial cell swelling, interstitial accumulation of lymphocytes, plasma cells, immunoblasts, macrophages, neutrophils; tubular separation with edema/necrosis of tubular epithelium; swelling and vacuolization of the endothelial cells, vascular edema, bleeding and inflammation. Clinical signs and symptoms include malaise, fever and hypertension .
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

safety/Intent to Treat (ITT) population

Arm/Group Title	With Intraoperative Steroids	Without Intraoperative Steroids
Arm/Group Description	Intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab was administered as an intravenous bolus injection within 8 hours after reperfusion of the graft.	No intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab and the first dose of steroids had to be administered within 8 hours after reperfusion of the graft and basiliximab was given as an intravenous bolus injection.
Measure Participants	39	38
Median (95% Confidence Interval) [Months]	1.93	0.75

7. Secondary Outcome

Title	Percentage of Participants With Treatment Failure Within Three and Six Months
Description	To evaluate the proportion of patients with treatment failure treated with a therapy consisting of intraoperative versus without intraoperative steroids in combination with basiliximab, cyclosporine/cyclosporine microemulsion and steroids within three and six months.
Time Frame	3 and 6 months

Outcome Measure Data

Analysis Population Description

Intention to treat population

Arm/Group Title	With Intraoperative Steroids	Without Intraoperative Steroids
Arm/Group Description	Intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab was administered as an intravenous bolus injection within 8 hours after reperfusion of the graft.	No intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab and the first dose of steroids had to be administered within 8 hours after reperfusion of the graft and basiliximab was given as an intravenous bolus injection.
Measure Participants	39	38
3 month: Age < 2 years (N= 21, 24)	0.00 0%	4.17 11%
3 month: Age 2-16 years (N= 18, 14)	11.11 28.5%	7.14 18.8%
3 Month: Total	5.13 13.2%	5.26 13.8%
6 month: Age < 2 years (N= 21, 24)	0.00 0%	4.17 11%
6 month: Age 2-16 years (N= 18, 14)	11.11 28.5%	7.14 18.8%
6 Month: Total	5.13 13.2%	5.26 13.8%

Adverse Events

Time Frame	6 months
Arm/Group Title	With Intraoperative Steroids		Without Intraoperative Steroids
Arm/Group Description	Intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab was administered as an intravenous bolus injection within 8 hours after reperfusion of the graft.		No intraoperative steroids were administered during transplantation and Basiliximab was administered on Day 0 and 4 (10 mg if the body weight was <35 kg; 20 mg if body weight was ≥35 kg) in combination with cyclosporine/cyclosporine microemulsion and steroids. Basiliximab and the first dose of steroids had to be administered within 8 hours after reperfusion of the graft and basiliximab was given as an intravenous bolus injection.
All Cause Mortality
	With Intraoperative Steroids		Without Intraoperative Steroids
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	With Intraoperative Steroids		Without Intraoperative Steroids
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/39 (46.2%)		23/38 (60.5%)
Blood and lymphatic system disorders
Bone marrow failure	0/39 (0%)		1/38 (2.6%)
Haemolytic anaemia	0/39 (0%)		1/38 (2.6%)
Leukopenia	1/39 (2.6%)		1/38 (2.6%)
Thrombocytopenia	1/39 (2.6%)		0/38 (0%)
Cardiac disorders
Atrial flutter	0/39 (0%)		1/38 (2.6%)
Cardiac arrest	1/39 (2.6%)		0/38 (0%)
Cardiovascular insufficiency	0/39 (0%)		1/38 (2.6%)
Congenital, familial and genetic disorders
Hydrocele	1/39 (2.6%)		0/38 (0%)
Endocrine disorders
Adrenal insufficiency	0/39 (0%)		1/38 (2.6%)
Gastrointestinal disorders
Abdominal distension	1/39 (2.6%)		0/38 (0%)
Abdominal pain	1/39 (2.6%)		0/38 (0%)
Ascites	0/39 (0%)		1/38 (2.6%)
Coeliac disease	1/39 (2.6%)		0/38 (0%)
Enteritis	0/39 (0%)		1/38 (2.6%)
Gastric ulcer haemorrhage	0/39 (0%)		1/38 (2.6%)
Ileal fistula	0/39 (0%)		1/38 (2.6%)
Ileus	0/39 (0%)		1/38 (2.6%)
Inguinal hernia, obstructive	1/39 (2.6%)		0/38 (0%)
Large intestine perforation	0/39 (0%)		1/38 (2.6%)
Oesophageal varices haemorrhage	1/39 (2.6%)		0/38 (0%)
Peritonitis	2/39 (5.1%)		1/38 (2.6%)
Small intestinal perforation	2/39 (5.1%)		1/38 (2.6%)
General disorders
Device occlusion	0/39 (0%)		1/38 (2.6%)
Disease progression	0/39 (0%)		1/38 (2.6%)
Obstruction	0/39 (0%)		1/38 (2.6%)
Pain	1/39 (2.6%)		0/38 (0%)
Pyrexia	2/39 (5.1%)		1/38 (2.6%)
Hepatobiliary disorders
Bile duct stenosis	0/39 (0%)		1/38 (2.6%)
Biliary dilatation	0/39 (0%)		2/38 (5.3%)
Biloma	0/39 (0%)		2/38 (5.3%)
Cholangitis	2/39 (5.1%)		2/38 (5.3%)
Cholestasis	2/39 (5.1%)		0/38 (0%)
Chronic hepatic failure	0/39 (0%)		1/38 (2.6%)
Haemobilia	1/39 (2.6%)		0/38 (0%)
Hepatic artery thrombosis	0/39 (0%)		1/38 (2.6%)
Hepatic necrosis	2/39 (5.1%)		0/38 (0%)
Hepatic vein thrombosis	1/39 (2.6%)		0/38 (0%)
Liver disorder	0/39 (0%)		1/38 (2.6%)
Portal vein stenosis	1/39 (2.6%)		0/38 (0%)
Portal vein thrombosis	0/39 (0%)		1/38 (2.6%)
Immune system disorders
Hypersensitivity	0/39 (0%)		1/38 (2.6%)
Infections and infestations
Bacteraemia	0/39 (0%)		1/38 (2.6%)
Biliary tract infection	0/39 (0%)		1/38 (2.6%)
Cytomegalovirus infection	5/39 (12.8%)		0/38 (0%)
Device related sepsis	0/39 (0%)		1/38 (2.6%)
Enterococcal infection	0/39 (0%)		1/38 (2.6%)
Epstein-barr viraemia	1/39 (2.6%)		0/38 (0%)
Escherichia sepsis	0/39 (0%)		1/38 (2.6%)
Gastroenteritis	2/39 (5.1%)		3/38 (7.9%)
Gastroenteritis astroviral	0/39 (0%)		1/38 (2.6%)
Gastroenteritis norovirus	0/39 (0%)		2/38 (5.3%)
Pneumonia	0/39 (0%)		1/38 (2.6%)
Sepsis	0/39 (0%)		1/38 (2.6%)
Upper respiratory tract infection	1/39 (2.6%)		0/38 (0%)
Injury, poisoning and procedural complications
Anastomotic haemorrhage	0/39 (0%)		1/38 (2.6%)
Arterial injury	0/39 (0%)		1/38 (2.6%)
Biliary anastomosis complication	1/39 (2.6%)		1/38 (2.6%)
Complications of transplanted liver	3/39 (7.7%)		2/38 (5.3%)
Gastrointestinal anastomotic leak	0/39 (0%)		2/38 (5.3%)
Graft complication	0/39 (0%)		1/38 (2.6%)
Hepatic haematoma	0/39 (0%)		1/38 (2.6%)
Hepatic rupture	1/39 (2.6%)		0/38 (0%)
Incisional hernia	1/39 (2.6%)		0/38 (0%)
Post procedural bile leak	0/39 (0%)		5/38 (13.2%)
Post procedural complication	0/39 (0%)		1/38 (2.6%)
Investigations
Epstein-barr virus antibody positive	1/39 (2.6%)		0/38 (0%)
Hepatic enzyme increased	2/39 (5.1%)		0/38 (0%)
Immunosuppressant drug level decreased	1/39 (2.6%)		0/38 (0%)
Transaminases increased	2/39 (5.1%)		1/38 (2.6%)
Metabolism and nutrition disorders
Dehydration	1/39 (2.6%)		1/38 (2.6%)
Hyperkalaemia	2/39 (5.1%)		0/38 (0%)
Hyponatraemia	1/39 (2.6%)		1/38 (2.6%)
Hypoproteinaemia	0/39 (0%)		1/38 (2.6%)
Metabolic acidosis	1/39 (2.6%)		1/38 (2.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Histiocytosis haematophagic	0/39 (0%)		1/38 (2.6%)
Renal and urinary disorders
Renal failure	0/39 (0%)		1/38 (2.6%)
Renal impairment	1/39 (2.6%)		0/38 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	0/39 (0%)		1/38 (2.6%)
Bronchomalacia	0/39 (0%)		1/38 (2.6%)
Chylothorax	0/39 (0%)		1/38 (2.6%)
Diaphragmatic rupture	0/39 (0%)		1/38 (2.6%)
Hepatopulmonary syndrome	0/39 (0%)		1/38 (2.6%)
Obstructive airways disorder	1/39 (2.6%)		0/38 (0%)
Pleural effusion	0/39 (0%)		2/38 (5.3%)
Pulmonary haemorrhage	0/39 (0%)		1/38 (2.6%)
Respiratory failure	0/39 (0%)		2/38 (5.3%)
Tachypnoea	0/39 (0%)		1/38 (2.6%)
Tracheal stenosis	0/39 (0%)		1/38 (2.6%)
Skin and subcutaneous tissue disorders
Rash	0/39 (0%)		1/38 (2.6%)
Urticaria	0/39 (0%)		1/38 (2.6%)
Vascular disorders
Haemorrhage	0/39 (0%)		1/38 (2.6%)
Hypotension	0/39 (0%)		1/38 (2.6%)
Inferior vena caval occlusion	0/39 (0%)		1/38 (2.6%)
Intra-abdominal haematoma	1/39 (2.6%)		0/38 (0%)
Intra-abdominal haemorrhage	1/39 (2.6%)		0/38 (0%)
Reperfusion injury	2/39 (5.1%)		0/38 (0%)
Other (Not Including Serious) Adverse Events
	With Intraoperative Steroids		Without Intraoperative Steroids
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/39 (100%)		38/38 (100%)
Blood and lymphatic system disorders
Anaemia	17/39 (43.6%)		17/38 (44.7%)
Coagulopathy	2/39 (5.1%)		6/38 (15.8%)
Iron deficiency anaemia	3/39 (7.7%)		1/38 (2.6%)
Leukocytosis	2/39 (5.1%)		6/38 (15.8%)
Leukopenia	1/39 (2.6%)		4/38 (10.5%)
Thrombocytopenia	10/39 (25.6%)		11/38 (28.9%)
Thrombocytosis	1/39 (2.6%)		3/38 (7.9%)
Cardiac disorders
Arrhythmia	0/39 (0%)		2/38 (5.3%)
Bradycardia	1/39 (2.6%)		3/38 (7.9%)
Tachycardia	3/39 (7.7%)		2/38 (5.3%)
Endocrine disorders
Hyperparathyroidism	2/39 (5.1%)		1/38 (2.6%)
Hypothyroidism	3/39 (7.7%)		2/38 (5.3%)
Gastrointestinal disorders
Abdominal pain	8/39 (20.5%)		14/38 (36.8%)
Ascites	12/39 (30.8%)		12/38 (31.6%)
Constipation	15/39 (38.5%)		17/38 (44.7%)
Diarrhoea	6/39 (15.4%)		3/38 (7.9%)
Flatulence	20/39 (51.3%)		16/38 (42.1%)
Gingival hyperplasia	2/39 (5.1%)		0/38 (0%)
Nausea	6/39 (15.4%)		2/38 (5.3%)
Peritonitis	1/39 (2.6%)		2/38 (5.3%)
Vomiting	10/39 (25.6%)		15/38 (39.5%)
General disorders
Drug withdrawal syndrome	7/39 (17.9%)		7/38 (18.4%)
Obstruction	0/39 (0%)		2/38 (5.3%)
Oedema	1/39 (2.6%)		3/38 (7.9%)
Pain	2/39 (5.1%)		3/38 (7.9%)
Pyrexia	19/39 (48.7%)		25/38 (65.8%)
Systemic inflammatory response syndrome	0/39 (0%)		2/38 (5.3%)
Hepatobiliary disorders
Bile duct necrosis	0/39 (0%)		2/38 (5.3%)
Bile duct obstruction	2/39 (5.1%)		2/38 (5.3%)
Cholangitis	2/39 (5.1%)		0/38 (0%)
Cholestasis	1/39 (2.6%)		7/38 (18.4%)
Hepatic ischaemia	2/39 (5.1%)		0/38 (0%)
Hyperbilirubinaemia	2/39 (5.1%)		2/38 (5.3%)
Pneumobilia	3/39 (7.7%)		1/38 (2.6%)
Portal vein stenosis	1/39 (2.6%)		3/38 (7.9%)
Infections and infestations
Abdominal infection	2/39 (5.1%)		3/38 (7.9%)
Adenovirus infection	2/39 (5.1%)		0/38 (0%)
Bacterial infection	1/39 (2.6%)		3/38 (7.9%)
Bronchitis	3/39 (7.7%)		2/38 (5.3%)
Candidiasis	7/39 (17.9%)		11/38 (28.9%)
Cytomegalovirus infection	6/39 (15.4%)		6/38 (15.8%)
Enterococcal infection	1/39 (2.6%)		2/38 (5.3%)
Epstein-barr virus infection	7/39 (17.9%)		9/38 (23.7%)
Fungal infection	1/39 (2.6%)		2/38 (5.3%)
Gastroenteritis	4/39 (10.3%)		2/38 (5.3%)
Human herpesvirus 6 infection	2/39 (5.1%)		4/38 (10.5%)
Infection	4/39 (10.3%)		5/38 (13.2%)
Infectious disease carrier	6/39 (15.4%)		4/38 (10.5%)
Oral herpes	2/39 (5.1%)		1/38 (2.6%)
Pneumonia	0/39 (0%)		2/38 (5.3%)
Respiratory tract infection	1/39 (2.6%)		4/38 (10.5%)
Rhinitis	3/39 (7.7%)		3/38 (7.9%)
Sepsis	3/39 (7.7%)		4/38 (10.5%)
Staphylococcal infection	3/39 (7.7%)		2/38 (5.3%)
Wound infection	2/39 (5.1%)		1/38 (2.6%)
Injury, poisoning and procedural complications
Complications of transplanted liver	2/39 (5.1%)		0/38 (0%)
Hepatic haematoma	2/39 (5.1%)		2/38 (5.3%)
Post procedural bile leak	2/39 (5.1%)		2/38 (5.3%)
Procedural pain	2/39 (5.1%)		3/38 (7.9%)
Investigations
Antithrombin iii decreased	16/39 (41%)		16/38 (42.1%)
Blood magnesium decreased	2/39 (5.1%)		0/38 (0%)
Blood urea increased	1/39 (2.6%)		3/38 (7.9%)
C-reactive protein increased	3/39 (7.7%)		7/38 (18.4%)
Drug level decreased	0/39 (0%)		3/38 (7.9%)
Gamma-glutamyltransferase increased	0/39 (0%)		2/38 (5.3%)
Immunoglobulins decreased	2/39 (5.1%)		0/38 (0%)
Platelet count decreased	1/39 (2.6%)		2/38 (5.3%)
Red blood cell count decreased	2/39 (5.1%)		0/38 (0%)
Transaminases increased	5/39 (12.8%)		3/38 (7.9%)
Metabolism and nutrition disorders
Acidosis	5/39 (12.8%)		6/38 (15.8%)
Hyperglycaemia	8/39 (20.5%)		15/38 (39.5%)
Hyperkalaemia	8/39 (20.5%)		8/38 (21.1%)
Hyperlipidaemia	0/39 (0%)		2/38 (5.3%)
Hyperphosphataemia	3/39 (7.7%)		4/38 (10.5%)
Hypertriglyceridaemia	2/39 (5.1%)		1/38 (2.6%)
Hypoalbuminaemia	4/39 (10.3%)		4/38 (10.5%)
Hypocalcaemia	8/39 (20.5%)		15/38 (39.5%)
Hypoglycaemia	4/39 (10.3%)		2/38 (5.3%)
Hypokalaemia	8/39 (20.5%)		13/38 (34.2%)
Hypomagnesaemia	21/39 (53.8%)		15/38 (39.5%)
Hyponatraemia	6/39 (15.4%)		6/38 (15.8%)
Hypophosphataemia	5/39 (12.8%)		4/38 (10.5%)
Hypoproteinaemia	10/39 (25.6%)		5/38 (13.2%)
Hypovolaemia	0/39 (0%)		2/38 (5.3%)
Metabolic acidosis	1/39 (2.6%)		2/38 (5.3%)
Vitamin k deficiency	3/39 (7.7%)		2/38 (5.3%)
Musculoskeletal and connective tissue disorders
Back pain	0/39 (0%)		2/38 (5.3%)
Nervous system disorders
Headache	2/39 (5.1%)		1/38 (2.6%)
Psychiatric disorders
Insomnia	4/39 (10.3%)		4/38 (10.5%)
Restlessness	10/39 (25.6%)		14/38 (36.8%)
Renal and urinary disorders
Oliguria	2/39 (5.1%)		5/38 (13.2%)
Renal failure	3/39 (7.7%)		6/38 (15.8%)
Renal failure chronic	2/39 (5.1%)		2/38 (5.3%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	10/39 (25.6%)		12/38 (31.6%)
Chylothorax	1/39 (2.6%)		3/38 (7.9%)
Epistaxis	2/39 (5.1%)		3/38 (7.9%)
Obstructive airways disorder	11/39 (28.2%)		14/38 (36.8%)
Pleural effusion	18/39 (46.2%)		24/38 (63.2%)
Pneumothorax	3/39 (7.7%)		4/38 (10.5%)
Respiratory failure	2/39 (5.1%)		2/38 (5.3%)
Tachypnoea	0/39 (0%)		2/38 (5.3%)
Skin and subcutaneous tissue disorders
Hirsutism	1/39 (2.6%)		3/38 (7.9%)
Petechiae	0/39 (0%)		2/38 (5.3%)
Rash	3/39 (7.7%)		3/38 (7.9%)
Vascular disorders
Hypertension	29/39 (74.4%)		27/38 (71.1%)
Hypotension	7/39 (17.9%)		8/38 (21.1%)
Intra-abdominal haemorrhage	1/39 (2.6%)		3/38 (7.9%)
Vena cava thrombosis	2/39 (5.1%)		0/38 (0%)

Limitations/Caveats

[Not Specified]

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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.