Extension Study to Evaluate the Long-term Efficacy and Sa... | NCT01150097

ID	Type	Description	Link
2009-017311-15

Label	Type	Description	Intervention Names
Everolimus + reduced tacrolimus	Experimental	Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.	Drug: Tacrolimus (reduced tacrolimus) Drug: Everolimus (reduced tacrolimus) Drug: Corticosteroids
Tacrolimus elimination	Experimental	Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.	Drug: Tacrolimus (tacrolimus elimination) Drug: Everolimus (tacrolimus elimination) Drug: Corticosteroids
Tacrolimus control	Active Comparator	Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.	Drug: Tacrolimus (tacrolimus control) Drug: Corticosteroids

Name	Type	Description	Arm Group Labels	Other Names
Tacrolimus (reduced tacrolimus)	Drug	After everolimus whole blood trough levels were confirmed to be in the target range of 3-8 ng/mL, tacrolimus tapering began, achieving a target tacrolimus whole blood trough level of 3-5 ng/mL by 3 weeks after randomization, a level which was maintained for the duration of the study.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Incidence Rate of Composite Efficacy Failure Defined as Treated Biopsy Proven Acute Rejection (tBPAR ), Graft Loss or Death	The number of participants who experienced composite efficacy failure was analyzed. Composite efficacy failure was defined as treated biopsy proven acute rejection (tBPAR), graft loss, or death. A BPAR was defined as an acute rejection confirmed by biopsy with a Rejection Activity Index (RAI) score ≥ 3. tBPAR was defined as a BPAR which was treated with anti-rejection therapy. The RAI is used to score liver biopsies with acute rejection and is composed of 3 categories (portal inflammation, bile duct inflammation damage, and venous endothelial inflammation) each scored on a scale of 0 (absent) to 3 (severe) by a trained pathologist. The total RAI score = the sum of the scores of the 3 categories and ranges from 0 to 9, with a higher score indicating greater rejection. The graft was presumed to be lost on the day the patient was newly listed for a liver graft, received a graft re-transplant, or died.	from months 24 to 36
Incidence Rate of Composite Efficacy Failure Defined as Treated Biopsy Proven Acute Rejection (tBPAR ), Graft Loss or Death	The number of participants who experienced composite efficacy failure was analyzed. Composite efficacy failure was defined as treated biopsy proven acute rejection (tBPAR), graft loss, or death. A BPAR was defined as an acute rejection confirmed by biopsy with a Rejection Activity Index (RAI) score ≥ 3. tBPAR was defined as a BPAR which was treated with anti-rejection therapy. The RAI is used to score liver biopsies with acute rejection and is composed of 3 categories (portal inflammation, bile duct inflammation damage, and venous endothelial inflammation) each scored on a scale of 0 (absent) to 3 (severe) by a trained pathologist. The total RAI score = the sum of the scores of the 3 categories and ranges from 0 to 9, with a higher score indicating greater rejection. The graft was presumed to be lost on the day the patient was newly listed for a liver graft, received a graft re-transplant, or died.	from months 36 to 48
Incidence Rate of Composite Efficacy Failure Defined as Graft Loss or Death	The number of participants who experienced graft loss or death was analyzed. The graft was presumed to be lost on the day the patient was newly listed for a liver graft, received a graft re-transplant, or died.

Secondary Outcomes

Measure	Description	Time Frame
Incidence Rate of tBPAR	The number of participants who had a tBPAR was analyzed. tBPAR was defined as a BPAR which was treated with anti-rejection therapy. The RAI is used to score liver biopsies with acute rejection and is composed of 3 categories (portal inflammation, bile duct inflammation damage, and venous endothelial inflammation) each scored on a scale of 0 (absent) to 3 (severe) by a trained pathologist. The total RAI score = the sum of the scores of the 3 categories and ranges from 0 to 9, with a higher score indicating greater rejection.

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Washington D.C.	District of Columbia	20007-2197	United States
Novartis Investigative Site

ID	Title	Description
FG000	Everolimus + Reduced Tacrolimus	Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
FG001	Tacrolimus Elimination

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Incidence Rate of Composite Efficacy Failure Defined as Treated Biopsy Proven Acute Rejection (tBPAR ), Graft Loss or Death

The number of participants who experienced composite efficacy failure was analyzed. Composite efficacy failure was defined as treated biopsy proven acute rejection (tBPAR), graft loss, or death. A BPAR was defined as an acute rejection confirmed by biopsy with a Rejection Activity Index (RAI) score ≥ 3. tBPAR was defined as a BPAR which was treated with anti-rejection therapy. The RAI is used to score liver biopsies with acute rejection and is composed of 3 categories (portal inflammation, bile duct inflammation damage, and venous endothelial inflammation) each scored on a scale of 0 (absent) to 3 (severe) by a trained pathologist. The total RAI score = the sum of the scores of the 3 categories and ranges from 0 to 9, with a higher score indicating greater rejection. The graft was presumed to be lost on the day the patient was newly listed for a liver graft, received a graft re-transplant, or died.

All extension participants

Posted

Number

Participants

from months 24 to 36

ID	Title	Description
OG000	Everolimus + Reduced Tacrolimus	Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
OG001	Tacrolimus Elimination	Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
OG002	Tacrolimus Control	Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.

Units	Counts
Participants	OG000106 OG00151 OG002125

Title

Denominators

Categories

Title	Measurements
	OG0002 OG0011 OG0023

Primary

Incidence Rate of Composite Efficacy Failure Defined as Treated Biopsy Proven Acute Rejection (tBPAR ), Graft Loss or Death

Participants from the everolimus + reduced tacrolimus group and the tacrolimus elimination group

Posted

Number

Participants

from months 36 to 48

ID	Title	Description
OG000	Everolimus + Reduced Tacrolimus	Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
OG001	Tacrolimus Elimination	Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.

Primary

Incidence Rate of Composite Efficacy Failure Defined as Graft Loss or Death

The number of participants who experienced graft loss or death was analyzed. The graft was presumed to be lost on the day the patient was newly listed for a liver graft, received a graft re-transplant, or died.

All extension participants

Posted

Number

Participants

from months 24 to 36

ID	Title	Description
OG000	Everolimus + Reduced Tacrolimus	Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
OG001	Tacrolimus Elimination	Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
OG002	Tacrolimus Control	Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.

Units	Counts
Participants

Primary

Incidence Rate of Composite Efficacy Failure Defined as Graft Loss or Death

Participants from the everolimus + reduced tacrolimus group and the tacrolimus elimination group

Posted

Number

Participants

from months 36 - 48

ID	Title	Description
OG000	Everolimus + Reduced Tacrolimus	Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
OG001	Tacrolimus Elimination	Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.

Units	Counts
Participants	OG000

Secondary

Incidence Rate of tBPAR

The number of participants who had a tBPAR was analyzed. tBPAR was defined as a BPAR which was treated with anti-rejection therapy. The RAI is used to score liver biopsies with acute rejection and is composed of 3 categories (portal inflammation, bile duct inflammation damage, and venous endothelial inflammation) each scored on a scale of 0 (absent) to 3 (severe) by a trained pathologist. The total RAI score = the sum of the scores of the 3 categories and ranges from 0 to 9, with a higher score indicating greater rejection.

All extension participants

Posted

Number

Participants

from months 24 - 36

ID	Title	Description
OG000	Everolimus + Reduced Tacrolimus	Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
OG001	Tacrolimus Elimination	Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
OG002	Tacrolimus Control	Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.

Primary

Change in Renal Function

Change in renal function was assessed by the estimated Glomerular Filtration Rate (eGFR) using the abbreviated (4 variables) Modification of Diet in Renal Disease (MDRD-4) formula which was developed by the MDRD Study Group and has been validated in patients with chronic kidney disease. The MDRD-4 formula used for the eGFR calculation is: eGFR (mL/min/1.73m^2) = 186.3*(C^-1.154)*(A^-0.203)*G*R, where C is the serum concentration of creatinine (mg/dL), A is age (years), G=0.742 when gender is female, otherwise G=1, R=1.21 when race is black, otherwise R=1.

The analysis population included extension participants who had both post-extension baseline and month 36 values only.

Posted

Mean

Standard Deviation

mL/min/1.73m^2

from months 24 to 36

ID	Title	Description
OG000	Everolimus + Reduced Tacrolimus	Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
OG001	Tacrolimus Elimination	Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
OG002	Tacrolimus Control	Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG0031 affected106 at risk EG0040 affected51 at risk
Haemolytic uraemic syndrome	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Splenomegaly	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Coronary artery stenosis	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Tachycardia	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Abdominal adhesions	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Abdominal hernia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Abdominal strangulated hernia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0011 affected51 at risk EG0020 affected125 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Crohn's disease	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected106 at risk EG0010 affected51 at risk EG0022 affected125 at risk EG003
Gastrointestinal obstruction	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Hernial eventration	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0022 affected125 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Oesophageal ulcer	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0011 affected51 at risk EG0020 affected125 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Umbilical hernia, obstructive	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0011 affected51 at risk EG0020 affected125 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected106 at risk EG0010 affected51 at risk EG0022 affected125 at risk EG003
Device occlusion	General disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
General physical health deterioration	General disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Generalised oedema	General disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0011 affected51 at risk EG0020 affected125 at risk EG003
Impaired healing	General disorders	MedDRA	Systematic Assessment	EG0002 affected106 at risk EG0011 affected51 at risk EG0020 affected125 at risk EG003
Oedema peripheral	General disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0011 affected51 at risk EG0020 affected125 at risk EG003
Pyrexia	General disorders	MedDRA	Systematic Assessment	EG0003 affected106 at risk EG0012 affected51 at risk EG0022 affected125 at risk EG003
Sudden death	General disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Acute hepatic failure	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Autoimmune hepatitis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Bile duct stenosis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Biliary ischaemia	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Cholangitis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0011 affected51 at risk EG0020 affected125 at risk EG003
Cholestasis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Hepatic artery thrombosis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Hepatic necrosis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Hepatic steatosis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Portal vein thrombosis	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Abdominal sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Arthritis bacterial	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Bacteraemia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0011 affected51 at risk EG0020 affected125 at risk EG003
Bronchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Cellulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Epstein-Barr viraemia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Erysipelas	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0011 affected51 at risk EG0020 affected125 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Haematoma infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Hepatitis C	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Liver abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Localised infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Oral herpes	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Orchitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Paronychia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0011 affected51 at risk EG0020 affected125 at risk EG003
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected106 at risk EG0012 affected51 at risk EG0023 affected125 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0011 affected51 at risk EG0020 affected125 at risk EG003
Sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected106 at risk EG0011 affected51 at risk EG0020 affected125 at risk EG003
Septic shock	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Streptococcal sepsis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0011 affected51 at risk EG0022 affected125 at risk EG003
Viral infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Wound abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Anastomotic stenosis	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Clavicle fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Graft loss	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Incisional hernia	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0012 affected51 at risk EG0021 affected125 at risk EG003
Incisional hernia, obstructive	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Joint dislocation	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0011 affected51 at risk EG0020 affected125 at risk EG003
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0011 affected51 at risk EG0020 affected125 at risk EG003
Overdose	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Post procedural bile leak	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Postoperative hernia	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0011 affected51 at risk EG0020 affected125 at risk EG003
Radius fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Tendon rupture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0011 affected51 at risk EG0020 affected125 at risk EG003
Blood creatinine increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Blood glucose increased	Investigations	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Haemoglobin decreased	Investigations	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Weight decreased	Investigations	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0011 affected51 at risk EG0020 affected125 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0022 affected125 at risk EG003
Diffuse large B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Hepatocellular carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Oesophageal squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0022 affected125 at risk EG003
Squamous cell carcinoma of lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0022 affected125 at risk EG003
Cerebral ischaemia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Dysarthria	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Haemorrhage intracranial	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Depression	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Suicide attempt	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Acute prerenal failure	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Renal failure chronic	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0011 affected51 at risk EG0020 affected125 at risk EG003
Renal impairment	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Renal injury	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Gynaecomastia	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Ovarian cyst	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Pulmonary granuloma	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0010 affected51 at risk EG0021 affected125 at risk EG003
Haematoma	Vascular disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0010 affected51 at risk EG0020 affected125 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0004 affected106 at risk EG0013 affected51 at risk EG0023 affected125 at risk EG0034 affected106 at risk EG0043 affected51 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0011 affected51 at risk EG0021 affected125 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0002 affected106 at risk EG0012 affected51 at risk EG0028 affected125 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00010 affected106 at risk EG0013 affected51 at risk EG0024 affected125 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected106 at risk EG0011 affected51 at risk EG0029 affected125 at risk EG003
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0012 affected51 at risk EG00210 affected125 at risk EG003
Oedema peripheral	General disorders	MedDRA	Systematic Assessment	EG0004 affected106 at risk EG0014 affected51 at risk EG0022 affected125 at risk EG003
Hepatitis C	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0012 affected51 at risk EG0023 affected125 at risk EG003
Influenza	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected106 at risk EG0013 affected51 at risk EG0020 affected125 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0005 affected106 at risk EG0015 affected51 at risk EG0024 affected125 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0004 affected106 at risk EG0012 affected51 at risk EG0024 affected125 at risk EG003
Incisional hernia	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0002 affected106 at risk EG0016 affected51 at risk EG0022 affected125 at risk EG003
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0006 affected106 at risk EG0014 affected51 at risk EG0023 affected125 at risk EG003
Osteoporosis	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected106 at risk EG0013 affected51 at risk EG0021 affected125 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 affected106 at risk EG0013 affected51 at risk EG0020 affected125 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA	Systematic Assessment	EG0001 affected106 at risk EG0011 affected51 at risk EG00210 affected125 at risk EG003
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0008 affected106 at risk EG0012 affected51 at risk EG0025 affected125 at risk EG003

ID	Term
D018942	Macrolides
D007783	Lactones
D009930	Organic Chemicals
D020123	Sirolimus
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists

ID	Title	Description
BG000	Everolimus + Reduced Tacrolimus	Participants were maintained on whole blood trough levels of 3 - 8 ng/mL everolimus and 3 - 5 ng/mL tacrolimus.
BG001	Tacrolimus Elimination	Participants were maintained on a whole blood trough level of 6 - 10 ng/mL everolimus.
BG002	Tacrolimus Control	Participants were maintained on a whole blood trough level of 6 - 10 ng/mL tacrolimus.
BG003	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Reduced TAC, Month 36	Reduced TAC, Month 36	32	106	38	106
EG001	TAC Elimination, Month 36	TAC Elimination, Month 36	16	51	29	51
EG002	TAC Control, Month 36	TAC Control, Month 36	28	125	43	125
EG003	Reduced RAD + TAC, Month 48	Reduced RAD + TAC, Month 48	34	106	43	106
EG004	TAC Elimination, Month 48	TAC Elimination, Month 48	24	51	36	51

ID	Term
D016559	Tacrolimus
D000068338	Everolimus
D000305	Adrenal Cortex Hormones