Trial Outcomes & Findings for Advancing Renal TRANSplant eFficacy and Safety Outcomes With an eveRolimus-based regiMen (TRANSFORM) (NCT NCT01950819)

NCT ID: NCT01950819

Last Updated: 2019-01-30

Results Overview

Incidence of failure on the composite of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) \< 50 mL/min/1.73m2.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

2037 participants

Primary outcome timeframe

Month 12 is Primary, Month 24 secondary

Results posted on

2019-01-30

Participant Flow

The full analysis set consisted of all randomized and transplanted patients. The safet set consisted of all patients who received at least one dose of study drug

2226 patients screened; 2037 patients transplanted and randomized to treatment.

Participant milestones

Participant milestones
Measure	EVR+rCNI Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Overall Study STARTED	1022	1015
Overall Study COMPLETED	893	881
Overall Study NOT COMPLETED	129	134

Reasons for withdrawal

Reasons for withdrawal
Measure	EVR+rCNI Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Overall Study Graft Loss	35	30
Overall Study Death	29	34
Overall Study Subject / Gardian decision	54	51
Overall Study technical problems	2	0
Overall Study Pregnancy	0	2
Overall Study Lost to Follow-up	9	17

Baseline Characteristics

full analysis set

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	EVR+rCNI n=1022 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1015 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).	Total n=2037 Participants Total of all reporting groups
Age, Continuous	48.79 years STANDARD_DEVIATION 14.123 • n=93 Participants • full analysis set	48.75 years STANDARD_DEVIATION 14.515 • n=4 Participants • full analysis set	48.77 years STANDARD_DEVIATION 14.316 • n=27 Participants • full analysis set
Sex: Female, Male Female	312 Participants n=93 Participants • full analysis set	308 Participants n=4 Participants • full analysis set	620 Participants n=27 Participants • full analysis set
Sex: Female, Male Male	710 Participants n=93 Participants • full analysis set	707 Participants n=4 Participants • full analysis set	1417 Participants n=27 Participants • full analysis set
Race/Ethnicity, Customized Hispany or Latino	157 Participants n=93 Participants • full analysis set	132 Participants n=4 Participants • full analysis set	289 Participants n=27 Participants • full analysis set
Race/Ethnicity, Customized not Hispanic or Latino	646 Participants n=93 Participants • full analysis set	661 Participants n=4 Participants • full analysis set	1307 Participants n=27 Participants • full analysis set
Race/Ethnicity, Customized Unknown or not reported	219 Participants n=93 Participants • full analysis set	222 Participants n=4 Participants • full analysis set	441 Participants n=27 Participants • full analysis set
Race/Ethnicity, Customized Caucasian	743 Participants n=93 Participants • full analysis set	735 Participants n=4 Participants • full analysis set	1478 Participants n=27 Participants • full analysis set
Race/Ethnicity, Customized Asian	136 Participants n=93 Participants • full analysis set	157 Participants n=4 Participants • full analysis set	293 Participants n=27 Participants • full analysis set
Race/Ethnicity, Customized Black	43 Participants n=93 Participants • full analysis set	35 Participants n=4 Participants • full analysis set	78 Participants n=27 Participants • full analysis set
Race/Ethnicity, Customized Other	100 Participants n=93 Participants • full analysis set	88 Participants n=4 Participants • full analysis set	188 Participants n=27 Participants • full analysis set

PRIMARY outcome

Timeframe: Month 12 is Primary, Month 24 secondary

Population: full analysis set

Incidence of failure on the composite of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) \< 50 mL/min/1.73m2.

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1022 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1015 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2. month 12	489 Participants	456 Participants
Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2. month 24	489 Participants	443 Participants

SECONDARY outcome

Timeframe: Month 12 and 24

Population: full analysis set

Incidence of failure on the composite of (treated biopsy proven acute rejection (tBPAR), graft loss or death

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1022 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1015 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death month 12	146 Participants	131 Participants
Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death month 24	169 Participants	147 Participants

SECONDARY outcome

Timeframe: Month 12 and 24

Population: full analysis set

Incidence of failure on the composite endpoint of tBPAR, graft loss, death or eGFR \< 50 mL/min/1.73m2

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1022 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1015 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Incidence of Failure on the Composite Endpoint of tBPAR, Graft Loss, Death or eGFR < 50 mL/Min/1.73m2 month 12	497 Participants	466 Participants
Incidence of Failure on the Composite Endpoint of tBPAR, Graft Loss, Death or eGFR < 50 mL/Min/1.73m2 month 24	497 Participants	457 Participants

SECONDARY outcome

Timeframe: Month 12 and 24

Population: full analysis set

Incidence of failure on the composite endpoint of graft loss or death.

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1022 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1015 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Incidence of Failure on the Composite Endpoint of Graft Loss or Death. month 12	51 Participants	54 Participants
Incidence of Failure on the Composite Endpoint of Graft Loss or Death. month 24	67 Participants	65 Participants

SECONDARY outcome

Timeframe: Month 12 and 24

Population: full analysis set

Incidence of death, graft loss, tBPAR (treated biopsy proven acute rejection), BPAR (biopsy proven acute rejection), tAR (treated acute rejection), AR (acute rejection) and humoral rejection (aAMR : active antibody mediated rejection and cAMR: chronic antibody mediated rejection)

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1022 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1015 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection aAMR month 12	73 Participants	61 Participants
Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection aAMR month 24	84 Participants	69 Participants
Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection cAMR month 12	9 Participants	14 Participants
Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection cAMR month 24	13 Participants	18 Participants
Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection deaths month 12	20 Participants	28 Participants
Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection deaths month 24	32 Participants	36 Participants
Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection graft loss month 12	33 Participants	28 Participants
Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection graft loss month 24	37 Participants	32 Participants
Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection tBPAR month 12	107 Participants	91 Participants
Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection tBPAR month 24	118 Participants	98 Participants
Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection BPAR month 12	114 Participants	95 Participants
Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection BPAR month 24	127 Participants	104 Participants
Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection tAR month 12	129 Participants	117 Participants
Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection tAR month 24	145 Participants	126 Participants
Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection AR month 12	147 Participants	133 Participants
Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection AR month 24	167 Participants	144 Participants

SECONDARY outcome

Timeframe: Month 12 and 24

Population: full analysis set

Incidence of eGFR \< 50 mL/min/1.73m2

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1022 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1015 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Incidence of eGFR < 50 mL/Min/1.73m2 month 12	456 Participants	424 Participants
Incidence of eGFR < 50 mL/Min/1.73m2 month 24	474 Participants	423 Participants

SECONDARY outcome

Timeframe: Baseline (week 4), Month 12 and 24

Population: full analysis set

Renal allograft function : mean estimated glomerular filtration rate, eGFR

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1022 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1015 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Renal Allograft Function : Mean Estimated Glomerular Filtration Rate, eGFR baseline (week 4)	53.13 mL/min/1.73m2 Standard Error 0.765	52.25 mL/min/1.73m2 Standard Error 0.684
Renal Allograft Function : Mean Estimated Glomerular Filtration Rate, eGFR month 12	53.29 mL/min/1.73m2 Standard Error 0.698	54.49 mL/min/1.73m2 Standard Error 0.667
Renal Allograft Function : Mean Estimated Glomerular Filtration Rate, eGFR month 24	52.63 mL/min/1.73m2 Standard Error 0.744	54.91 mL/min/1.73m2 Standard Error 0.719

SECONDARY outcome

Timeframe: Month 12 and 24

Population: full analysis set

Rate of change of renal function, as eGFR, calculated using MDRD4 formula (Coresh, 2003) and adjusted by covariates.

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1022 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1015 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Evolution of Renal Function, as eGFR, Over Time by Slope Analysis.	0.0001 mL / min / 1.73m2 / day Standard Error 0.0008	0.0047 mL / min / 1.73m2 / day Standard Error 0.0008

SECONDARY outcome

Timeframe: Month 12 and 24

Population: full analysis set with measure

Mean Renal function as assessed in clinical practice, by ceatinine values. Analysis is done without considering missing values for analysis.

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1022 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1015 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Renal Function Assessed by Creatinine Lab Values screening baseline (creatinine, micromol/L)	590.1 micromol/L Standard Deviation 262.78	601.8 micromol/L Standard Deviation 265.08
Renal Function Assessed by Creatinine Lab Values month 12 (creatinine, micromol/L)	129.8 micromol/L Standard Deviation 49.12	128.6 micromol/L Standard Deviation 50.80
Renal Function Assessed by Creatinine Lab Values month 24 (creatinine, micromol/L)	130.1 micromol/L Standard Deviation 53.54	127.6 micromol/L Standard Deviation 52.50

SECONDARY outcome

Timeframe: Month 12 and 24

Population: full analysis set with measure

Mean Renal function as used in clinical practice, using different formula for calculation of renal function than MDRD4 (our primary efficacy parameter), and other alternate formulae (e.g. CKD-EPI). Analysis is done without considering missing values for analysis.

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1022 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1015 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Renal Function by Alternative Formulae (e.g. CKD-EPI). eGFR Values Reported eGFR (Hoek) baseline (mL/min/1.73m2)	21.38 mL/min/1.73m2 Standard Deviation 14.296	20.10 mL/min/1.73m2 Standard Deviation 12.408
Renal Function by Alternative Formulae (e.g. CKD-EPI). eGFR Values Reported eGFR (Hoek) month 12 (mL/min/1.73m2)	50.08 mL/min/1.73m2 Standard Deviation 14.430	52.00 mL/min/1.73m2 Standard Deviation 14.533
Renal Function by Alternative Formulae (e.g. CKD-EPI). eGFR Values Reported eGFR (Hoek) month 24 (mL/min/1.73m2)	49.86 mL/min/1.73m2 Standard Deviation 14.604	52.75 mL/min/1.73m2 Standard Deviation 15.406
Renal Function by Alternative Formulae (e.g. CKD-EPI). eGFR Values Reported eGFR (MDRD4) baseline (mL/min/1.73m2)	11.79 mL/min/1.73m2 Standard Deviation 8.697	11.56 mL/min/1.73m2 Standard Deviation 8.853
Renal Function by Alternative Formulae (e.g. CKD-EPI). eGFR Values Reported eGFR (MDRD4) month 12 (mL/min/1.73m2)	57.59 mL/min/1.73m2 Standard Deviation 19.685	57.58 mL/min/1.73m2 Standard Deviation 18.768
Renal Function by Alternative Formulae (e.g. CKD-EPI). eGFR Values Reported eGFR (MDRD4) month 24 (mL/min/1.73m2)	58.07 mL/min/1.73m2 Standard Deviation 20.168	58.68 mL/min/1.73m2 Standard Deviation 19.541
Renal Function by Alternative Formulae (e.g. CKD-EPI). eGFR Values Reported eGFR-CKDEPI baseline (mL/min/1.73m2)	11.29 mL/min/1.73m2 Standard Deviation 9.094	11.05 mL/min/1.73m2 Standard Deviation 9.195
Renal Function by Alternative Formulae (e.g. CKD-EPI). eGFR Values Reported eGFR-CKDEPI month 12(mL/min/1.73m2)	58.83 mL/min/1.73m2 Standard Deviation 20.686	58.75 mL/min/1.73m2 Standard Deviation 19.757
Renal Function by Alternative Formulae (e.g. CKD-EPI). eGFR Values Reported eGFR-CKDEPI month 24 (mL/min/1.73m2)	59.39 mL/min/1.73m2 Standard Deviation 21.077	59.95 mL/min/1.73m2 Standard Deviation 20.652

SECONDARY outcome

Timeframe: Month 24

Population: safety set 24 months analysis

Incidence of adverse events, serious adverse events and adverse events leading to study regimen discontinuation.

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1014 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1012 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Incidence of Adverse Events, Serious Adverse Events and Adverse Events Leading to Study Regimen Discontinuation.	276 Participants	152 Participants

SECONDARY outcome

Timeframe: Month 24

Population: safety set

Incidence of cytomegalovirus and BK virus, new onset diabetes mellitus, chronic kidney disease with associated proteinuria and calcineurin inhibitor associated adverse events.

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1014 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1012 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Incidence of Cytomegalovirus and BK Virus, New Onset Diabetes Mellitus, Chronic Kidney Disease With Associated Proteinuria and Calcineurin Inhibitor Associated Adverse Events. clinical signs of CMV infection	53 Participants	132 Participants
Incidence of Cytomegalovirus and BK Virus, New Onset Diabetes Mellitus, Chronic Kidney Disease With Associated Proteinuria and Calcineurin Inhibitor Associated Adverse Events. any BKV infection	103 Participants	154 Participants
Incidence of Cytomegalovirus and BK Virus, New Onset Diabetes Mellitus, Chronic Kidney Disease With Associated Proteinuria and Calcineurin Inhibitor Associated Adverse Events. new onset of diabetes mellitus	144 Participants	138 Participants
Incidence of Cytomegalovirus and BK Virus, New Onset Diabetes Mellitus, Chronic Kidney Disease With Associated Proteinuria and Calcineurin Inhibitor Associated Adverse Events. at least one event of interest	871 Participants	764 Participants

SECONDARY outcome

Timeframe: Baseline, Month 12 and 24

Population: safety set with measure

Mean urinary protein and albumin excretion by treatment estimated by mean urinary protein/creatinine and urinary albumin/creatinine ratios.

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1014 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1012 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Urinary Protein and Albumin Excretion by Treatment Estimated by Urinary Protein/Creatinine and Urinary Albumin/Creatinine Ratios. albumine /creatinine ratio baseline	1019.75 mg/g Standard Deviation 2737.96	646.111 mg/g Standard Deviation 799.234
Urinary Protein and Albumin Excretion by Treatment Estimated by Urinary Protein/Creatinine and Urinary Albumin/Creatinine Ratios. albumine /creatinine ratio month 12	150.061 mg/g Standard Deviation 482.394	111.322 mg/g Standard Deviation 444.631
Urinary Protein and Albumin Excretion by Treatment Estimated by Urinary Protein/Creatinine and Urinary Albumin/Creatinine Ratios. albumine /creatinine ratio month 24	149.049 mg/g Standard Deviation 464.470	116.618 mg/g Standard Deviation 433.392
Urinary Protein and Albumin Excretion by Treatment Estimated by Urinary Protein/Creatinine and Urinary Albumin/Creatinine Ratios. protein /creatinine ratio baseline	1648.10 mg/g Standard Deviation 3768.22	1142.59 mg/g Standard Deviation 1003.69
Urinary Protein and Albumin Excretion by Treatment Estimated by Urinary Protein/Creatinine and Urinary Albumin/Creatinine Ratios. protein /creatinine ratio month 12	298.557 mg/g Standard Deviation 642.103	234.698 mg/g Standard Deviation 583.632
Urinary Protein and Albumin Excretion by Treatment Estimated by Urinary Protein/Creatinine and Urinary Albumin/Creatinine Ratios. protein /creatinine ratio month 24	290.242 mg/g Standard Deviation 588.119	233.009 mg/g Standard Deviation 524.383

SECONDARY outcome

Timeframe: Month 24

Population: safety set

Incidence of major cardiovascular events by Preferred Term

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1014 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1012 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Incidence of Major Cardiovascular Events.	66 Participants	86 Participants

SECONDARY outcome

Timeframe: Month 24

Population: safety set

Incidence of malignancies.

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1014 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1012 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Incidence of Malignancies.	41 Participants	39 Participants

SECONDARY outcome

Timeframe: Month 12 and 24

Population: compliance set

Incidence of failure on the composite of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) \< 50 mL/min/1.73m2 among compliant subjects.

Outcome measures

Outcome measures
Measure	EVR+rCNI n=187 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=277 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2 Among Compliant Subjects. month 12	60 Participants	106 Participants
Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2 Among Compliant Subjects. month 24	62 Participants	102 Participants

SECONDARY outcome

Timeframe: Month 12 and 24

Population: full analysis set

Incidence tBPAR, defined as any condition where the subject received anti-rejection treatment and was histologically diagnosed as acute rejection (according to the Banff 2009 criteria), by severity (grade IA, IB, IIA, IIB, III) and time to event. Grades for T-cell mediated rejection, with increasing severity: * Type IA - Significant interstitial infiltration (\> 25% of parenchyma) and foci of moderate tubulitis (\> 4 mononuclear cells/tubular cross section or group of 10 tubular cells). * Type IB - Significant interstitial infiltration (\> 25% of parenchyma) and foci of severe tubulitis (\> 10 mononuclear cells/tubular cross section or group of 10 tubular cells). * Type IIA - Mild to moderate intimal arteritis * Type IIB - Severe intimal arteritis comprising \> 25% of the lumenal area * Type III - Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation)

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1022 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1015 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Participants) Patient's maximum tBPAR grade : no grade (missing)	25 Participants	18 Participants
Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Participants) Patient's maximum tBPAR grade : grade IA	34 Participants	36 Participants
Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Participants) Patient's maximum tBPAR grade : grade IB	23 Participants	17 Participants
Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Participants) Patient's maximum tBPAR grade : grade IIA	21 Participants	24 Participants
Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Participants) Patient's maximum tBPAR grade : grade IIB	9 Participants	3 Participants
Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Participants) Patient's maximum tBPAR grade : grade III	6 Participants	0 Participants

SECONDARY outcome

Timeframe: Month 12 and 24

Population: full analysis set

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1022 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1015 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Events) overall number of tBPAR regardless of grade	146 events	116 events
Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Events) number of tBPAR regardless of grade days 1-90	72 events	63 events
Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Events) number of tBPAR regardless of grade days 91-180	24 events	14 events
Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Events) number of tBPAR regardless of grade days 181-360	25 events	20 events
Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Events) number of tBPAR regardless of grade days 361-540	12 events	15 events
Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Events) number of tBPAR regardless of grade days 541-720	11 events	2 events
Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Events) number of tBPAR regardless of grade days 721-810	2 events	2 events

SECONDARY outcome

Timeframe: Month 12 and 24

Population: full analysis set

Incidence of tBPAR, defined as any condition where the subject received anti-rejection treatment and was histologically diagnosed as acute rejection (according to the Banff 2009 criteria), excluding grade IA rejections. Grades for T-cell mediated rejection, with increasing severity: * Type IA - Significant interstitial infiltration (\> 25% of parenchyma) and foci of moderate tubulitis (\> 4 mononuclear cells/tubular cross section or group of 10 tubular cells). * Type IB - Significant interstitial infiltration (\> 25% of parenchyma) and foci of severe tubulitis (\> 10 mononuclear cells/tubular cross section or group of 10 tubular cells). * Type IIA - Mild to moderate intimal arteritis * Type IIB - Severe intimal arteritis comprising \> 25% of the lumenal area * Type III - Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation)

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1022 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1015 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Incidence of tBPAR (Treated Biopsy-proven Acute Rejection) Excluding Grade IA Rejections month 12	66 Participants	53 Participants
Incidence of tBPAR (Treated Biopsy-proven Acute Rejection) Excluding Grade IA Rejections month 24	74 Participants	55 Participants

SECONDARY outcome

Timeframe: Month 12 and 24

Population: full analysis set

Incidence of composite of tBPAR or eGRF\<50 mL/min/1.73m2 by subgroup

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1022 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1015 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Incidence of Composite of tBPAR (Treated Biopsy-proven Acute Rejection)or eGRF<50 mL/Min/1.73m2 by Subgroup month 12	489 Participants	456 Participants
Incidence of Composite of tBPAR (Treated Biopsy-proven Acute Rejection)or eGRF<50 mL/Min/1.73m2 by Subgroup month 24	489 Participants	443 Participants

SECONDARY outcome

Timeframe: Month 12 and 24

Population: full analysis set

Incidence of tBPAR (excluding grade IA rejections) or GFR\<50 mL/min/1.73m2

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1022 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1015 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Incidence of tBPAR (Excluding Grade IA Rejections) or GFR<50 mL/Min/1.73m2 month 12	475 Participants	441 Participants
Incidence of tBPAR (Excluding Grade IA Rejections) or GFR<50 mL/Min/1.73m2 month 24	475 Participants	426 Participants

SECONDARY outcome

Timeframe: Month 12 and 24

Population: full analysis set

Incidence of failure on the composite of (treated biopsy proven acute rejection (tBPAR), graft loss or death or loss to follow-up

Outcome measures

Outcome measures
Measure	EVR+rCNI n=1022 Participants Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)	MPA+sCNI n=1015 Participants Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death or Loss to Follow-up month 12	181 Participants	170 Participants
Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death or Loss to Follow-up month 24	218 Participants	201 Participants

Adverse Events

Everolimus Plus@Reduced CNI

Serious events: 593 serious events

Other events: 951 other events

Deaths: 20 deaths

MPA Plus Standard@CNI

Serious events: 613 serious events

Other events: 942 other events

Deaths: 29 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharma

Phone: 8627788300

Email: [email protected]

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 (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Everolimus Plus@Reduced CNI n=1014 participants at risk Everolimus plus@reduced CNI	MPA Plus Standard@CNI n=1012 participants at risk MPA plus standard@CNI
Infections and infestations Pseudomonal bacteraemia	0.00% 0/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.10% 1/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Infections and infestations Pseudomonal sepsis	0.00% 0/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.10% 1/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Infections and infestations Pulmonary tuberculosis	0.20% 2/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.10% 1/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Infections and infestations Pyelonephritis	2.4% 24/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	3.3% 33/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Infections and infestations Pyelonephritis acute	0.59% 6/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	1.3% 13/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Agranulocytosis	0.20% 2/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Anaemia	1.4% 14/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.59% 6/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Atypical haemolytic uraemic syndrome	0.10% 1/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Bone marrow failure	0.00% 0/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.10% 1/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.49% 5/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Granulocytopenia	0.00% 0/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.10% 1/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Haemolysis	0.20% 2/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Haemolytic uraemic syndrome	0.10% 1/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.20% 2/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.10% 1/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Leukocytosis	0.10% 1/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Leukopenia	0.39% 4/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	1.2% 12/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Lymphadenopathy	0.10% 1/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Lymphatic obstruction	0.10% 1/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.10% 1/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Nephrogenic anaemia	0.00% 0/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.10% 1/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Neutropenia	0.10% 1/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.59% 6/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Pancytopenia	0.20% 2/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.10% 1/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Polycythaemia	0.00% 0/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.20% 2/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Sickle cell anaemia with crisis	0.10% 1/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Splenomegaly	0.00% 0/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.10% 1/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Thrombocytopenia	0.30% 3/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.10% 1/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Thrombotic microangiopathy	0.79% 8/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.30% 3/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Acute coronary syndrome	0.39% 4/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.20% 2/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Acute myocardial infarction	0.59% 6/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.59% 6/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Angina pectoris	0.59% 6/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.49% 5/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Angina unstable	0.10% 1/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.10% 1/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Aortic valve stenosis	0.00% 0/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.10% 1/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Arrhythmia	0.00% 0/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.10% 1/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Arrhythmia supraventricular	0.10% 1/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.20% 2/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Atrial fibrillation	1.2% 12/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	1.2% 12/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Atrial flutter	0.39% 4/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.10% 1/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Bradycardia	0.30% 3/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.10% 1/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Cardiac arrest	0.39% 4/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.40% 4/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Cardiac asthma	0.00% 0/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.10% 1/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.

Other adverse events
Measure	Everolimus Plus@Reduced CNI n=1014 participants at risk Everolimus plus@reduced CNI	MPA Plus Standard@CNI n=1012 participants at risk MPA plus standard@CNI
Blood and lymphatic system disorders Anaemia	22.4% 227/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	23.5% 238/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Leukocytosis	2.4% 24/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	5.7% 58/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Leukopenia	9.3% 94/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	19.2% 194/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Polycythaemia	5.1% 52/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	4.2% 42/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Thrombocytopenia	7.3% 74/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	4.1% 41/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Tachycardia	5.2% 53/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	5.1% 52/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Abdominal pain	9.3% 94/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	10.3% 104/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Abdominal pain upper	3.8% 39/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	6.1% 62/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Constipation	24.2% 245/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	23.9% 242/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Diarrhoea	23.9% 242/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	31.4% 318/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Nausea	18.8% 191/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	22.2% 225/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Vomiting	11.8% 120/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	13.8% 140/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Fatigue	5.8% 59/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	6.3% 64/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Oedema peripheral	34.2% 347/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	24.1% 244/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Pyrexia	11.0% 112/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	13.0% 132/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Infections and infestations BK virus infection	5.5% 56/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	10.0% 101/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Infections and infestations Cytomegalovirus infection	2.4% 24/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	9.2% 93/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Infections and infestations Nasopharyngitis	10.8% 110/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	11.6% 117/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Infections and infestations Upper respiratory tract infection	8.0% 81/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	10.1% 102/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Infections and infestations Urinary tract infection	21.6% 219/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	24.6% 249/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Injury, poisoning and procedural complications Complications of transplanted kidney	6.2% 63/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	5.3% 54/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Injury, poisoning and procedural complications Incision site pain	5.0% 51/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	6.0% 61/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Injury, poisoning and procedural complications Procedural pain	8.9% 90/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	9.8% 99/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Investigations Blood creatinine increased	13.9% 141/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	13.1% 133/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Investigations Weight increased	3.7% 38/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	6.5% 66/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Diabetes mellitus	13.1% 133/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	11.9% 120/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Dyslipidaemia	9.7% 98/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	5.6% 57/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Hypercalcaemia	3.8% 39/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	6.6% 67/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Hypercholesterolaemia	10.2% 103/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	6.0% 61/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Hyperglycaemia	13.8% 140/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	14.2% 144/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Hyperkalaemia	16.2% 164/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	18.2% 184/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Hyperlipidaemia	13.3% 135/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	7.4% 75/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Hypertriglyceridaemia	5.7% 58/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	2.4% 24/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Hyperuricaemia	4.8% 49/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	6.3% 64/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Hypocalcaemia	10.7% 109/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	9.7% 98/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Hypokalaemia	14.6% 148/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	8.6% 87/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Hypomagnesaemia	13.2% 134/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	16.6% 168/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Hypophosphataemia	18.7% 190/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	16.5% 167/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Metabolic acidosis	7.6% 77/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	9.7% 98/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Vitamin D deficiency	5.2% 53/1014 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	5.6% 57/1012 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years. treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.