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Trial record 20 of 881 for:    Liver Transplant

Extension Study to Evaluate the Long-term Efficacy and Safety of Everolimus in Liver Transplant Recipients

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ClinicalTrials.gov Identifier: NCT01150097
Recruitment Status : Completed
First Posted : June 24, 2010
Results First Posted : May 30, 2014
Last Update Posted : November 7, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Liver Transplant Recipient
Interventions Drug: Tacrolimus (reduced tacrolimus)
Drug: Everolimus (reduced tacrolimus)
Drug: Tacrolimus (tacrolimus elimination)
Drug: Everolimus (tacrolimus elimination)
Drug: Tacrolimus (tacrolimus control)
Drug: Corticosteroids
Enrollment 284
Recruitment Details Two hundred eight four participants were eligible and enrolled into the extension. However, 2 participants withdrew from the extension prior to receiving treatment. Therefore, a total of 282 participants were accounted for in the extension.
Pre-assignment Details Participants in the tacrolimus control group were studied for 12 months (from months 24 to 36 post transplant). Participants in the tacrolimus elimination and everolimus + reduced tacrolimus groups were studied for a minimum of 12 months up to 24 months (from months 24 to 48 months post transplant) depending on the participant's study start.
Arm/Group Title Everolimus + Reduced Tacrolimus Tacrolimus Elimination Tacrolimus Control
Hide Arm/Group Description Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus. Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus. Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.
Period Title: Months 24 to 36 Post-transplantation
Started 106 51 125
Completed 96 49 117
Not Completed 10 2 8
Reason Not Completed
Death             2             0             0
Administrative problems             5             2             2
Lost to Follow-up             0             0             3
Withdrawal by Subject             3             0             3
Period Title: Months 24 to 48 Post-transplantation
Started 106 51 0
Completed 95 47 0
Not Completed 11 4 0
Reason Not Completed
Administrative problems             5             4             0
Withdrawal by Subject             4             0             0
Death             2             0             0
Arm/Group Title Everolimus + Reduced Tacrolimus Tacrolimus Elimination Tacrolimus Control Total
Hide Arm/Group Description Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus. Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus. Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus. Total of all reporting groups
Overall Number of Baseline Participants 106 51 125 282
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 106 participants 51 participants 125 participants 282 participants
53.5  (9.57) 54.9  (10.07) 55.2  (8.10) 54.5  (9.25)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 51 participants 125 participants 282 participants
Female
29
  27.4%
18
  35.3%
38
  30.4%
85
  30.1%
Male
77
  72.6%
33
  64.7%
87
  69.6%
197
  69.9%
1.Primary Outcome
Title Incidence Rate of Composite Efficacy Failure Defined as Treated Biopsy Proven Acute Rejection (tBPAR ), Graft Loss or Death
Hide Description The number of participants who experienced composite efficacy failure was analyzed. Composite efficacy failure was defined as treated biopsy proven acute rejection (tBPAR), graft loss, or death. A BPAR was defined as an acute rejection confirmed by biopsy with a Rejection Activity Index (RAI) score ≥ 3. tBPAR was defined as a BPAR which was treated with anti-rejection therapy. The RAI is used to score liver biopsies with acute rejection and is composed of 3 categories (portal inflammation, bile duct inflammation damage, and venous endothelial inflammation) each scored on a scale of 0 (absent) to 3 (severe) by a trained pathologist. The total RAI score = the sum of the scores of the 3 categories and ranges from 0 to 9, with a higher score indicating greater rejection. The graft was presumed to be lost on the day the patient was newly listed for a liver graft, received a graft re-transplant, or died.
Time Frame from months 24 to 36
Hide Outcome Measure Data
Hide Analysis Population Description
All extension participants
Arm/Group Title Everolimus + Reduced Tacrolimus Tacrolimus Elimination Tacrolimus Control
Hide Arm/Group Description:
Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.
Overall Number of Participants Analyzed 106 51 125
Measure Type: Number
Unit of Measure: Participants
2 1 3
2.Primary Outcome
Title Incidence Rate of Composite Efficacy Failure Defined as Treated Biopsy Proven Acute Rejection (tBPAR ), Graft Loss or Death
Hide Description The number of participants who experienced composite efficacy failure was analyzed. Composite efficacy failure was defined as treated biopsy proven acute rejection (tBPAR), graft loss, or death. A BPAR was defined as an acute rejection confirmed by biopsy with a Rejection Activity Index (RAI) score ≥ 3. tBPAR was defined as a BPAR which was treated with anti-rejection therapy. The RAI is used to score liver biopsies with acute rejection and is composed of 3 categories (portal inflammation, bile duct inflammation damage, and venous endothelial inflammation) each scored on a scale of 0 (absent) to 3 (severe) by a trained pathologist. The total RAI score = the sum of the scores of the 3 categories and ranges from 0 to 9, with a higher score indicating greater rejection. The graft was presumed to be lost on the day the patient was newly listed for a liver graft, received a graft re-transplant, or died.
Time Frame from months 36 to 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the everolimus + reduced tacrolimus group and the tacrolimus elimination group
Arm/Group Title Everolimus + Reduced Tacrolimus Tacrolimus Elimination
Hide Arm/Group Description:
Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
Overall Number of Participants Analyzed 106 51
Measure Type: Number
Unit of Measure: Participants
1 0
3.Primary Outcome
Title Incidence Rate of Composite Efficacy Failure Defined as Graft Loss or Death
Hide Description The number of participants who experienced graft loss or death was analyzed. The graft was presumed to be lost on the day the patient was newly listed for a liver graft, received a graft re-transplant, or died.
Time Frame from months 24 to 36
Hide Outcome Measure Data
Hide Analysis Population Description
All extension participants
Arm/Group Title Everolimus + Reduced Tacrolimus Tacrolimus Elimination Tacrolimus Control
Hide Arm/Group Description:
Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.
Overall Number of Participants Analyzed 106 51 125
Measure Type: Number
Unit of Measure: Participants
2 0 1
4.Primary Outcome
Title Incidence Rate of Composite Efficacy Failure Defined as Graft Loss or Death
Hide Description The number of participants who experienced graft loss or death was analyzed. The graft was presumed to be lost on the day the patient was newly listed for a liver graft, received a graft re-transplant, or died.
Time Frame from months 36 - 48
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the everolimus + reduced tacrolimus group and the tacrolimus elimination group
Arm/Group Title Everolimus + Reduced Tacrolimus Tacrolimus Elimination
Hide Arm/Group Description:
Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
Overall Number of Participants Analyzed 106 51
Measure Type: Number
Unit of Measure: Participants
0 0
5.Primary Outcome
Title Change in Renal Function
Hide Description Change in renal function was assessed by the estimated Glomerular Filtration Rate (eGFR) using the abbreviated (4 variables) Modification of Diet in Renal Disease (MDRD-4) formula which was developed by the MDRD Study Group and has been validated in patients with chronic kidney disease. The MDRD-4 formula used for the eGFR calculation is: eGFR (mL/min/1.73m^2) = 186.3*(C^-1.154)*(A^-0.203)*G*R, where C is the serum concentration of creatinine (mg/dL), A is age (years), G=0.742 when gender is female, otherwise G=1, R=1.21 when race is black, otherwise R=1.
Time Frame from months 24 to 36
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included extension participants who had both post-extension baseline and month 36 values only.
Arm/Group Title Everolimus + Reduced Tacrolimus Tacrolimus Elimination Tacrolimus Control
Hide Arm/Group Description:
Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.
Overall Number of Participants Analyzed 100 50 115
Mean (Standard Deviation)
Unit of Measure: mL/min/1.73m^2
-0.9  (16.13) 2.5  (12.40) -3.3  (11.84)
6.Secondary Outcome
Title Incidence Rate of tBPAR
Hide Description The number of participants who had a tBPAR was analyzed. tBPAR was defined as a BPAR which was treated with anti-rejection therapy. The RAI is used to score liver biopsies with acute rejection and is composed of 3 categories (portal inflammation, bile duct inflammation damage, and venous endothelial inflammation) each scored on a scale of 0 (absent) to 3 (severe) by a trained pathologist. The total RAI score = the sum of the scores of the 3 categories and ranges from 0 to 9, with a higher score indicating greater rejection.
Time Frame from months 24 - 36
Hide Outcome Measure Data
Hide Analysis Population Description
All extension participants
Arm/Group Title Everolimus + Reduced Tacrolimus Tacrolimus Elimination Tacrolimus Control
Hide Arm/Group Description:
Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.
Overall Number of Participants Analyzed 106 51 125
Measure Type: Number
Unit of Measure: Participants
0 1 2
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Reduced TAC, Month 36 TAC Elimination, Month 36 TAC Control, Month 36 Reduced RAD + TAC, Month 48 TAC Elimination, Month 48
Hide Arm/Group Description Reduced TAC, Month 36 TAC Elimination, Month 36 TAC Control, Month 36 Reduced RAD + TAC, Month 48 TAC Elimination, Month 48
All-Cause Mortality
Reduced TAC, Month 36 TAC Elimination, Month 36 TAC Control, Month 36 Reduced RAD + TAC, Month 48 TAC Elimination, Month 48
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Reduced TAC, Month 36 TAC Elimination, Month 36 TAC Control, Month 36 Reduced RAD + TAC, Month 48 TAC Elimination, Month 48
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   32/106 (30.19%)   16/51 (31.37%)   28/125 (22.40%)   34/106 (32.08%)   24/51 (47.06%) 
Blood and lymphatic system disorders           
Anaemia  1  0/106 (0.00%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Haemolytic uraemic syndrome  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Lymphadenopathy  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Splenomegaly  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Cardiac disorders           
Acute myocardial infarction  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Cardiac failure  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Coronary artery stenosis  1  0/106 (0.00%)  0/51 (0.00%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Myocardial infarction  1  1/106 (0.94%)  0/51 (0.00%)  1/125 (0.80%)  1/106 (0.94%)  0/51 (0.00%) 
Tachycardia  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Gastrointestinal disorders           
Abdominal adhesions  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Abdominal hernia  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Abdominal pain  1  1/106 (0.94%)  0/51 (0.00%)  1/125 (0.80%)  1/106 (0.94%)  1/51 (1.96%) 
Abdominal strangulated hernia  1  0/106 (0.00%)  1/51 (1.96%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Constipation  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Crohn's disease  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Diarrhoea  1  3/106 (2.83%)  0/51 (0.00%)  2/125 (1.60%)  4/106 (3.77%)  0/51 (0.00%) 
Gastrointestinal obstruction  1  0/106 (0.00%)  0/51 (0.00%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Hernial eventration  1  1/106 (0.94%)  0/51 (0.00%)  2/125 (1.60%)  1/106 (0.94%)  0/51 (0.00%) 
Intestinal obstruction  1  0/106 (0.00%)  0/51 (0.00%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Mouth ulceration  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Nausea  1  1/106 (0.94%)  0/51 (0.00%)  1/125 (0.80%)  1/106 (0.94%)  1/51 (1.96%) 
Oesophageal ulcer  1  0/106 (0.00%)  0/51 (0.00%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Rectal haemorrhage  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Small intestinal obstruction  1  0/106 (0.00%)  1/51 (1.96%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Stomatitis  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Umbilical hernia, obstructive  1  0/106 (0.00%)  1/51 (1.96%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Vomiting  1  2/106 (1.89%)  0/51 (0.00%)  2/125 (1.60%)  2/106 (1.89%)  1/51 (1.96%) 
General disorders           
Device occlusion  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
General physical health deterioration  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Generalised oedema  1  0/106 (0.00%)  1/51 (1.96%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Impaired healing  1  2/106 (1.89%)  1/51 (1.96%)  0/125 (0.00%)  2/106 (1.89%)  2/51 (3.92%) 
Oedema peripheral  1  0/106 (0.00%)  1/51 (1.96%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Pyrexia  1  3/106 (2.83%)  2/51 (3.92%)  2/125 (1.60%)  3/106 (2.83%)  4/51 (7.84%) 
Sudden death  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Hepatobiliary disorders           
Acute hepatic failure  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Autoimmune hepatitis  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Bile duct stenosis  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Biliary ischaemia  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Cholangitis  1  1/106 (0.94%)  1/51 (1.96%)  0/125 (0.00%)  1/106 (0.94%)  1/51 (1.96%) 
Cholestasis  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Hepatic artery thrombosis  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Hepatic necrosis  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Hepatic steatosis  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Portal vein thrombosis  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Infections and infestations           
Abdominal sepsis  1  0/106 (0.00%)  0/51 (0.00%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Arthritis bacterial  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Bacteraemia  1  0/106 (0.00%)  1/51 (1.96%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Bronchitis  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Cellulitis  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  2/106 (1.89%)  1/51 (1.96%) 
Epstein-Barr viraemia  1  0/106 (0.00%)  0/51 (0.00%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Erysipelas  1  0/106 (0.00%)  1/51 (1.96%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Gastroenteritis  1  2/106 (1.89%)  0/51 (0.00%)  1/125 (0.80%)  2/106 (1.89%)  0/51 (0.00%) 
Haematoma infection  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Hepatitis C  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Liver abscess  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Localised infection  1  0/106 (0.00%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Oral herpes  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Orchitis  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Paronychia  1  0/106 (0.00%)  1/51 (1.96%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Pneumonia  1  2/106 (1.89%)  2/51 (3.92%)  3/125 (2.40%)  3/106 (2.83%)  3/51 (5.88%) 
Respiratory tract infection  1  0/106 (0.00%)  1/51 (1.96%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Sepsis  1  2/106 (1.89%)  1/51 (1.96%)  0/125 (0.00%)  2/106 (1.89%)  1/51 (1.96%) 
Septic shock  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Sinusitis  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Streptococcal sepsis  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Urinary tract infection  1  1/106 (0.94%)  1/51 (1.96%)  2/125 (1.60%)  1/106 (0.94%)  1/51 (1.96%) 
Viral infection  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Wound abscess  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Injury, poisoning and procedural complications           
Anastomotic stenosis  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Ankle fracture  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  2/106 (1.89%)  0/51 (0.00%) 
Clavicle fracture  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Graft loss  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Incisional hernia  1  1/106 (0.94%)  2/51 (3.92%)  1/125 (0.80%)  2/106 (1.89%)  4/51 (7.84%) 
Incisional hernia, obstructive  1  0/106 (0.00%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  1/51 (1.96%) 
Joint dislocation  1  0/106 (0.00%)  1/51 (1.96%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Lower limb fracture  1  0/106 (0.00%)  1/51 (1.96%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Overdose  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Pelvic fracture  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Post procedural bile leak  1  0/106 (0.00%)  0/51 (0.00%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Postoperative hernia  1  0/106 (0.00%)  1/51 (1.96%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Radius fracture  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Tendon rupture  1  0/106 (0.00%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Wound dehiscence  1  0/106 (0.00%)  1/51 (1.96%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Investigations           
Blood creatinine increased  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Blood glucose increased  1  0/106 (0.00%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Haemoglobin decreased  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Weight decreased  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  1/106 (0.94%)  0/51 (0.00%) 
Metabolism and nutrition disorders           
Gout  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  1/51 (1.96%) 
Hyperglycaemia  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Hyperkalaemia  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Hypokalaemia  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Hyponatraemia  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Musculoskeletal and connective tissue disorders           
Osteonecrosis  1  0/106 (0.00%)  1/51 (1.96%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Basal cell carcinoma  1  0/106 (0.00%)  0/51 (0.00%)  2/125 (1.60%)  0/106 (0.00%)  0/51 (0.00%) 
Diffuse large B-cell lymphoma  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Hepatocellular carcinoma  1  1/106 (0.94%)  0/51 (0.00%)  1/125 (0.80%)  1/106 (0.94%)  0/51 (0.00%) 
Lung neoplasm malignant  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Oesophageal squamous cell carcinoma  1  0/106 (0.00%)  0/51 (0.00%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Prostate cancer  1  0/106 (0.00%)  0/51 (0.00%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Squamous cell carcinoma  1  0/106 (0.00%)  0/51 (0.00%)  2/125 (1.60%)  0/106 (0.00%)  1/51 (1.96%) 
Squamous cell carcinoma of lung  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Squamous cell carcinoma of skin  1  0/106 (0.00%)  0/51 (0.00%)  2/125 (1.60%)  0/106 (0.00%)  0/51 (0.00%) 
Nervous system disorders           
Cerebral ischaemia  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Dysarthria  1  0/106 (0.00%)  0/51 (0.00%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Haemorrhage intracranial  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Headache  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Psychiatric disorders           
Depression  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Suicide attempt  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Renal and urinary disorders           
Acute prerenal failure  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Renal failure  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Renal failure acute  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Renal failure chronic  1  0/106 (0.00%)  1/51 (1.96%)  0/125 (0.00%)  0/106 (0.00%)  1/51 (1.96%) 
Renal impairment  1  0/106 (0.00%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Renal injury  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Reproductive system and breast disorders           
Gynaecomastia  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Ovarian cyst  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Pleural effusion  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Pulmonary granuloma  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Skin and subcutaneous tissue disorders           
Night sweats  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Pruritus  1  0/106 (0.00%)  0/51 (0.00%)  1/125 (0.80%)  0/106 (0.00%)  0/51 (0.00%) 
Vascular disorders           
Haematoma  1  1/106 (0.94%)  0/51 (0.00%)  0/125 (0.00%)  1/106 (0.94%)  0/51 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Reduced TAC, Month 36 TAC Elimination, Month 36 TAC Control, Month 36 Reduced RAD + TAC, Month 48 TAC Elimination, Month 48
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   38/106 (35.85%)   29/51 (56.86%)   43/125 (34.40%)   43/106 (40.57%)   36/51 (70.59%) 
Blood and lymphatic system disorders           
Anaemia  1  4/106 (3.77%)  3/51 (5.88%)  3/125 (2.40%)  4/106 (3.77%)  3/51 (5.88%) 
Thrombocytopenia  1  0/106 (0.00%)  1/51 (1.96%)  1/125 (0.80%)  0/106 (0.00%)  4/51 (7.84%) 
Gastrointestinal disorders           
Abdominal pain  1  2/106 (1.89%)  2/51 (3.92%)  8/125 (6.40%)  3/106 (2.83%)  4/51 (7.84%) 
Diarrhoea  1  10/106 (9.43%)  3/51 (5.88%)  4/125 (3.20%)  13/106 (12.26%)  4/51 (7.84%) 
Nausea  1  3/106 (2.83%)  1/51 (1.96%)  9/125 (7.20%)  5/106 (4.72%)  2/51 (3.92%) 
General disorders           
Fatigue  1  1/106 (0.94%)  2/51 (3.92%)  10/125 (8.00%)  2/106 (1.89%)  6/51 (11.76%) 
Oedema peripheral  1  4/106 (3.77%)  4/51 (7.84%)  2/125 (1.60%)  6/106 (5.66%)  5/51 (9.80%) 
Infections and infestations           
Hepatitis C  1  1/106 (0.94%)  2/51 (3.92%)  3/125 (2.40%)  1/106 (0.94%)  3/51 (5.88%) 
Influenza  1  2/106 (1.89%)  3/51 (5.88%)  0/125 (0.00%)  2/106 (1.89%)  3/51 (5.88%) 
Nasopharyngitis  1  5/106 (4.72%)  5/51 (9.80%)  4/125 (3.20%)  6/106 (5.66%)  5/51 (9.80%) 
Urinary tract infection  1  4/106 (3.77%)  2/51 (3.92%)  4/125 (3.20%)  4/106 (3.77%)  4/51 (7.84%) 
Injury, poisoning and procedural complications           
Incisional hernia  1  2/106 (1.89%)  6/51 (11.76%)  2/125 (1.60%)  2/106 (1.89%)  7/51 (13.73%) 
Metabolism and nutrition disorders           
Hypercholesterolaemia  1  6/106 (5.66%)  4/51 (7.84%)  3/125 (2.40%)  7/106 (6.60%)  5/51 (9.80%) 
Musculoskeletal and connective tissue disorders           
Osteoporosis  1  0/106 (0.00%)  3/51 (5.88%)  1/125 (0.80%)  0/106 (0.00%)  3/51 (5.88%) 
Pain in extremity  1  2/106 (1.89%)  3/51 (5.88%)  0/125 (0.00%)  2/106 (1.89%)  5/51 (9.80%) 
Renal and urinary disorders           
Renal failure  1  1/106 (0.94%)  1/51 (1.96%)  10/125 (8.00%)  2/106 (1.89%)  1/51 (1.96%) 
Vascular disorders           
Hypertension  1  8/106 (7.55%)  2/51 (3.92%)  5/125 (4.00%)  9/106 (8.49%)  2/51 (3.92%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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 or disclosure of trial results in their entirety.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01150097     History of Changes
Other Study ID Numbers: CRAD001H2304E1
2009-017311-15
First Submitted: April 23, 2010
First Posted: June 24, 2010
Results First Submitted: May 1, 2014
Results First Posted: May 30, 2014
Last Update Posted: November 7, 2018