A Study of Treatment With NeoRecormon (Epoetin Beta) in Patients With Chronic Renal Anemia

The cardiovascular event was defined as any of the following: angina pectoris leading to hospitalization for at least 24 hours or prolongation of hospitalization, acute heart failure, fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, sudden death, transient cerebral ischemic attack (TIA), peripheral vascular disease (amputation, necrosis), cardiac arrhythmias leading to hospitalization for at least 24 hours or prolongation of hospitalization. The time to occurrence of a cardiovascular event was determined as the time from randomization until any of the above listed events whichever occurred first. The first event per participant was used for the analysis. Only events confirmed by the Endpoint Committee were considered for analysis.

Time frame: Up to 4 years

Population: The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received.

The duration of hospitalization was the total number of days that a participant was hospitalized due to cardiovascular events. Participants with no hospitalization were excluded from analysis.

Time frame: Up to 4 years

Population: The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received. Data for the participants present at the time of assessment was used for analysis.

LVEF is a marker of left ventricular systolic function and determined by echocardiogram. It is expressed as the ratio of left ventricular stroke volume (LVSV) to left ventricular end-diastolic volume (LVEDV), and is measured as a percentage. FS is used as an estimate of myocardial contractility and determined by echocardiogram and measures as a percentage. The change for LVEF and FS was calculated as Week value minus baseline value.

Time frame: Baseline, Week 12, Week 24, Week 36, and Week 48

Population: The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received. The n represents the number of participants assessed for LVEF and FS at Baseline, Week 12, Week 24, Week 36, and Week 48.

LVMI is determined by echocardiogram. LVMI indexed to body surface area (gram/square meter) estimated by LV cavity dimension and wall thickness at end-diastole. The change was calculated as week value minus baseline value.

Time frame: Baseline, Week 12, Week 24, Week 36, and Week 48

Population: The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received. The n represents the number of participants assessed for LVMI at Baseline, Week 12, Week 24, Week 36, and Week 48.

Left Ventricular Volume is the estimated of left ventricular end-diastolic volume (LVEDv) and left ventricular end-systolic volume (LVESV) determined by Echocardiogram. The change was calculated as week value minus baseline value.

Time frame: Baseline, Week 12, Week 24, Week 36, and Week 48

Population: The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received. The n represents the number of participants assessed for LV Volume at Baseline, Week 12, Week 24, Week 36 and Week 48.

The Quality of life was assessed on the basis of a change from baseline in the scores of each of the eight health scales in the SF-36 questionnaire. The SF-36 is a standardized survey evaluating 8 domains (consisting of 2 components; physical and mental) of functional health and well-being: physical and social functioning, physical and emotional role (role-physical, role-emotional) limitations, bodily pain, general health (GH), vitality, mental health. The score for a section is an average of the individual question scores, which are scaled from 0 (worst level of functioning) to 100 (100=best level of functioning). The least squares mean (LSM) change from baseline was determined by Analysis of covariance (ANCOVA) model and presented for each of the eight health scale.

Time frame: Baseline, Year 1, and Year 2

Population: The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received.

The body surface area (BSA) was determined by Echocardiogram. Absolute mean values of Echocardiography (ECHO) Parameter: Body surface area (BSA) at Baseline, Year 1, Year 2, Year 3 and Year 4 were calculated and presented.

Time frame: Baseline, Year 1, Year 2, Year 3, and Year 4.

Population: The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received. The n represents the number of participants assessed for Body surface area through echocardiogram at Baseline, Year 1, Year 2, Year 3 and Year 4.

Mean values of Echocardiography (ECHO) Parameters: Left Ventricular End Diastolic Diameter (LVEDD), Left Ventricular Posterior Wall Thickness (LVPWT), IV Septal Wall Thickness (IVSWT), LV End Systolic Diameter (LVESD), LV Relative wall thickness (LVRWT) at Baseline, Year 1, Year 2, Year 3 and Year 4 were presented.

Time frame: Baseline, Year 1, Year 2, Year 3, and Year 4

Population: The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received. The n represents the number of participants assessed for each echocardiography parameter at Baseline, Year 1, Year 2, Year 3 and Year 4.

Time to death due to all causes is the time determined between randomization and death due to all causes.

Time frame: Up to 4 years

Population: The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received.

Time to death due to cardiovascular events is the time determined between randomization and death due to cardiovascular events.

Time frame: Up to 4 years

Population: The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received.

Time to first cardiovascular intervention is the time between randomization and first intervention determined for all cardiovascular interventions after randomization. Cardiovascular interventions considered were: angioplasty with or without stents/atherectomy, coronary artery bypass surgery, cardioverter defibrillator (CD) cardioversion/defibrillation, temporary pacemaker, permanent pacemaker and implantable cardioverter defibrillator (ICD) implantation.

Time frame: Up to 4 years

Population: The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received.

Time to first hospitalization due to cardiovascular events is defined as the time determined between randomization and first hospitalization due to cardiovascular events.

Time frame: Up to 4 years

Population: The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received.

The NYHA functional classification assesses the severity of symptoms of chronic heart failure and is comprised of four classes. Class I is defined as no limitation of physical activity, Class II is defined as slight limitation of physical activity, Class III is defined as marked limitation of physical activity, and Class IV is defined as unable to carry on any physical activity without discomfort. Shifts of participants from CL 0, CL I, CL II, CL III, CL IV at Baseline (Day 1) to CL 0, CL I, CL II, CL III, CL IV during the study period was determined and presented.

Time frame: Up to 4 years

Population: The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received. The n represents the number of participants assessed for shifts in NYHA class from baseline.

Anti-hypertensive is defined as class of drugs that are used to treat hypertension. Numbers (No.) of participants treated with at least one hypertensive medication/Treatment (Tt) according to class of drugs were reported.

Time frame: Up to 4 years

Population: The safety analysis population included all participants who were randomized and who had received a safety follow-up whether or not they had received epoetin beta treatment.

Number of participants who died due to all causes are presented in table below.

Time frame: Up to 4 years

Population: The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received.

The cardiovascular event was defined as any of the following: angina pectoris leading to hospitalization for at least 24 hours or prolongation of hospitalization, acute heart failure, fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, sudden death, transient cerebral ischemic attack (TIA), peripheral vascular disease (amputation, necrosis), cardiac arrhythmias leading to hospitalization for at least 24 hours or prolongation of hospitalization.

Time frame: Up to 4 years

Population: The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received.

Marked abnormality of laboratory parameters is defined as the value which is outside the defined reference range of that respective parameter. Values above and below the given reference range were determined as High or Low range values of the laboratory parameter. Roche's standard reference ranges for laboratory test parameters were used for the analysis. The laboratory parameters with marked abnormality are platelets (reference range is 150-350 10\^9 cells/liter \[L\]), creatinine (reference range is 0-133 micromole per liter), albumin (reference range is 35.0-55 g/L), phosphate (reference range is 0.84-1.45 millimole per liter \[mmol /L\]) and potassium (reference range is 3.4-4.8 mmol /L).

Time frame: Baseline, every 3 months up to 4 years

Population: The safety analysis population included all participants who were randomized and who had received a safety follow-up whether or not they had received epoetin beta treatment. The ''n represents the number of participants assessed for each laboratory parameter.

Cardiovascular intervention was defined by a clinical review of all concomitant treatments. The cardiovascular interventions considered were: angioplasty with or without stents/atherectomy, coronary artery bypass surgery, cardioverter defibrillator (CD) cardioversion/defibrillation, temporary pacemaker, permanent pacemaker and implantable cardioverter defibrillator (ICD) implantation. The total number of cardiovascular intervention was determined and presented by each cohort.

Time frame: Up to 4 years

Population: The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received.