Study Of The Safety And Efficacy Of Conversion From A CNI... | NCT00369382

ID	Type	Description	Link
B1741006	Other Identifier	Pfizer

Label	Type	Description	Intervention Names
1	Active Comparator	Group 1: Continuation of CNI regimen	Drug: cyclosporine or tacrolimus
2	Experimental	Group 2: (CNI-Free) Conversion to SRL-based regimen	Drug: sirolimus

Name	Type	Description	Arm Group Labels	Other Names
cyclosporine or tacrolimus	Drug	Cyclosporine and tacrolimus are provided by the sites and dosed to achieve a target trough level determined by the investigator; therefore, form, dosage, and frequency are site and patient specific. Duration should be 52 weeks on-therapy.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Calculated Creatinine Clearance (Cockcroft-Gault Equation) at 52 Weeks Post-randomization	Creatinine Clearance (CC) calculated using Cockcroft-Gault equation, adjusted for body surface area. Calculated CC: method to approximate kidney function. It measures rate creatinine (substance formed from metabolism of creatine) is cleared from blood by kidneys. Normal adult creatinine clearance is greater than or equal to (≥) 90 milliliters per minute per 1.73 meters squared (mL/min/1.73m^2). Change from baseline=CC at Week 52 minus CC at baseline where higher scores represented improved renal function; Least squares mean adjusted for baseline calculated creatinine clearance and center.	Baseline and Week 52
Calculated Creatinine Clearance (Cockcroft-Gault Equation) at Baseline	Creatinine clearance at baseline calculated using Cockcroft-Gault equation and adjusted for body surface area. Calculated CC: method to approximate kidney function. It measures rate creatinine (substance formed from metabolism of creatine) is cleared from blood by kidneys. Normal adult creatinine clearance is ≥ 90 mL/min/1.73m^2.	Baseline

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Calculated Creatinine Clearance (Cockcroft-Gault Equation) at 4, 16, 24, 32, and 40 Weeks Post-randomization	Creatinine Clearance (CC) calculated using Cockcroft-Gault equation, adjusted for body surface area. Calculated CC: method to approximate kidney function. It measures rate creatinine (substance formed from metabolism of creatine) is cleared from blood by kidneys. Normal adult creatinine clearance is ≥ 90 mL/min/1.73m^2. Change from baseline=CC at Week X minus CC at baseline where higher scores represented improved renal function; Least squares mean adjusted for baseline calculated creatinine clearance and center.

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pfizer Investigational Site		Tampa	Florida	33606	United States
Pfizer Investigational Site

PubMed Identifier	Type	Citation	Retractions
22776430	Derived	Zuckermann A, Keogh A, Crespo-Leiro MG, Mancini D, Vilchez FG, Almenar L, Brozena S, Eisen H, Tai SS, Kushwaha S. Randomized controlled trial of sirolimus conversion in cardiac transplant recipients with renal insufficiency. Am J Transplant. 2012 Sep;12(9):2487-97. doi: 10.1111/j.1600-6143.2012.04131.x. Epub 2012 Jul 9.

Label	URL
To obtain contact information for a study center near you, click here.	View source

ID	Title	Description
FG000	Cyclosporine or Tacrolimus	Continuation of Calcineurin inhibitor (CNI) regimen; included cyclosporine (CsA) or tacrolimus (TAC) which were dosed to achieve a target trough level determined by investigator; therefore, form, dosage, and frequency were site and patient specific. CsA therapy could have been switched to TAC therapy and vice versa, as warranted by clinical circumstances.

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

Change From Baseline in Calculated Creatinine Clearance (Cockcroft-Gault Equation) at 52 Weeks Post-randomization

Creatinine Clearance (CC) calculated using Cockcroft-Gault equation, adjusted for body surface area. Calculated CC: method to approximate kidney function. It measures rate creatinine (substance formed from metabolism of creatine) is cleared from blood by kidneys. Normal adult creatinine clearance is greater than or equal to (≥) 90 milliliters per minute per 1.73 meters squared (mL/min/1.73m^2). Change from baseline=CC at Week 52 minus CC at baseline where higher scores represented improved renal function; Least squares mean adjusted for baseline calculated creatinine clearance and center.

Intent-to-Treat (ITT) Population: all randomized participants; all available data (on-therapy and off-therapy) included; Last observation carried forward (LOCF) for data missing due to skipped visits or participant withdrawal from study. Number of participants analyzed (N)=those with all measurements required for calculated creatinine clearance.

Posted

Least Squares Mean

Standard Error

mL/min/1.73m^2

Baseline and Week 52

ID	Title	Description
OG000	Cyclosporine or Tacrolimus	Continuation of Calcineurin inhibitor (CNI) regimen; included cyclosporine (CsA) or tacrolimus (TAC) which were dosed to achieve a target trough level determined by investigator; therefore, form, dosage, and frequency were site and patient specific. CsA therapy could have been switched to TAC therapy and vice versa, as warranted by clinical circumstances.
OG001	Sirolimus (SRL)	Conversion from CNI therapy to Sirolimus: Sirolimus initiated with oral tablets administered once daily (1 to 5 milligrams per day) to achieve target trough of 8-15 nanograms per milliliter (ng/mL). Protocol was later amended to allow target troughs of 7-15 ng/mL for duration of study. CNI discontinued within 8 weeks post randomization.

Units	Counts
Participants	OG00059 OG00156

Title

Denominators

Categories

Title	Measurements
	OG000-1.35± 1.18 OG0013.03± 1.29

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Change from baseline to Week 52	ANCOVA	Analysis of covariance (ANCOVA) with baseline creatinine clearance (Cockcroft-Gault) as a covariate and treatment group and center as factors	0.004	two-sided alpha = 0.05					2-Sided							No	Superiority or Other

Primary

Calculated Creatinine Clearance (Cockcroft-Gault Equation) at Baseline

Creatinine clearance at baseline calculated using Cockcroft-Gault equation and adjusted for body surface area. Calculated CC: method to approximate kidney function. It measures rate creatinine (substance formed from metabolism of creatine) is cleared from blood by kidneys. Normal adult creatinine clearance is ≥ 90 mL/min/1.73m^2.

ITT; N=participants with all measurements required for calculated creatinine clearance.

Posted

Mean

Standard Deviation

mL/min/1.73m^2

Baseline

ID	Title	Description
OG000	Cyclosporine or Tacrolimus	Continuation of Calcineurin inhibitor (CNI) regimen; included cyclosporine (CsA) or tacrolimus (TAC) which were dosed to achieve a target trough level determined by investigator; therefore, form, dosage, and frequency were site and patient specific. CsA therapy could have been switched to TAC therapy and vice versa, as warranted by clinical circumstances.
OG001	Sirolimus (SRL)	Conversion from CNI therapy to Sirolimus: Sirolimus initiated with oral tablets administered once daily (1 to 5 milligrams per day) to achieve target trough of 8-15 nanograms per milliliter (ng/mL). Protocol was later amended to allow target troughs of 7-15 ng/mL for duration of study. CNI discontinued within 8 weeks post randomization.

Secondary

Change From Baseline in Calculated Creatinine Clearance (Cockcroft-Gault Equation) at 4, 16, 24, 32, and 40 Weeks Post-randomization

Creatinine Clearance (CC) calculated using Cockcroft-Gault equation, adjusted for body surface area. Calculated CC: method to approximate kidney function. It measures rate creatinine (substance formed from metabolism of creatine) is cleared from blood by kidneys. Normal adult creatinine clearance is ≥ 90 mL/min/1.73m^2. Change from baseline=CC at Week X minus CC at baseline where higher scores represented improved renal function; Least squares mean adjusted for baseline calculated creatinine clearance and center.

ITT; All available data (on-therapy and off-therapy) were included; LOCF for data points missing due to skipped visits or participant withdrawal from study; N=participants with all measurements required for calculated creatinine clearance.

Posted

Least Squares Mean

Standard Error

mL/min/1.73m^2

Baseline and Weeks 4, 16, 24, 32, and 40

ID	Title	Description
OG000	Cyclosporine or Tacrolimus	Continuation of Calcineurin inhibitor (CNI) regimen; included cyclosporine (CsA) or tacrolimus (TAC) which were dosed to achieve a target trough level determined by investigator; therefore, form, dosage, and frequency were site and patient specific. CsA therapy could have been switched to TAC therapy and vice versa, as warranted by clinical circumstances.
OG001	Sirolimus (SRL)	Conversion from CNI therapy to Sirolimus: Sirolimus initiated with oral tablets administered once daily (1 to 5 milligrams per day) to achieve target trough of 8-15 nanograms per milliliter (ng/mL). Protocol was later amended to allow target troughs of 7-15 ng/mL for duration of study. CNI discontinued within 8 weeks post randomization.

Secondary

Change From Baseline in Calculated Creatinine Clearance (Modification of Diet in Renal Disease [MDRD] Equation) at 4, 16, 24, 32, 40 and 52 Weeks Post-randomization

Creatinine clearance calculated using MDRD equation. Normal adult creatinine clearance is ≥ 90 mL/min/1.73m^2. Change from baseline=CC at Week X minus CC at baseline where higher scores represented improved renal function. Least squares mean adjusted for baseline calculated creatinine clearance (MDRD) and center.

ITT; All available data (on-therapy and off-therapy) were included; LOCF for data points missing due to skipped visits or participant withdrawal from study.

Posted

Least Squares Mean

Standard Error

mL/min/1.73m^2

Baseline and Weeks 4, 16, 24, 32, 40 and 52

ID	Title	Description
OG000	Cyclosporine or Tacrolimus	Continuation of Calcineurin inhibitor (CNI) regimen; included cyclosporine (CsA) or tacrolimus (TAC) which were dosed to achieve a target trough level determined by investigator; therefore, form, dosage, and frequency were site and patient specific. CsA therapy could have been switched to TAC therapy and vice versa, as warranted by clinical circumstances.
OG001	Sirolimus (SRL)	Conversion from CNI therapy to Sirolimus: Sirolimus initiated with oral tablets administered once daily (1 to 5 milligrams per day) to achieve target trough of 8-15 nanograms per milliliter (ng/mL). Protocol was later amended to allow target troughs of 7-15 ng/mL for duration of study. CNI discontinued within 8 weeks post randomization.

Secondary

Calculated Creatinine Clearance (Modification of Diet in Renal Disease [MDRD] Equation) at Baseline

Creatinine clearance calculated using MDRD equation. Calculated CC: method to approximate kidney function. It measures rate creatinine (substance formed from metabolism of creatine) is cleared from blood by kidneys. Normal adult creatinine clearance is ≥ 90 mL/min/1.73m^2.

ITT.

Posted

Mean

Standard Deviation

mL/min/1.73m^2

Baseline

ID	Title	Description
OG000	Cyclosporine or Tacrolimus	Continuation of Calcineurin inhibitor (CNI) regimen; included cyclosporine (CsA) or tacrolimus (TAC) which were dosed to achieve a target trough level determined by investigator; therefore, form, dosage, and frequency were site and patient specific. CsA therapy could have been switched to TAC therapy and vice versa, as warranted by clinical circumstances.
OG001	Sirolimus (SRL)	Conversion from CNI therapy to Sirolimus: Sirolimus initiated with oral tablets administered once daily (1 to 5 milligrams per day) to achieve target trough of 8-15 nanograms per milliliter (ng/mL). Protocol was later amended to allow target troughs of 7-15 ng/mL for duration of study. CNI discontinued within 8 weeks post randomization.

Secondary

Change From Baseline in Serum Creatinine Level at 4, 16, 24, 32, 40, and 52 Weeks Post-randomization

Serum creatinine is an indicator of kidney function. Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine, and muscle tissue. It is removed from the blood by the kidneys and excreted in urine. Normal adult blood levels of creatinine=45 to 90 micromoles per liter (mcmol/L) for females, 60 to 110 mcmol/L for males, however normal values are age-dependent. Change from baseline=creatinine level at Week x minus baseline level where higher scores represented decreased kidney function. Least squares mean adjusted for treatment group and center.

ITT, All available data (on-therapy and off-therapy) were included; LOCF for data points missing due to skipped visits or participant withdrawal from study.

Posted

Least Squares Mean

Standard Error

mcmol/L

Baseline and Weeks 4, 16, 24, 32, 40, and 52

ID	Title	Description
OG000	Cyclosporine or Tacrolimus	Continuation of Calcineurin inhibitor (CNI) regimen; included cyclosporine (CsA) or tacrolimus (TAC) which were dosed to achieve a target trough level determined by investigator; therefore, form, dosage, and frequency were site and patient specific. CsA therapy could have been switched to TAC therapy and vice versa, as warranted by clinical circumstances.
OG001	Sirolimus (SRL)	Conversion from CNI therapy to Sirolimus: Sirolimus initiated with oral tablets administered once daily (1 to 5 milligrams per day) to achieve target trough of 8-15 nanograms per milliliter (ng/mL). Protocol was later amended to allow target troughs of 7-15 ng/mL for duration of study. CNI discontinued within 8 weeks post randomization.

Secondary

Serum Creatinine Level at Baseline

ITT.

Posted

Mean

Standard Deviation

mcmol/L

Baseline

ID	Title	Description
OG000	Cyclosporine or Tacrolimus	Continuation of Calcineurin inhibitor (CNI) regimen; included cyclosporine (CsA) or tacrolimus (TAC) which were dosed to achieve a target trough level determined by investigator; therefore, form, dosage, and frequency were site and patient specific. CsA therapy could have been switched to TAC therapy and vice versa, as warranted by clinical circumstances.
OG001	Sirolimus (SRL)	Conversion from CNI therapy to Sirolimus: Sirolimus initiated with oral tablets administered once daily (1 to 5 milligrams per day) to achieve target trough of 8-15 nanograms per milliliter (ng/mL). Protocol was later amended to allow target troughs of 7-15 ng/mL for duration of study. CNI discontinued within 8 weeks post randomization.

Units	Counts

Secondary

Annual Change in Calculated Creatinine Clearance (Cockcroft-Gault Equation)

The change in creatinine clearance over time assessed using the random coefficient slope of the regression line with creatinine clearance as the dependent variable and study day as the independent variable. Time points calculated as study days, relative to time of randomization of study medication. Observed data multiplied by a scale factor of 365 to express an annual change.

ITT; N=participants with all measurements required for calculated creatinine clearance. All observed data up to the point of discontinuation of the study were used.

Posted

Number

95% Confidence Interval

mL/min/1.73m^2

Baseline to discontinuation (up to Week 52)

ID	Title	Description
OG000	Cyclosporine or Tacrolimus	Continuation of Calcineurin inhibitor (CNI) regimen; included cyclosporine (CsA) or tacrolimus (TAC) which were dosed to achieve a target trough level determined by investigator; therefore, form, dosage, and frequency were site and patient specific. CsA therapy could have been switched to TAC therapy and vice versa, as warranted by clinical circumstances.
OG001	Sirolimus (SRL)	Conversion from CNI therapy to Sirolimus: Sirolimus initiated with oral tablets administered once daily (1 to 5 milligrams per day) to achieve target trough of 8-15 nanograms per milliliter (ng/mL). Protocol was later amended to allow target troughs of 7-15 ng/mL for duration of study. CNI discontinued within 8 weeks post randomization.

Secondary

Overall Survival (OS)

Survival time from the start of study treatment to date of death due to any cause, censored at the last visit if no death. Death was determined from the Death report. The distribution of time to death was to be estimated using Kaplan-Meier method and compared between treatment groups with a proportional hazard model. The number and percent of survival at 6 and 12 months were to be reported.

Safety population: all randomized participants who received at least 1 dose of study medication; not analyzed by Kaplan-Meier because number of events limited to 2 deaths in the sirolimus group.

Posted

Number

Weeks

Baseline until death (up to Week 56)

ID	Title	Description
OG000	Cyclosporine or Tacrolimus	Continuation of Calcineurin inhibitor (CNI) regimen; included cyclosporine (CsA) or tacrolimus (TAC) which were dosed to achieve a target trough level determined by investigator; therefore, form, dosage, and frequency were site and patient specific. CsA therapy could have been switched to TAC therapy and vice versa, as warranted by clinical circumstances.
OG001	Sirolimus (SRL)	Conversion from CNI therapy to Sirolimus: Sirolimus initiated with oral tablets administered once daily (1 to 5 milligrams per day) to achieve target trough of 8-15 nanograms per milliliter (ng/mL). Protocol was later amended to allow target troughs of 7-15 ng/mL for duration of study. CNI discontinued within 8 weeks post randomization.

Secondary

Number of Participants With Acute Rejection

Based on International Society for Heart and Lung Transplantation [ISHLT] 1990 criteria: rejections Grade 3A or higher, rejection accompanied by hemodynamic compromise or requiring treatment. Grade 3A or higher included: multifocal aggressive infiltrates and/or myocyte damage, diffuse inflammatory process with necrosis, diffuse aggressive polymorphus with necrosis, increased infiltrates, and changes in edema, hemorrhage, or vasculitis. Biopsies performed for clinically suspected rejection (for cause), site's standard of care (site protocol biopsy), or protocol mandated.

Safety population; n=number of participants analyzed for the specified type of biopsy.

Posted

Number

Participants

Baseline to Week 52

ID	Title	Description
OG000	Cyclosporine or Tacrolimus	Continuation of Calcineurin inhibitor (CNI) regimen; included cyclosporine (CsA) or tacrolimus (TAC) which were dosed to achieve a target trough level determined by investigator; therefore, form, dosage, and frequency were site and patient specific. CsA therapy could have been switched to TAC therapy and vice versa, as warranted by clinical circumstances.
OG001	Sirolimus (SRL)	Conversion from CNI therapy to Sirolimus: Sirolimus initiated with oral tablets administered once daily (1 to 5 milligrams per day) to achieve target trough of 8-15 nanograms per milliliter (ng/mL). Protocol was later amended to allow target troughs of 7-15 ng/mL for duration of study. CNI discontinued within 8 weeks post randomization.

Secondary

Number of Participants With Biopsy-confirmed Acute Rejection by Severity

Severity of acute rejection summarized using revised 2005 ISHLT criteria. Grade 0R: no rejection, Grade 1R: Focal (perivascular or interstitial) infiltrate without necrosis, diffuse but sparse infiltrate without necrosis, or one focus only with aggressive infiltration and/or focal myocyte damage, Grade 2R:Multifocal aggressive infiltrates and/or myocyte damage, and Grade 3R:Diffuse inflammatory process with necrosis, or diffuse aggressive polymorphous with necrosis, increased infiltrate, changes in edema, hemorrhage and vasculitis.

Safety population

Posted

Number

Participants

Baseline to Week 52

ID	Title	Description
OG000	Cyclosporine or Tacrolimus	Continuation of Calcineurin inhibitor (CNI) regimen; included cyclosporine (CsA) or tacrolimus (TAC) which were dosed to achieve a target trough level determined by investigator; therefore, form, dosage, and frequency were site and patient specific. CsA therapy could have been switched to TAC therapy and vice versa, as warranted by clinical circumstances.
OG001	Sirolimus (SRL)	Conversion from CNI therapy to Sirolimus: Sirolimus initiated with oral tablets administered once daily (1 to 5 milligrams per day) to achieve target trough of 8-15 nanograms per milliliter (ng/mL). Protocol was later amended to allow target troughs of 7-15 ng/mL for duration of study. CNI discontinued within 8 weeks post randomization.

Secondary

Time to First Acute Rejection

Time from baseline to first biopsy-confirmed acute rejection defined as any of the following (based on ISHLT 1990 criteria): all rejections Grade 3A or higher, any rejection accompanied by hemodynamic compromise, or any rejection requiring treatment. ISHLT Grade 3A or higher included: Multifocal aggressive infiltrates and/or myocyte damage, diffuse inflammatory process with necrosis, diffuse aggressive polymorphus with necrosis, increased infiltrates, and changes in edema, hemorrhage, or vasculitis.

Safety population; not analyzed because actual start date of rejection was unknown for those diagnosed by site protocol (SOC) biopsy and protocol-required biopsy.

Posted

Number

Weeks

Baseline to Week 52

ID	Title	Description
OG000	Cyclosporine or Tacrolimus	Continuation of Calcineurin inhibitor (CNI) regimen; included cyclosporine (CsA) or tacrolimus (TAC) which were dosed to achieve a target trough level determined by investigator; therefore, form, dosage, and frequency were site and patient specific. CsA therapy could have been switched to TAC therapy and vice versa, as warranted by clinical circumstances.
OG001	Sirolimus (SRL)	Conversion from CNI therapy to Sirolimus: Sirolimus initiated with oral tablets administered once daily (1 to 5 milligrams per day) to achieve target trough of 8-15 nanograms per milliliter (ng/mL). Protocol was later amended to allow target troughs of 7-15 ng/mL for duration of study. CNI discontinued within 8 weeks post randomization.

Secondary

Number of Participants Requiring Antibody Use in Treatment of Acute Rejection

Number of participants requiring antilymphocyte antibody therapy with suspected or biopsy-proven, steroid-resistant, acute rejection with or without hemodynamic compromise. Acute rejection based on ISHLT 1990 criteria: all rejections Grade 3A or higher, any rejection accompanied by hemodynamic compromise, or any rejection requiring treatment. ISHLT Grade 3A or higher included: Multifocal aggressive infiltrates and/or myocyte damage, diffuse inflammatory process with necrosis, diffuse aggressive polymorphus with necrosis, increased infiltrates, and changes in edema, hemorrhage, or vasculitis.

Safety population; N=participants who had biopsy-confirmed acute rejection.

Posted

Number

Participants

Baseline to Week 52

ID	Title	Description
OG000	Cyclosporine or Tacrolimus	Continuation of Calcineurin inhibitor (CNI) regimen; included cyclosporine (CsA) or tacrolimus (TAC) which were dosed to achieve a target trough level determined by investigator; therefore, form, dosage, and frequency were site and patient specific. CsA therapy could have been switched to TAC therapy and vice versa, as warranted by clinical circumstances.
OG001	Sirolimus (SRL)	Conversion from CNI therapy to Sirolimus: Sirolimus initiated with oral tablets administered once daily (1 to 5 milligrams per day) to achieve target trough of 8-15 nanograms per milliliter (ng/mL). Protocol was later amended to allow target troughs of 7-15 ng/mL for duration of study. CNI discontinued within 8 weeks post randomization.

Secondary

Number of Participants in Sirolimus Treatment Group Requiring Conversion Back to CNI Therapy

Safety population.

Posted

Number

Participants

Baseline up to Week 52

ID	Title	Description
OG000	Sirolimus (SRL)	Conversion from CNI therapy to Sirolimus: Sirolimus initiated with oral tablets administered once daily (1 to 5 milligrams per day) to achieve target trough of 8-15 nanograms per milliliter (ng/mL). Protocol was later amended to allow target troughs of 7-15 ng/mL for duration of study. CNI discontinued within 8 weeks post randomization.

Units	Counts
Participants	OG00057

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Abdominal pain	General disorders	COSTART(unspecified)	Systematic Assessment	Body as a Whole	EG0001 affected57 at risk EG0011 affected57 at risk
Asthenia	General disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0011 affected57 at risk
Fever	General disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0011 affected57 at risk
Lab test abnormal	General disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0010 affected57 at risk
Sudden death	General disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0011 affected57 at risk
Transplant rejection	General disorders	COSTART(unspecified)	Systematic Assessment	Multiple reasons for cardiac biopsies. Refer to outcome measure 10.	EG0001 affected57 at risk EG00113 affected57 at risk
Angina pectoris	Cardiac disorders	COSTART(unspecified)	Systematic Assessment	Cardiovascular System	EG0001 affected57 at risk EG0010 affected57 at risk
Arrhythmia	Cardiac disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0011 affected57 at risk
Cerebral ischemia	Cardiac disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0011 affected57 at risk
Endocarditis	Cardiac disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0011 affected57 at risk
Hypertension	Cardiac disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0011 affected57 at risk
Hypotension	Cardiac disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0011 affected57 at risk
Pericardial effusion	Cardiac disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0011 affected57 at risk
Sick sinus syndrome	Cardiac disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0011 affected57 at risk
Syncope	Cardiac disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0010 affected57 at risk
Biliary pain	Gastrointestinal disorders	COSTART(unspecified)	Systematic Assessment	Digestive System	EG0000 affected57 at risk EG0011 affected57 at risk
Cholelithiasis	Gastrointestinal disorders	COSTART(unspecified)	Systematic Assessment		EG0002 affected57 at risk EG0010 affected57 at risk
Constipation	Gastrointestinal disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0010 affected57 at risk
Diarrhea	Gastrointestinal disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0011 affected57 at risk
Gastroenteritis	Gastrointestinal disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0011 affected57 at risk
Gastrointestinal carcinoma	Gastrointestinal disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0011 affected57 at risk
Gastrointestinal disorder	Gastrointestinal disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0011 affected57 at risk
Liver function tests abnormal	Gastrointestinal disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0011 affected57 at risk
Rectal hemorrhage	Gastrointestinal disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0011 affected57 at risk
Anemia	Blood and lymphatic system disorders	COSTART(unspecified)	Systematic Assessment	Hemic and lymphatic system	EG0000 affected57 at risk EG0011 affected57 at risk
Arthrosis	Musculoskeletal and connective tissue disorders	COSTART(unspecified)	Systematic Assessment	Musculoskeletal system	EG0001 affected57 at risk EG0010 affected57 at risk
Myalgia	Musculoskeletal and connective tissue disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0013 affected57 at risk
Confusion	Nervous system disorders	COSTART(unspecified)	Systematic Assessment	Nervous system	EG0000 affected57 at risk EG0011 affected57 at risk
Bronchitis	Respiratory, thoracic and mediastinal disorders	COSTART(unspecified)	Systematic Assessment	Respiratory system	EG0000 affected57 at risk EG0011 affected57 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0011 affected57 at risk
Pharyngitis	Respiratory, thoracic and mediastinal disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0011 affected57 at risk
Pneumonia	Respiratory, thoracic and mediastinal disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0014 affected57 at risk
Upper respiratory infection	Respiratory, thoracic and mediastinal disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0012 affected57 at risk
Herpes zoster	Skin and subcutaneous tissue disorders	COSTART(unspecified)	Systematic Assessment	Skin and appendages	EG0001 affected57 at risk EG0010 affected57 at risk
Skin carcinoma	Skin and subcutaneous tissue disorders	COSTART(unspecified)	Systematic Assessment		EG0003 affected57 at risk EG0012 affected57 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Abdominal pain	General disorders	COSTART(unspecified)	Systematic Assessment	Body as a Whole	EG0003 affected57 at risk EG0017 affected57 at risk
Accidental injury	General disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0014 affected57 at risk
Asthenia	General disorders	COSTART(unspecified)	Systematic Assessment		EG0005 affected57 at risk EG0015 affected57 at risk
Back pain	General disorders	COSTART(unspecified)	Systematic Assessment		EG0002 affected57 at risk EG0014 affected57 at risk
Chest pain	General disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0013 affected57 at risk
Face edema	General disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0015 affected57 at risk
Fever	General disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0014 affected57 at risk
Generalized edema	General disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0013 affected57 at risk
Headache	General disorders	COSTART(unspecified)	Systematic Assessment		EG0002 affected57 at risk EG0018 affected57 at risk
Pain	General disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0015 affected57 at risk
Transplant rejection	General disorders	COSTART(unspecified)	Systematic Assessment	Multiple reasons for cardiac biopsies. Refer to outcome measure 10.	EG0001 affected57 at risk EG0014 affected57 at risk
Hypertension	Cardiac disorders	COSTART(unspecified)	Systematic Assessment	Cardiovascular system	EG0002 affected57 at risk EG0017 affected57 at risk
Tachycardia sinus	Cardiac disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0013 affected57 at risk
Anorexia	Gastrointestinal disorders	COSTART(unspecified)	Systematic Assessment	Digestive system	EG0000 affected57 at risk EG0013 affected57 at risk
Aphthous stomatitis	Gastrointestinal disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0018 affected57 at risk
Diarrhea	Gastrointestinal disorders	COSTART(unspecified)	Systematic Assessment		EG0006 affected57 at risk EG00115 affected57 at risk
Liver function tests abnormal	Gastrointestinal disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0013 affected57 at risk
Mouth ulceration	Gastrointestinal disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0016 affected57 at risk
Nausea	Gastrointestinal disorders	COSTART(unspecified)	Systematic Assessment		EG0005 affected57 at risk EG0015 affected57 at risk
Stomatitis	Gastrointestinal disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0013 affected57 at risk
Anemia	Blood and lymphatic system disorders	COSTART(unspecified)	Systematic Assessment	Hemic and Lymphatic system	EG0000 affected57 at risk EG0015 affected57 at risk
Ecchymosis	Blood and lymphatic system disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0015 affected57 at risk
Leukopenia	Blood and lymphatic system disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0014 affected57 at risk
Creatinine increased	Metabolism and nutrition disorders	COSTART(unspecified)	Systematic Assessment	Metabolic and Nutritional	EG0003 affected57 at risk EG0010 affected57 at risk
Gout	Metabolism and nutrition disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0014 affected57 at risk
Healing abnormal	Metabolism and nutrition disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0013 affected57 at risk
Hypercholesteremia	Metabolism and nutrition disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0016 affected57 at risk
Hyperlipemia	Metabolism and nutrition disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0016 affected57 at risk
Peripheral edema	Metabolism and nutrition disorders	COSTART(unspecified)	Systematic Assessment		EG0009 affected57 at risk EG00118 affected57 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	COSTART(unspecified)	Systematic Assessment	Musculoskeletal system	EG0002 affected57 at risk EG0016 affected57 at risk
Myalgia	Musculoskeletal and connective tissue disorders	COSTART(unspecified)	Systematic Assessment		EG0005 affected57 at risk EG0014 affected57 at risk
Anxiety	Nervous system disorders	COSTART(unspecified)	Systematic Assessment	Nervous system	EG0000 affected57 at risk EG0013 affected57 at risk
Depression	Nervous system disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0013 affected57 at risk
Dizziness	Nervous system disorders	COSTART(unspecified)	Systematic Assessment		EG0004 affected57 at risk EG0015 affected57 at risk
Insomnia	Nervous system disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0014 affected57 at risk
Somnolence	Nervous system disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0015 affected57 at risk
Cough increased	Respiratory, thoracic and mediastinal disorders	COSTART(unspecified)	Systematic Assessment	Respiratory system	EG0006 affected57 at risk EG0015 affected57 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	COSTART(unspecified)	Systematic Assessment		EG0005 affected57 at risk EG0016 affected57 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0014 affected57 at risk
Pharyngitis	Respiratory, thoracic and mediastinal disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0013 affected57 at risk
Acne	Skin and subcutaneous tissue disorders	COSTART(unspecified)	Systematic Assessment	Skin and Appendages	EG0000 affected57 at risk EG0018 affected57 at risk
Dry skin	Skin and subcutaneous tissue disorders	COSTART(unspecified)	Systematic Assessment		EG0000 affected57 at risk EG0013 affected57 at risk
Rash	Skin and subcutaneous tissue disorders	COSTART(unspecified)	Systematic Assessment		EG0002 affected57 at risk EG00116 affected57 at risk
Sweating	Skin and subcutaneous tissue disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected57 at risk EG0014 affected57 at risk
Eye pruritus	Eye disorders	COSTART(unspecified)	Systematic Assessment	Special senses	EG0000 affected57 at risk EG0013 affected57 at risk
Uterine fibroids enlarged	Renal and urinary disorders	COSTART(unspecified)	Systematic Assessment	Urogenital system	EG0001 affected5 at risk EG0010 affected12 at risk
Uterine hemorrhage	Renal and urinary disorders	COSTART(unspecified)	Systematic Assessment		EG0001 affected5 at risk EG0010 affected12 at risk
Infection	General disorders	COSTART(unspecified)	Systematic Assessment	Body as a whole	EG0000 affected57 at risk EG0015 affected57 at risk
Pharyngitis	Respiratory, thoracic and mediastinal disorders	COSTART(unspecified)	Systematic Assessment	Due to infection, Respiratory system	EG0000 affected57 at risk EG0013 affected57 at risk
Upper respiratory infection	Respiratory, thoracic and mediastinal disorders	COSTART(unspecified)	Systematic Assessment		EG00011 affected57 at risk EG00110 affected57 at risk
Herpes simplex	Skin and subcutaneous tissue disorders	COSTART(unspecified)	Systematic Assessment	Skin and Appendages	EG0000 affected57 at risk EG0014 affected57 at risk
Herpes zoster	Skin and subcutaneous tissue disorders	COSTART(unspecified)	Systematic Assessment		EG0004 affected57 at risk EG0015 affected57 at risk
Skin carcinoma	Skin and subcutaneous tissue disorders	COSTART(unspecified)	Systematic Assessment	Skin and Appendages	EG0001 affected57 at risk EG0013 affected57 at risk

ID	Term
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases

ID	Term
D010456	Peptides, Cyclic
D047028	Macrocyclic Compounds
D011083	Polycyclic Compounds
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D018942	Macrolides
D007783	Lactones
D009930	Organic Chemicals

ID	Title	Description
BG000	Cyclosporine or Tacrolimus	Continuation of Calcineurin inhibitor (CNI) regimen; included cyclosporine (CsA) or tacrolimus (TAC) which were dosed to achieve a target trough level determined by investigator; therefore, form, dosage, and frequency were site and patient specific. CsA therapy could have been switched to TAC therapy and vice versa, as warranted by clinical circumstances.
BG001	Sirolimus (SRL)	Conversion from CNI therapy to Sirolimus: Sirolimus initiated with oral tablets administered once daily (1 to 5 milligrams per day) to achieve target trough of 8-15 nanograms per milliliter (ng/mL). Protocol was later amended to allow target troughs of 7-15 ng/mL for duration of study. CNI discontinued within 8 weeks post randomization.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cyclosporine or Tacrolimus	Continuation of Calcineurin inhibitor (CNI) regimen; included cyclosporine (CsA) or tacrolimus (TAC) which were dosed to achieve a target trough level determined by investigator; therefore, form, dosage, and frequency were site and patient specific. CsA therapy could have been switched to TAC therapy and vice versa, as warranted by clinical circumstances.			13	57	40	57
EG001	Sirolimus (SRL)	Conversion from CNI therapy to Sirolimus: Sirolimus initiated with oral tablets administered once daily (1 to 5 milligrams per day) to achieve target trough of 8-15 nanograms per milliliter (ng/mL). Protocol was later amended to allow target troughs of 7-15 ng/mL for duration of study. CNI discontinued within 8 weeks post randomization.			30	57	54	57

ID	Term
D016572	Cyclosporine
D016559	Tacrolimus
D003524	Cyclosporins
D020123	Sirolimus