Trial Outcomes & Findings for Efficacy of Everolimus as Inhibitor of Fibrosis Progression in Liver Transplant Patients With Recurrence of Hepatitis C Viral Infection (NCT NCT00582738)

Last Updated: 2012-09-06

Results Overview

Ishak-Knodell Score: 0=No fibrosis; 01=Fibrous expansion of some portal areas, with or without short fibrous septa; 02=Fibrous expansion of most portal areas, with or without short fibrous septa; 03=Fibrous expansion of most portal areas, with occasional portal to portal (P-P) bridging; 04=Fibrous expansion of portal areas, with marked bridging (portal to portal (P-P) as well as portal to central (P-C)); 05=Marked bridging (P-P and/or P-C) with occasional nodules (incomplete cirrhosis); 06=Cirrhosis, probable or definite Decrease in score from baseline indicates improvement

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

43 participants

Primary outcome timeframe

baseline, 24 Months

Results posted on

2012-09-06

Participant Flow

Participant milestones

Participant milestones
Measure	Standard Treatment Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Overall Study STARTED	21	22
Overall Study COMPLETED	12	4
Overall Study NOT COMPLETED	9	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Standard Treatment Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Overall Study Administrative Problems	7	8
Overall Study Adverse Event	0	5
Overall Study Graft Lost	0	1
Overall Study Other	1	0
Overall Study Protocol Violation	1	1
Overall Study Withdrawal by Subject	0	3

Baseline Characteristics

Efficacy of Everolimus as Inhibitor of Fibrosis Progression in Liver Transplant Patients With Recurrence of Hepatitis C Viral Infection

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard Treatment n=21 Participants Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus n=22 Participants Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.	Total n=43 Participants Total of all reporting groups
Age Continuous	60.0 years FULL_RANGE 6.79 • n=5 Participants	56.5 years FULL_RANGE 8.01 • n=7 Participants	57 years n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	15 Participants n=7 Participants	26 Participants n=5 Participants

PRIMARY outcome

Timeframe: baseline, 24 Months

Population: The Intent to Treat (ITT) population consisted of all patients randomized and who had at least one dose of study medication. Small number of biopsies obtained at Month 24 due to study being prematurely terminated.

Outcome measures

Outcome measures
Measure	CsA-TAC n=8 Participants Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus n=5 Participants Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.	Standard Treatment -Summary of Fibrotest by Treatment Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus - Summary of Fibrotest by Treatment Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Change From Baseline in Fibrosis Staging Score (Measured by the Ishak-Knodell Staging Score) Between Baseline and 24 Months Post-transplant.	-0.5 Score on Scale Full Range 1.20 • Interval -1.0 to 2.0	0.0 Score on Scale Full Range 0.45 • Interval -1.0 to 0.0	—	—

SECONDARY outcome

Timeframe: Baseline, 12 months, 24 months

Population: The Intent to Treat (ITT) population consisted of all patients randomized and who had at least one dose of study medication. Only participants with observations at baseline and specified timepoints were included in the analysis.

Metavir Score: F0=No fibrosis; F1=Portal fibrosis without septa; F2=Portal fibrosis with rare septa; F3=Numerous septa without cirrhosis Decrease in score from baseline indicates improvement

Outcome measures

Outcome measures
Measure	CsA-TAC n=18 Participants Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus n=14 Participants Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.	Standard Treatment -Summary of Fibrotest by Treatment Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus - Summary of Fibrotest by Treatment Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization Month 12-Baseline (n=18, 14)	0.0 Scores on a Scale Full Range 0.76 • Interval -1.0 to 2.0	0.0 Scores on a Scale Full Range 0.85 • Interval -2.0 to 1.0	—	—
Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization Baseline (n=18, 14)	1.0 Scores on a Scale Full Range 0.84 • Interval 1.0 to 4.0	1.5 Scores on a Scale Full Range 0.83 • Interval 1.0 to 3.0	—	—
Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization Month 12 (n=18, 14)	1.0 Scores on a Scale Full Range 1.04 • Interval 0.0 to 4.0	1.0 Scores on a Scale Full Range 0.80 • Interval 0.0 to 3.0	—	—
Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization Month 24 (n=8, 5)	1.0 Scores on a Scale Full Range 1.04 • Interval 0.0 to 3.0	1.0 Scores on a Scale Full Range 0.89 • Interval 1.0 to 3.0	—	—
Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization Month 24-Baseline (n=8, 5)	0.0 Scores on a Scale Interval -1.0 to 2.0	0.0 Scores on a Scale Interval -1.0 to 0.0	—	—

SECONDARY outcome

Timeframe: 24 Months

Population: The Intent to Treat (ITT) population consisted of all patients randomized and who had at least one dose of study medication.

Outcome measures

Outcome measures
Measure	CsA-TAC n=21 Participants Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus n=22 Participants Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.	Standard Treatment -Summary of Fibrotest by Treatment Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus - Summary of Fibrotest by Treatment Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Percentage of Patients With Death, Graft Loss and Biopsy Proven Acute Rejection (BPAR) Between Study Groups Death	0 Percentage of Participants	4.5 Percentage of Participants	—	—
Percentage of Patients With Death, Graft Loss and Biopsy Proven Acute Rejection (BPAR) Between Study Groups Graft Loss	0 Percentage of Participants	4.5 Percentage of Participants	—	—
Percentage of Patients With Death, Graft Loss and Biopsy Proven Acute Rejection (BPAR) Between Study Groups Acute Rejection (BPAR)	0 Percentage of Participants	0.0 Percentage of Participants	—	—

SECONDARY outcome

Timeframe: 12 months, 24 months

Population: The Intent to Treat (ITT) population consisted of all patients randomized and who had at least one dose of study medication. During different time points, participants with observations at that time point were included in the analysis.

Outcome measures

Outcome measures
Measure	CsA-TAC n=21 Participants Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus n=22 Participants Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.	Standard Treatment -Summary of Fibrotest by Treatment Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus - Summary of Fibrotest by Treatment Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Number of Patients With Events (Progression to Cirrhosis, Retransplantation, HCV Related Death, First BPAR, Graft Loss)at 12 and 24 Months 12 months	0 participants	0 participants	—	—
Number of Patients With Events (Progression to Cirrhosis, Retransplantation, HCV Related Death, First BPAR, Graft Loss)at 12 and 24 Months 24 months	0 participants	1 participants	—	—

SECONDARY outcome

Timeframe: 12 months, 24 months/EOS

Population: The Intent to Treat (ITT) population consists of all patients randomized and who have at least one dose of study medication. During different time points, participants with observations at that time point were included in the analysis.

GFR Month 9 value if available, otherwise minimal first year post-randomization available value. Imputation rule of missing Month 24 GFR values: GFR Month 18 value if available, otherwise Month 12 GFR is used. Least square means are from an ANCOVA model containing treatment as factor and baseline eGFR as a covariate.

Outcome measures

Outcome measures
Measure	CsA-TAC n=21 Participants Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus n=22 Participants Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.	Standard Treatment -Summary of Fibrotest by Treatment Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus - Summary of Fibrotest by Treatment Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Comparison of Renal Function (Glomerular Filtration Rate [GFR] Calculated Using the Modification of Diet in Renal Disease Study Group [MDRD] Formula) Between Study Groups 12 Months (n=21, 22)	62.2 mL/min/1.73^2 Standard Error 2.95	65.6 mL/min/1.73^2 Standard Error 2.88	—	—
Comparison of Renal Function (Glomerular Filtration Rate [GFR] Calculated Using the Modification of Diet in Renal Disease Study Group [MDRD] Formula) Between Study Groups 24 months (n=20, 18)	65.5 mL/min/1.73^2 Standard Error 2.51	71.6 mL/min/1.73^2 Standard Error 2.65	—	—

SECONDARY outcome

Timeframe: baseline, 12 months, 24 months

Outcome measures

Outcome measures
Measure	CsA-TAC n=18 Participants Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus n=14 Participants Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.	Standard Treatment -Summary of Fibrotest by Treatment Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus - Summary of Fibrotest by Treatment Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Comparison of the Effect of Both Regimens in the Necroinflammatory Grading Score (Ishak-Knodell) (Portal Inflammation) Baseline (n= 18, 14)	1.8 Score on a scale Standard Deviation 1.04	2.4 Score on a scale Standard Deviation .93	—	—
Comparison of the Effect of Both Regimens in the Necroinflammatory Grading Score (Ishak-Knodell) (Portal Inflammation) Month 12 (n = 18, 14)	1.9 Score on a scale Standard Deviation 1.02	1.9 Score on a scale Standard Deviation 1.00	—	—
Comparison of the Effect of Both Regimens in the Necroinflammatory Grading Score (Ishak-Knodell) (Portal Inflammation) Month 24 (n = 8, 5)	2.1 Score on a scale Standard Deviation 0.35	2.0 Score on a scale Standard Deviation 0.71	—	—

SECONDARY outcome

Timeframe: baseline, 12 and 24 months

The Fibrosure test is the combination of Fibro-test + Acti-test. FibroTest (FT) was for the assessment of fibrosis. Fibro test was calculated using an original combination of five highly concentrated serum biochemical markers; alpha2macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin and gammaglutamyltransferase (GGT). FibroTest scores range from 0.00 to 1.00 where 0.0-0.21 is no fibrosis and \>= 0.59 is cirrhosis. Acti-test was calculated using 6 serum biochemical markers; alpha2macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin, GGT and alanine aminotransferase (ALT). ActiTest (AT) was used for the assessment of necroinflammatory activity. Test score ranges from 0.00 to 1.00, where 0.00-0.17 indicates no necrosis and \>= 0.61 indicates severe necrosis If 12-month Actitest value was the last available assessment, the value is used to impute the final staging score(End of Study)

Outcome measures

Outcome measures
Measure	CsA-TAC n=21 Participants Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus n=22 Participants Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.	Standard Treatment -Summary of Fibrotest by Treatment n=21 Participants Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus - Summary of Fibrotest by Treatment n=21 Participants Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry Baseline (n=21,21,21,21)	0.40 units on a scale Full Range .30 • Interval 0.1 to 0.9	0.50 units on a scale Full Range .25 • Interval 0.2 to 1.0	0.80 units on a scale Full Range .18 • Interval 0.4 to 1.0	0.80 units on a scale Full Range .13 • Interval 0.5 to 1.0
Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry month 12 (n=20,17, 20, 17)	0.60 units on a scale Full Range .28 • Interval 0.0 to 0.9	0.50 units on a scale Full Range .23 • Interval 0.2 to 1.0	0.80 units on a scale Full Range .16 • Interval 0.4 to 1.0	0.80 units on a scale Full Range .15 • Interval 0.4 to 1.0
Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry month 24 (n=1,2,1,2)	0.60 units on a scale Full Range 0.0 • Interval 0.6 to 0.6	0.70 units on a scale Full Range .33 • Interval 0.4 to 0.9	0.90 units on a scale Full Range 0.0 • Interval 0.9 to 0.9	1.0 units on a scale Full Range .04 • Interval 0.9 to 1.0
Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry end of study [month 24] (n=20,21,20,21)	0.60 units on a scale Full Range .32 • Interval 0.1 to 0.9	0.50 units on a scale Full Range .26 • Interval 0.1 to 1.0	0.80 units on a scale Full Range .15 • Interval 0.5 to 1.0	0.70 units on a scale Full Range .17 • Interval 0.5 to 1.0

SECONDARY outcome

Timeframe: baseline to month 24

Population: Difference Ishak-Knodell Score at End-of-Study The Intent to Treat (ITT) population consists of all patients randomized and who have at least one dose of study medication

Outcome measures

Outcome measures
Measure	CsA-TAC n=21 Participants Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus n=22 Participants Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.	Standard Treatment -Summary of Fibrotest by Treatment Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus - Summary of Fibrotest by Treatment Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Percentage of Patients in Each Study Arm With Increase of ≥1 Point in the Ishak-Knodell Staging Score in Fibrosis	38.9 percentage of participants	7.1 percentage of participants	—	—

SECONDARY outcome

Timeframe: baseline, 12 months, 24 months/EOS

Population: The Intent to Treat (ITT) population consists of all patients randomized and who have at least one dose of study medication. If 12-month HCV was the last available assessment, this value is used to impute the End of Study value.

End of Study (EOS) endpoint is the last available assessment on or after Month 12. A reduction of at least two logs in HCV RNA viral load was considered as success

Outcome measures

Outcome measures
Measure	CsA-TAC n=20 Participants Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus n=20 Participants Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.	Standard Treatment -Summary of Fibrotest by Treatment Continuation of current immunosuppressive regimen (continuation of Calcineurin Inhibitor \[CNI\] with or without Enteric-coated mycophenolate sodium (myfortic) or mycophenolate mofetil(Cellcept)\[MPA\], with or without steroids) / no everolimus introduction.	Everolimus - Summary of Fibrotest by Treatment Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization baseline	6.6 log10 copies/ml Standard Deviation 0.69	6.4 log10 copies/ml Standard Deviation 0.94	—	—
Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization 12 months (n=20, 20)	6.5 log10 copies/ml Standard Deviation 0.84	6.6 log10 copies/ml Standard Deviation .85	—	—
Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization 24 months/EoS (n=20, 20)	6.9 log10 copies/ml Standard Deviation 0.69	6.7 log10 copies/ml Standard Deviation 0.87	—	—
Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization Month 12 - baseline (n=20,20)	-0.1 log10 copies/ml Standard Deviation 0.71	0.2 log10 copies/ml Standard Deviation 0.72	—	—
Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization Monh 24 - baseline (n=20,20)	0.3 log10 copies/ml Standard Deviation 0.76	0.3 log10 copies/ml Standard Deviation 0.84	—	—

Adverse Events

CsA/TAC

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

EVR (Everolimus)

Serious events: 11 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	CsA/TAC n=21 participants at risk Continuation of current immunosuppressive regimen (continuation of CNI with or without MPA, with or without steroids) / no everolimus introduction.	EVR (Everolimus) n=22 participants at risk Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/21	4.5% 1/22
Cardiac disorders Tachyarrhythmia	0.00% 0/21	4.5% 1/22
Gastrointestinal disorders Abdominal hernia	0.00% 0/21	4.5% 1/22
Gastrointestinal disorders Ascites	0.00% 0/21	4.5% 1/22
Hepatobiliary disorders Cholangitis	0.00% 0/21	4.5% 1/22
Infections and infestations Gastroenteritis	0.00% 0/21	4.5% 1/22
Infections and infestations Hepatitis C	0.00% 0/21	4.5% 1/22
Infections and infestations Pneumonia	0.00% 0/21	4.5% 1/22
Infections and infestations Sepsis	0.00% 0/21	4.5% 1/22
Infections and infestations Wound infection	0.00% 0/21	4.5% 1/22
Injury, poisoning and procedural complications Hepatic haematoma	0.00% 0/21	4.5% 1/22
Investigations Transaminases increased	0.00% 0/21	4.5% 1/22
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/21	4.5% 1/22
Nervous system disorders Ischaemic stroke	0.00% 0/21	4.5% 1/22
Renal and urinary disorders Renal failure	0.00% 0/21	4.5% 1/22
Reproductive system and breast disorders Erectile dysfunction	0.00% 0/21	4.5% 1/22
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/21	4.5% 1/22
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/21	4.5% 1/22
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	0.00% 0/21	4.5% 1/22

Other adverse events

Other adverse events
Measure	CsA/TAC n=21 participants at risk Continuation of current immunosuppressive regimen (continuation of CNI with or without MPA, with or without steroids) / no everolimus introduction.	EVR (Everolimus) n=22 participants at risk Initiation of everolimus with discontinuation of CNI/MPA, with or without steroids.
Blood and lymphatic system disorders Leukopenia	4.8% 1/21	9.1% 2/22
Gastrointestinal disorders Aphthous stomatitis	0.00% 0/21	18.2% 4/22
Gastrointestinal disorders Diarrhoea	0.00% 0/21	18.2% 4/22
Gastrointestinal disorders Mouth ulceration	4.8% 1/21	9.1% 2/22
Gastrointestinal disorders Stomatitis	0.00% 0/21	9.1% 2/22
General disorders Pyrexia	0.00% 0/21	13.6% 3/22
Hepatobiliary disorders Cholelithiasis	0.00% 0/21	9.1% 2/22
Infections and infestations Bronchitis	0.00% 0/21	9.1% 2/22
Infections and infestations Influenza	4.8% 1/21	9.1% 2/22
Infections and infestations Upper respiratory tract infection	0.00% 0/21	9.1% 2/22
Investigations Blood cholesterol increased	9.5% 2/21	13.6% 3/22
Investigations Blood triglycerides increased	9.5% 2/21	4.5% 1/22
Investigations Blood uric acid abnormal	9.5% 2/21	0.00% 0/22
Investigations Blood uric acid increased	9.5% 2/21	0.00% 0/22
Investigations Liver function test abnormal	0.00% 0/21	18.2% 4/22
Investigations Platelet count decreased	0.00% 0/21	13.6% 3/22
Metabolism and nutrition disorders Dyslipidaemia	0.00% 0/21	13.6% 3/22
Metabolism and nutrition disorders Hyperglycaemia	9.5% 2/21	13.6% 3/22
Metabolism and nutrition disorders Hypertriglyceridaemia	9.5% 2/21	13.6% 3/22
Renal and urinary disorders Proteinuria	9.5% 2/21	9.1% 2/22
Renal and urinary disorders Renal impairment	19.0% 4/21	0.00% 0/22
Skin and subcutaneous tissue disorders Erythema	0.00% 0/21	13.6% 3/22
Skin and subcutaneous tissue disorders Pruritus	4.8% 1/21	22.7% 5/22
Vascular disorders Hypertension	4.8% 1/21	9.1% 2/22

Additional Information

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