Trial Outcomes & Findings for Extension Study to Evaluate the Long-term Efficacy and Safety of Everolimus in Liver Transplant Recipients (NCT NCT01150097)
NCT ID: NCT01150097
Last Updated: 2018-11-07
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
284 participants
Primary outcome timeframe
from months 24 to 36
Results posted on
2018-11-07
Participant Flow
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.
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.
Participant milestones
| Measure |
Everolimus + Reduced Tacrolimus
Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
|
Tacrolimus Elimination
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
|
Tacrolimus Control
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.
|
|---|---|---|---|
|
Months 24 to 36 Post-transplantation
STARTED
|
106
|
51
|
125
|
|
Months 24 to 36 Post-transplantation
COMPLETED
|
96
|
49
|
117
|
|
Months 24 to 36 Post-transplantation
NOT COMPLETED
|
10
|
2
|
8
|
|
Months 24 to 48 Post-transplantation
STARTED
|
106
|
51
|
0
|
|
Months 24 to 48 Post-transplantation
COMPLETED
|
95
|
47
|
0
|
|
Months 24 to 48 Post-transplantation
NOT COMPLETED
|
11
|
4
|
0
|
Reasons for withdrawal
| Measure |
Everolimus + Reduced Tacrolimus
Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
|
Tacrolimus Elimination
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
|
Tacrolimus Control
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.
|
|---|---|---|---|
|
Months 24 to 36 Post-transplantation
Death
|
2
|
0
|
0
|
|
Months 24 to 36 Post-transplantation
Administrative problems
|
5
|
2
|
2
|
|
Months 24 to 36 Post-transplantation
Lost to Follow-up
|
0
|
0
|
3
|
|
Months 24 to 36 Post-transplantation
Withdrawal by Subject
|
3
|
0
|
3
|
|
Months 24 to 48 Post-transplantation
Administrative problems
|
5
|
4
|
0
|
|
Months 24 to 48 Post-transplantation
Withdrawal by Subject
|
4
|
0
|
0
|
|
Months 24 to 48 Post-transplantation
Death
|
2
|
0
|
0
|
Baseline Characteristics
Extension Study to Evaluate the Long-term Efficacy and Safety of Everolimus in Liver Transplant Recipients
Baseline characteristics by cohort
| Measure |
Everolimus + Reduced Tacrolimus
n=106 Participants
Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
|
Tacrolimus Elimination
n=51 Participants
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
|
Tacrolimus Control
n=125 Participants
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.
|
Total
n=282 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
53.5 Years
STANDARD_DEVIATION 9.57 • n=5 Participants
|
54.9 Years
STANDARD_DEVIATION 10.07 • n=7 Participants
|
55.2 Years
STANDARD_DEVIATION 8.10 • n=5 Participants
|
54.5 Years
STANDARD_DEVIATION 9.25 • n=4 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
85 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
77 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
87 Participants
n=5 Participants
|
197 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: from months 24 to 36Population: All extension participants
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.
Outcome measures
| Measure |
Tacrolimus Elimination
n=51 Participants
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
|
Tacrolimus Control
n=125 Participants
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.
|
Everolimus + Reduced Tacrolimus
n=106 Participants
Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
|
|---|---|---|---|
|
Incidence Rate of Composite Efficacy Failure Defined as Treated Biopsy Proven Acute Rejection (tBPAR ), Graft Loss or Death
|
1 Participants
|
3 Participants
|
2 Participants
|
PRIMARY outcome
Timeframe: from months 36 to 48Population: Participants from the everolimus + reduced tacrolimus group and the tacrolimus elimination group
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.
Outcome measures
| Measure |
Tacrolimus Elimination
n=51 Participants
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
|
Tacrolimus Control
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.
|
Everolimus + Reduced Tacrolimus
n=106 Participants
Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
|
|---|---|---|---|
|
Incidence Rate of Composite Efficacy Failure Defined as Treated Biopsy Proven Acute Rejection (tBPAR ), Graft Loss or Death
|
0 Participants
|
—
|
1 Participants
|
PRIMARY outcome
Timeframe: from months 24 to 36Population: All extension participants
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.
Outcome measures
| Measure |
Tacrolimus Elimination
n=51 Participants
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
|
Tacrolimus Control
n=125 Participants
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.
|
Everolimus + Reduced Tacrolimus
n=106 Participants
Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
|
|---|---|---|---|
|
Incidence Rate of Composite Efficacy Failure Defined as Graft Loss or Death
|
0 Participants
|
1 Participants
|
2 Participants
|
PRIMARY outcome
Timeframe: from months 36 - 48Population: Participants from the everolimus + reduced tacrolimus group and the tacrolimus elimination group
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.
Outcome measures
| Measure |
Tacrolimus Elimination
n=51 Participants
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
|
Tacrolimus Control
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.
|
Everolimus + Reduced Tacrolimus
n=106 Participants
Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
|
|---|---|---|---|
|
Incidence Rate of Composite Efficacy Failure Defined as Graft Loss or Death
|
0 Participants
|
—
|
0 Participants
|
PRIMARY outcome
Timeframe: from months 24 to 36Population: The analysis population included extension participants who had both post-extension baseline and month 36 values only.
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.
Outcome measures
| Measure |
Tacrolimus Elimination
n=50 Participants
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
|
Tacrolimus Control
n=115 Participants
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.
|
Everolimus + Reduced Tacrolimus
n=100 Participants
Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
|
|---|---|---|---|
|
Change in Renal Function
|
2.5 mL/min/1.73m^2
Standard Deviation 12.40
|
-3.3 mL/min/1.73m^2
Standard Deviation 11.84
|
-0.9 mL/min/1.73m^2
Standard Deviation 16.13
|
SECONDARY outcome
Timeframe: from months 24 - 36Population: All extension participants
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.
Outcome measures
| Measure |
Tacrolimus Elimination
n=51 Participants
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
|
Tacrolimus Control
n=125 Participants
Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.
|
Everolimus + Reduced Tacrolimus
n=106 Participants
Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
|
|---|---|---|---|
|
Incidence Rate of tBPAR
|
1 Participants
|
2 Participants
|
0 Participants
|
Adverse Events
Reduced TAC, Month 36
Serious events: 32 serious events
Other events: 38 other events
Deaths: 0 deaths
TAC Elimination, Month 36
Serious events: 16 serious events
Other events: 29 other events
Deaths: 0 deaths
TAC Control, Month 36
Serious events: 28 serious events
Other events: 43 other events
Deaths: 0 deaths
Reduced RAD + TAC, Month 48
Serious events: 34 serious events
Other events: 43 other events
Deaths: 0 deaths
TAC Elimination, Month 48
Serious events: 24 serious events
Other events: 36 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Reduced TAC, Month 36
n=106 participants at risk
Reduced TAC, Month 36
|
TAC Elimination, Month 36
n=51 participants at risk
TAC Elimination, Month 36
|
TAC Control, Month 36
n=125 participants at risk
TAC Control, Month 36
|
Reduced RAD + TAC, Month 48
n=106 participants at risk
Reduced RAD + TAC, Month 48
|
TAC Elimination, Month 48
n=51 participants at risk
TAC Elimination, Month 48
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Blood and lymphatic system disorders
Haemolytic uraemic syndrome
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Blood and lymphatic system disorders
Splenomegaly
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Cardiac disorders
Coronary artery stenosis
|
0.00%
0/106
|
0.00%
0/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Cardiac disorders
Myocardial infarction
|
0.94%
1/106
|
0.00%
0/51
|
0.80%
1/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Cardiac disorders
Tachycardia
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Gastrointestinal disorders
Abdominal adhesions
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Gastrointestinal disorders
Abdominal hernia
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Gastrointestinal disorders
Abdominal pain
|
0.94%
1/106
|
0.00%
0/51
|
0.80%
1/125
|
0.94%
1/106
|
2.0%
1/51
|
|
Gastrointestinal disorders
Abdominal strangulated hernia
|
0.00%
0/106
|
2.0%
1/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Gastrointestinal disorders
Constipation
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Gastrointestinal disorders
Crohn's disease
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Gastrointestinal disorders
Diarrhoea
|
2.8%
3/106
|
0.00%
0/51
|
1.6%
2/125
|
3.8%
4/106
|
0.00%
0/51
|
|
Gastrointestinal disorders
Gastrointestinal obstruction
|
0.00%
0/106
|
0.00%
0/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Gastrointestinal disorders
Hernial eventration
|
0.94%
1/106
|
0.00%
0/51
|
1.6%
2/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/106
|
0.00%
0/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Gastrointestinal disorders
Mouth ulceration
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Gastrointestinal disorders
Nausea
|
0.94%
1/106
|
0.00%
0/51
|
0.80%
1/125
|
0.94%
1/106
|
2.0%
1/51
|
|
Gastrointestinal disorders
Oesophageal ulcer
|
0.00%
0/106
|
0.00%
0/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/106
|
2.0%
1/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Gastrointestinal disorders
Stomatitis
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Gastrointestinal disorders
Umbilical hernia, obstructive
|
0.00%
0/106
|
2.0%
1/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Gastrointestinal disorders
Vomiting
|
1.9%
2/106
|
0.00%
0/51
|
1.6%
2/125
|
1.9%
2/106
|
2.0%
1/51
|
|
General disorders
Device occlusion
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
General disorders
General physical health deterioration
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
General disorders
Generalised oedema
|
0.00%
0/106
|
2.0%
1/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
General disorders
Impaired healing
|
1.9%
2/106
|
2.0%
1/51
|
0.00%
0/125
|
1.9%
2/106
|
3.9%
2/51
|
|
General disorders
Oedema peripheral
|
0.00%
0/106
|
2.0%
1/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
General disorders
Pyrexia
|
2.8%
3/106
|
3.9%
2/51
|
1.6%
2/125
|
2.8%
3/106
|
7.8%
4/51
|
|
General disorders
Sudden death
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Hepatobiliary disorders
Acute hepatic failure
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Hepatobiliary disorders
Autoimmune hepatitis
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Hepatobiliary disorders
Bile duct stenosis
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Hepatobiliary disorders
Biliary ischaemia
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Hepatobiliary disorders
Cholangitis
|
0.94%
1/106
|
2.0%
1/51
|
0.00%
0/125
|
0.94%
1/106
|
2.0%
1/51
|
|
Hepatobiliary disorders
Cholestasis
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Hepatobiliary disorders
Hepatic artery thrombosis
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Hepatobiliary disorders
Hepatic necrosis
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Hepatobiliary disorders
Hepatic steatosis
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Infections and infestations
Abdominal sepsis
|
0.00%
0/106
|
0.00%
0/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Infections and infestations
Arthritis bacterial
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/106
|
2.0%
1/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Infections and infestations
Bronchitis
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Infections and infestations
Cellulitis
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
1.9%
2/106
|
2.0%
1/51
|
|
Infections and infestations
Epstein-Barr viraemia
|
0.00%
0/106
|
0.00%
0/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Infections and infestations
Erysipelas
|
0.00%
0/106
|
2.0%
1/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Infections and infestations
Gastroenteritis
|
1.9%
2/106
|
0.00%
0/51
|
0.80%
1/125
|
1.9%
2/106
|
0.00%
0/51
|
|
Infections and infestations
Haematoma infection
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Infections and infestations
Hepatitis C
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Infections and infestations
Liver abscess
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Infections and infestations
Localised infection
|
0.00%
0/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Infections and infestations
Oral herpes
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Infections and infestations
Orchitis
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Infections and infestations
Paronychia
|
0.00%
0/106
|
2.0%
1/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Infections and infestations
Pneumonia
|
1.9%
2/106
|
3.9%
2/51
|
2.4%
3/125
|
2.8%
3/106
|
5.9%
3/51
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/106
|
2.0%
1/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Infections and infestations
Sepsis
|
1.9%
2/106
|
2.0%
1/51
|
0.00%
0/125
|
1.9%
2/106
|
2.0%
1/51
|
|
Infections and infestations
Septic shock
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Infections and infestations
Sinusitis
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Infections and infestations
Streptococcal sepsis
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Infections and infestations
Urinary tract infection
|
0.94%
1/106
|
2.0%
1/51
|
1.6%
2/125
|
0.94%
1/106
|
2.0%
1/51
|
|
Infections and infestations
Viral infection
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Infections and infestations
Wound abscess
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Injury, poisoning and procedural complications
Anastomotic stenosis
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
1.9%
2/106
|
0.00%
0/51
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Injury, poisoning and procedural complications
Graft loss
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
0.94%
1/106
|
3.9%
2/51
|
0.80%
1/125
|
1.9%
2/106
|
7.8%
4/51
|
|
Injury, poisoning and procedural complications
Incisional hernia, obstructive
|
0.00%
0/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
2.0%
1/51
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.00%
0/106
|
2.0%
1/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.00%
0/106
|
2.0%
1/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Injury, poisoning and procedural complications
Overdose
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Injury, poisoning and procedural complications
Post procedural bile leak
|
0.00%
0/106
|
0.00%
0/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Injury, poisoning and procedural complications
Postoperative hernia
|
0.00%
0/106
|
2.0%
1/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.00%
0/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
0.00%
0/106
|
2.0%
1/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Investigations
Blood creatinine increased
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Investigations
Blood glucose increased
|
0.00%
0/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Investigations
Haemoglobin decreased
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Investigations
Weight decreased
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Metabolism and nutrition disorders
Gout
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
2.0%
1/51
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
0.00%
0/106
|
2.0%
1/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/106
|
0.00%
0/51
|
1.6%
2/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Diffuse large B-cell lymphoma
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma
|
0.94%
1/106
|
0.00%
0/51
|
0.80%
1/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal squamous cell carcinoma
|
0.00%
0/106
|
0.00%
0/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/106
|
0.00%
0/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.00%
0/106
|
0.00%
0/51
|
1.6%
2/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of lung
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
0.00%
0/106
|
0.00%
0/51
|
1.6%
2/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Nervous system disorders
Cerebral ischaemia
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Nervous system disorders
Dysarthria
|
0.00%
0/106
|
0.00%
0/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Nervous system disorders
Headache
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Psychiatric disorders
Depression
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Psychiatric disorders
Suicide attempt
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Renal and urinary disorders
Acute prerenal failure
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Renal and urinary disorders
Renal failure
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Renal and urinary disorders
Renal failure acute
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Renal and urinary disorders
Renal failure chronic
|
0.00%
0/106
|
2.0%
1/51
|
0.00%
0/125
|
0.00%
0/106
|
2.0%
1/51
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Renal and urinary disorders
Renal injury
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Reproductive system and breast disorders
Gynaecomastia
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Reproductive system and breast disorders
Ovarian cyst
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary granuloma
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/106
|
0.00%
0/51
|
0.80%
1/125
|
0.00%
0/106
|
0.00%
0/51
|
|
Vascular disorders
Haematoma
|
0.94%
1/106
|
0.00%
0/51
|
0.00%
0/125
|
0.94%
1/106
|
0.00%
0/51
|
Other adverse events
| Measure |
Reduced TAC, Month 36
n=106 participants at risk
Reduced TAC, Month 36
|
TAC Elimination, Month 36
n=51 participants at risk
TAC Elimination, Month 36
|
TAC Control, Month 36
n=125 participants at risk
TAC Control, Month 36
|
Reduced RAD + TAC, Month 48
n=106 participants at risk
Reduced RAD + TAC, Month 48
|
TAC Elimination, Month 48
n=51 participants at risk
TAC Elimination, Month 48
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
3.8%
4/106
|
5.9%
3/51
|
2.4%
3/125
|
3.8%
4/106
|
5.9%
3/51
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/106
|
2.0%
1/51
|
0.80%
1/125
|
0.00%
0/106
|
7.8%
4/51
|
|
Gastrointestinal disorders
Abdominal pain
|
1.9%
2/106
|
3.9%
2/51
|
6.4%
8/125
|
2.8%
3/106
|
7.8%
4/51
|
|
Gastrointestinal disorders
Diarrhoea
|
9.4%
10/106
|
5.9%
3/51
|
3.2%
4/125
|
12.3%
13/106
|
7.8%
4/51
|
|
Gastrointestinal disorders
Nausea
|
2.8%
3/106
|
2.0%
1/51
|
7.2%
9/125
|
4.7%
5/106
|
3.9%
2/51
|
|
General disorders
Fatigue
|
0.94%
1/106
|
3.9%
2/51
|
8.0%
10/125
|
1.9%
2/106
|
11.8%
6/51
|
|
General disorders
Oedema peripheral
|
3.8%
4/106
|
7.8%
4/51
|
1.6%
2/125
|
5.7%
6/106
|
9.8%
5/51
|
|
Infections and infestations
Hepatitis C
|
0.94%
1/106
|
3.9%
2/51
|
2.4%
3/125
|
0.94%
1/106
|
5.9%
3/51
|
|
Infections and infestations
Influenza
|
1.9%
2/106
|
5.9%
3/51
|
0.00%
0/125
|
1.9%
2/106
|
5.9%
3/51
|
|
Infections and infestations
Nasopharyngitis
|
4.7%
5/106
|
9.8%
5/51
|
3.2%
4/125
|
5.7%
6/106
|
9.8%
5/51
|
|
Infections and infestations
Urinary tract infection
|
3.8%
4/106
|
3.9%
2/51
|
3.2%
4/125
|
3.8%
4/106
|
7.8%
4/51
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
1.9%
2/106
|
11.8%
6/51
|
1.6%
2/125
|
1.9%
2/106
|
13.7%
7/51
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
5.7%
6/106
|
7.8%
4/51
|
2.4%
3/125
|
6.6%
7/106
|
9.8%
5/51
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
0.00%
0/106
|
5.9%
3/51
|
0.80%
1/125
|
0.00%
0/106
|
5.9%
3/51
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.9%
2/106
|
5.9%
3/51
|
0.00%
0/125
|
1.9%
2/106
|
9.8%
5/51
|
|
Renal and urinary disorders
Renal failure
|
0.94%
1/106
|
2.0%
1/51
|
8.0%
10/125
|
1.9%
2/106
|
2.0%
1/51
|
|
Vascular disorders
Hypertension
|
7.5%
8/106
|
3.9%
2/51
|
4.0%
5/125
|
8.5%
9/106
|
3.9%
2/51
|
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 or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER