Trial Outcomes & Findings for A Study of Treatment With NeoRecormon (Epoetin Beta) in Patients With Chronic Renal Anemia (NCT NCT00321919)

NCT ID: NCT00321919

Last Updated: 2016-06-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

605 participants

Primary outcome timeframe

Up to 4 years

Results posted on

2016-06-29

Participant Flow

This study was conducted from 26 July 2000 to 13 December 2004 at 94 centers in 21 countries.

Of the 605 participants, 603 started the study; 2 were withdrawn from the study due to non-compliance with good clinical practice and were excluded from the analysis.

Participant milestones

Participant milestones
Measure	Early Epoetin Beta Therapy Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hemoglobin (Hb) level of 13-15 gram/decilitre (g/dL) with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL has occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Overall Study STARTED	301	302
Overall Study COMPLETED	226	250
Overall Study NOT COMPLETED	75	52

Reasons for withdrawal

Reasons for withdrawal
Measure	Early Epoetin Beta Therapy Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hemoglobin (Hb) level of 13-15 gram/decilitre (g/dL) with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL has occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Overall Study Adverse Event	17	10
Overall Study Death	21	17
Overall Study Insufficient Therapeutic Response	1	0
Overall Study Violation of Selection Criteria at Entry	1	1
Overall Study Refused Treatment	23	14
Overall Study Other Protocol Violation	2	3
Overall Study Failure to Return	3	1
Overall Study Other withdrawal reason	7	6

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Early Epoetin Beta Therapy n=301 Participants Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=302 Participants Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.	Total n=603 Participants Total of all reporting groups
Age, Continuous	59.3 years STANDARD_DEVIATION 14.57 • n=5 Participants	58.8 years STANDARD_DEVIATION 13.73 • n=7 Participants	59.0 years STANDARD_DEVIATION 14.14 • n=5 Participants
Sex: Female, Male Female	130 Participants n=5 Participants	148 Participants n=7 Participants	278 Participants n=5 Participants
Sex: Female, Male Male	171 Participants n=5 Participants	154 Participants n=7 Participants	325 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 4 years

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

Outcome measures

Outcome measures
Measure	Early Epoetin Beta Therapy n=301 Participants Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=302 Participants Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Median Time to First Cardiovascular Event	NA days Data was not available due to insufficient number of participants with cardiovascular events.	NA days Data was not available due to insufficient number of participants with cardiovascular events.

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Early Epoetin Beta Therapy n=301 Participants Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=302 Participants Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Median Time to Death Due to Cardiovascular Events	NA days Data was not available due to insufficient number of deaths due to cardiovascular events.	NA days Data was not available due to insufficient number of deaths due to cardiovascular events.

SECONDARY outcome

Timeframe: Up to 4 years

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

Outcome measures

Outcome measures
Measure	Early Epoetin Beta Therapy n=301 Participants Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=302 Participants Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Number of Participants Who Died Due to Cardiovascular Events Total Cardiovascular Death Events	8 participants	6 participants
Number of Participants Who Died Due to Cardiovascular Events Cardiac Failure	1 participants	2 participants
Number of Participants Who Died Due to Cardiovascular Events Cardiac Failure Acute	1 participants	2 participants
Number of Participants Who Died Due to Cardiovascular Events Acute Myocardial Infarction	1 participants	1 participants
Number of Participants Who Died Due to Cardiovascular Events Angina Pectoris	1 participants	0 participants
Number of Participants Who Died Due to Cardiovascular Events Arrhythmia	1 participants	0 participants
Number of Participants Who Died Due to Cardiovascular Events Cardiac Arrest	1 participants	0 participants
Number of Participants Who Died Due to Cardiovascular Events Cardio-Respiratory Arrest	1 participants	0 participants
Number of Participants Who Died Due to Cardiovascular Events Cardiopulmonary Failure	1 participants	0 participants
Number of Participants Who Died Due to Cardiovascular Events Myocardial Infarction	0 participants	1 participants

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Early Epoetin Beta Therapy n=301 Participants Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=302 Participants Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Median Time to Death Due to All Causes	NA days Data was not available due to insufficient number of deaths due to all causes.	NA days Data was not available due to insufficient number of deaths due to all causes.

SECONDARY outcome

Timeframe: Up to 4 years

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

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

Outcome measures

Outcome measures
Measure	Early Epoetin Beta Therapy n=301 Participants Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=302 Participants Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Number of Participants Who Died Due to All Causes Metastases To Lung	1 participants	0 participants
Number of Participants Who Died Due to All Causes Total Death Events for All-cause	31 participants	21 participants
Number of Participants Who Died Due to All Causes Sudden Death	4 participants	2 participants
Number of Participants Who Died Due to All Causes Cerebrovascular Accident	2 participants	2 participants
Number of Participants Who Died Due to All Causes Cardiac Failure	1 participants	2 participants
Number of Participants Who Died Due to All Causes Cardiac Failure Acute	1 participants	2 participants
Number of Participants Who Died Due to All Causes Sepsis	1 participants	2 participants
Number of Participants Who Died Due to All Causes Acute Myocardial Infarction	1 participants	1 participants
Number of Participants Who Died Due to All Causes Bronchopneumonia	1 participants	1 participants
Number of Participants Who Died Due to All Causes Respiratory Failure	1 participants	1 participants
Number of Participants Who Died Due to All Causes Septic Shock	2 participants	0 participants
Number of Participants Who Died Due to All Causes Acute Heart Failure	1 participants	0 participants
Number of Participants Who Died Due to All Causes Acute Respiratory Failure	0 participants	1 participants
Number of Participants Who Died Due to All Causes Angina Pectoris	1 participants	0 participants
Number of Participants Who Died Due to All Causes Arrhythmia	1 participants	0 participants
Number of Participants Who Died Due to All Causes Cardiac Arrest	1 participants	0 participants
Number of Participants Who Died Due to All Causes Cardio-Respiratory Arrest	1 participants	0 participants
Number of Participants Who Died Due to All Causes Cardiopulmonary Failure	1 participants	0 participants
Number of Participants Who Died Due to All Causes Cerebral Infarction	1 participants	0 participants
Number of Participants Who Died Due to All Causes Clostridial Infection	1 participants	0 participants
Number of Participants Who Died Due to All Causes Colon Cancer Metastatic	0 participants	1 participants
Number of Participants Who Died Due to All Causes Embolic Stroke	1 participants	0 participants
Number of Participants Who Died Due to All Causes Intestinal Infarction	0 participants	1 participants
Number of Participants Who Died Due to All Causes Intestinal Ischaemia	0 participants	1 participants
Number of Participants Who Died Due to All Causes Laryngeal Cancer	1 participants	0 participants
Number of Participants Who Died Due to All Causes Lung Neoplasm Malignant	0 participants	1 participants
Number of Participants Who Died Due to All Causes Metastatic Neoplasm	1 participants	0 participants
Number of Participants Who Died Due to All Causes Myocardial Infarction	0 participants	1 participants
Number of Participants Who Died Due to All Causes Oesophageal Carcinoma	1 participants	0 participants
Number of Participants Who Died Due to All Causes Peripheral Vascular Disorder	1 participants	0 participants
Number of Participants Who Died Due to All Causes Pneumonia	0 participants	1 participants
Number of Participants Who Died Due to All Causes Pulmonary Embolism	0 participants	1 participants
Number of Participants Who Died Due to All Causes Renal Failure	1 participants	0 participants
Number of Participants Who Died Due to All Causes Unevaluable Event	1 participants	0 participants
Number of Participants Who Died Due to All Causes Uraemic Encephalopathy	1 participants	0 participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Early Epoetin Beta Therapy n=167 Participants Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=149 Participants Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL III (BL)to CL II; n = 0, 0	0 participants	0 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL III (BL)to CL III; n = 0, 0	0 participants	0 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL III (BL)to CL IV; n = 0, 0	0 participants	0 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL IV (BL)to CL 0; n = 0, 0	0 participants	0 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL IV (BL)to CL I; n = 0, 0	0 participants	0 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL IV (BL)to CL II; n = 0, 0	0 participants	0 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL IV (BL)to CL III; n = 0, 0	0 participants	0 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL 0 (BL) to CL 0; n = 167, 149	49 participants	42 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL 0 (BL) to CL I; n = 167, 149	7 participants	4 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL 0 (BL) to CL II; n = 167, 149	7 participants	7 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL 0 (BL) to CL III; n = 167, 149	2 participants	1 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL 0 (BL) to CL IV; n = 167, 149	0 participants	0 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL I (BL) to CL 0; n = 37, 43	1 participants	0 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL I (BL) to CL I; n = 37, 43	28 participants	34 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL I (BL) to CL II; n = 37, 43	5 participants	4 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL I (BL) to CL III; n = 37, 43	0 participants	0 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL I (BL) to CL IV; n = 37, 43	0 participants	0 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL II (BL) to CL 0; n = 53, 44	0 participants	0 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL II (BL) to CL I; n = 53, 44	5 participants	1 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL II (BL) to CL II; n = 53, 44	39 participants	37 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL II (BL) to CL III; n = 53, 44	2 participants	4 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL II (BL) to CL IV; n = 53, 44	0 participants	0 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL III (BL) to CL 0; n = 0, 0	0 participants	0 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL III (BL)to CL I; n = 0, 0	0 participants	0 participants
Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) From CL IV (BL)to CL IV; n = 0, 0	0 participants	0 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Early Epoetin Beta Therapy n=301 Participants Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=302 Participants Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Median Time to First Cardiovascular Intervention	NA days Data was not available due to insufficient number of cardiovascular interventions.	NA days Data was not available due to insufficient number of cardiovascular interventions.

SECONDARY outcome

Timeframe: Up to 4 years

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

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.

Outcome measures

Outcome measures
Measure	Early Epoetin Beta Therapy n=301 Participants Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=302 Participants Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Total Number of Cardiovascular Intervention	21 number of cardiovascular intervention	18 number of cardiovascular intervention

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Early Epoetin Beta Therapy n=301 Participants Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=302 Participants Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Median Time to First Hospitalization Due to Cardiovascular Events	NA days Data was not available due to insufficient number of hospitalizations due to cardiovascular events.	NA days Data was not available due to insufficient number of hospitalizations due to cardiovascular events.

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Early Epoetin Beta Therapy n=171 Participants Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=161 Participants Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Duration of Hospitalization for Cardiovascular Events	33.0 days Standard Deviation 42.0	28.2 days Standard Deviation 33.7

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Early Epoetin Beta Therapy n=219 Participants Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=232 Participants Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Mean Change From Baseline in Left Ventricular Mass Index (LVMI) LVMI, Week 12; n = 171, 186	-5.06 gram/square meter Standard Deviation 24.81	-2.87 gram/square meter Standard Deviation 25.16
Mean Change From Baseline in Left Ventricular Mass Index (LVMI) LVMI, Baseline; n = 219, 232	120.32 gram/square meter Standard Deviation 35.03	117.97 gram/square meter Standard Deviation 34.34
Mean Change From Baseline in Left Ventricular Mass Index (LVMI) LVMI, Week 24; n = 136, 146	-6.58 gram/square meter Standard Deviation 26.94	-7.59 gram/square meter Standard Deviation 25.59
Mean Change From Baseline in Left Ventricular Mass Index (LVMI) LVMI, Week 36; n = 74, 81	-1.30 gram/square meter Standard Deviation 36.04	-7.53 gram/square meter Standard Deviation 34.37
Mean Change From Baseline in Left Ventricular Mass Index (LVMI) LVMI, Week 48; n = 2, 11	2.00 gram/square meter Standard Deviation 2.83	-27.27 gram/square meter Standard Deviation 29.47

SECONDARY outcome

Timeframe: Baseline, Week 12, Week 24, Week 36, and Week 48

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.

Outcome measures

Outcome measures
Measure	Early Epoetin Beta Therapy n=219 Participants Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=233 Participants Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Mean Change From Baseline in Left Ventricular Ejection Fraction (LVEF) and Fractional Myocardial Shortening (FS) LVEF, Baseline; n = 219, 233	81.31 percentage Standard Deviation 7.24	81.95 percentage Standard Deviation 7.75
Mean Change From Baseline in Left Ventricular Ejection Fraction (LVEF) and Fractional Myocardial Shortening (FS) LVEF, Week 12; n = 170, 186	-0.08 percentage Standard Deviation 7.32	0.08 percentage Standard Deviation 7.34
Mean Change From Baseline in Left Ventricular Ejection Fraction (LVEF) and Fractional Myocardial Shortening (FS) LVEF, Week 24; n = 135, 147	-0.47 percentage Standard Deviation 6.82	-0.23 percentage Standard Deviation 7.01
Mean Change From Baseline in Left Ventricular Ejection Fraction (LVEF) and Fractional Myocardial Shortening (FS) LVEF, Week 36; n = 74, 81	-0.61 percentage Standard Deviation 8.61	0.24 percentage Standard Deviation 6.75
Mean Change From Baseline in Left Ventricular Ejection Fraction (LVEF) and Fractional Myocardial Shortening (FS) LVEF, Week 48; n = 2,11	-0.46 percentage Standard Deviation 2.92	2.80 percentage Standard Deviation 8.12
Mean Change From Baseline in Left Ventricular Ejection Fraction (LVEF) and Fractional Myocardial Shortening (FS) FS, Baseline; n = 219, 232	43.67 percentage Standard Deviation 7.12	44.67 percentage Standard Deviation 7.86
Mean Change From Baseline in Left Ventricular Ejection Fraction (LVEF) and Fractional Myocardial Shortening (FS) FS, Week 12; n = 196, 212	0.13 percentage Standard Deviation 6.79	0.08 percentage Standard Deviation 7.34
Mean Change From Baseline in Left Ventricular Ejection Fraction (LVEF) and Fractional Myocardial Shortening (FS) FS, Week 24; n = 174, 192	0.11 percentage Standard Deviation 7.10	-0.19 percentage Standard Deviation 7.40
Mean Change From Baseline in Left Ventricular Ejection Fraction (LVEF) and Fractional Myocardial Shortening (FS) FS, Week 36; n = 98, 105	0.05 percentage Standard Deviation 8.16	0.70 percentage Standard Deviation 7.80
Mean Change From Baseline in Left Ventricular Ejection Fraction (LVEF) and Fractional Myocardial Shortening (FS) FS, Week 48; n = 4,12	1.00 percentage Standard Deviation 2.83	3.00 percentage Standard Deviation 8.58

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Early Epoetin Beta Therapy n=218 Participants Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=232 Participants Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Mean Change From Baseline in Left Ventricular Volume (LV Volume ) LV Volume, Baseline; n = 218, 232	67.73 milliliters per meter square Standard Deviation 19.20	65.11 milliliters per meter square Standard Deviation 19.24
Mean Change From Baseline in Left Ventricular Volume (LV Volume ) LV Volume, Week 12; n = 170, 186	-2.83 milliliters per meter square Standard Deviation 15.90	3.15 milliliters per meter square Standard Deviation 15.46
Mean Change From Baseline in Left Ventricular Volume (LV Volume ) LV Volume, Week 24; n = 134, 146	-0.69 milliliters per meter square Standard Deviation 16.44	2.62 milliliters per meter square Standard Deviation 18.56
Mean Change From Baseline in Left Ventricular Volume (LV Volume ) LV Volume, Week 36; n = 72, 80	3.34 milliliters per meter square Standard Deviation 24.29	4.05 milliliters per meter square Standard Deviation 19.08
Mean Change From Baseline in Left Ventricular Volume (LV Volume ) LV Volume, Week 48; n = 2, 11	14.48 milliliters per meter square Standard Deviation 11.52	7.91 milliliters per meter square Standard Deviation 23.37

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Early Epoetin Beta Therapy n=219 Participants Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=233 Participants Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Mean Values of Echocardiography Parameters LVEDD, Baseline, n = 219, 233	5.05 centimeters Standard Deviation 0.67	4.91 centimeters Standard Deviation 0.68
Mean Values of Echocardiography Parameters LVEDD, Year 1, n = 170, 186	4.93 centimeters Standard Deviation 0.62	4.94 centimeters Standard Deviation 0.65
Mean Values of Echocardiography Parameters LVEDD, Year 2, n = 135, 147	4.95 centimeters Standard Deviation 0.63	4.93 centimeters Standard Deviation 0.72
Mean Values of Echocardiography Parameters LVEDD, Year 3, n = 74, 81	5.09 centimeters Standard Deviation 0.71	4.88 centimeters Standard Deviation 0.59
Mean Values of Echocardiography Parameters LVEDD, Year 4, n = 2,11	5.21 centimeters Standard Deviation 0.30	5.08 centimeters Standard Deviation 0.79
Mean Values of Echocardiography Parameters LVPWT, Baseline, n = 219, 233	1.05 centimeters Standard Deviation 0.17	1.05 centimeters Standard Deviation 0.17
Mean Values of Echocardiography Parameters LVPWT, Year 1, n = 170, 186	1.02 centimeters Standard Deviation 0.17	1.01 centimeters Standard Deviation 0.16
Mean Values of Echocardiography Parameters LVPWT, Year 2, n= 135, 147	1.01 centimeters Standard Deviation 0.13	0.99 centimeters Standard Deviation 0.14
Mean Values of Echocardiography Parameters LVPWT, Year 3, n = 74, 81	1.01 centimeters Standard Deviation 0.17	1.00 centimeters Standard Deviation 0.13
Mean Values of Echocardiography Parameters LVPWT, Year 4, n = 2,11	1.08 centimeters Standard Deviation 0.13	0.92 centimeters Standard Deviation 0.16
Mean Values of Echocardiography Parameters IVSWT, Baseline, n = 219, 233	1.18 centimeters Standard Deviation 0.24	1.20 centimeters Standard Deviation 0.28
Mean Values of Echocardiography Parameters IVSWT, Year 1, n = 170, 186	1.17 centimeters Standard Deviation 0.23	1.13 centimeters Standard Deviation 0.24
Mean Values of Echocardiography Parameters IVSWT, Year 2, n = 135, 147	1.12 centimeters Standard Deviation 0.21	1.11 centimeters Standard Deviation 0.20
Mean Values of Echocardiography Parameters IVSWT, Year 3, n = 74, 81	1.14 centimeters Standard Deviation 0.25	1.12 centimeters Standard Deviation 0.22
Mean Values of Echocardiography Parameters IVSWT, Year 4, n = 2, 11	1.30 centimeters Standard Deviation 0.05	1.04 centimeters Standard Deviation 0.20
Mean Values of Echocardiography Parameters LVESD, Baseline, n = 219, 233	2.85 centimeters Standard Deviation 0.58	2.74 centimeters Standard Deviation 0.66
Mean Values of Echocardiography Parameters LVESD, Year 1, n = 170, 186	2.76 centimeters Standard Deviation 0.56	2.73 centimeters Standard Deviation 0.62
Mean Values of Echocardiography Parameters LVESD, Year 2, n = 135, 147	2.78 centimeters Standard Deviation 0.58	2.75 centimeters Standard Deviation 0.68
Mean Values of Echocardiography Parameters LVESD, Year 3, n = 74, 81	2.88 centimeters Standard Deviation 0.75	2.67 centimeters Standard Deviation 0.59
Mean Values of Echocardiography Parameters LVESD, Year 4, n = 2, 11	2.93 centimeters Standard Deviation 0.22	2.84 centimeters Standard Deviation 0.57
Mean Values of Echocardiography Parameters LVRWT, Baseline, n = 219, 233	0.42 centimeters Standard Deviation 0.08	0.43 centimeters Standard Deviation 0.09
Mean Values of Echocardiography Parameters LVRWT, Year 1, n = 170, 186	0.42 centimeters Standard Deviation 0.08	0.41 centimeters Standard Deviation 0.08
Mean Values of Echocardiography Parameters LVRWT, Year 2, n = 135, 147	0.41 centimeters Standard Deviation 0.06	0.41 centimeters Standard Deviation 0.07
Mean Values of Echocardiography Parameters LVRWT, Year 3, n = 74, 81	0.41 centimeters Standard Deviation 0.09	0.42 centimeters Standard Deviation 0.07
Mean Values of Echocardiography Parameters LVRWT, Year 4, n = 2, 11	0.41 centimeters Standard Deviation 0.03	0.37 centimeters Standard Deviation 0.07

SECONDARY outcome

Timeframe: Baseline, Year 1, Year 2, Year 3, and Year 4.

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.

Outcome measures

Outcome measures
Measure	Early Epoetin Beta Therapy n=287 Participants Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=290 Participants Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Mean Values of Body Surface Area BSA, Year 2, n = 224, 234	1.82 Square meter Standard Deviation 0.21	1.77 Square meter Standard Deviation 0.19
Mean Values of Body Surface Area BSA, Baseline, n = 287, 290	1.83 Square meter Standard Deviation 0.22	1.79 Square meter Standard Deviation 0.20
Mean Values of Body Surface Area BSA, Year 1, n = 257, 261	1.83 Square meter Standard Deviation 0.22	1.77 Square meter Standard Deviation 0.23
Mean Values of Body Surface Area BSA, Year 3, n = 116, 121	1.82 Square meter Standard Deviation 0.21	1.72 Square meter Standard Deviation 0.19
Mean Values of Body Surface Area BSA, Year 4, n = 4, 11	1.96 Square meter Standard Deviation 0.21	1.76 Square meter Standard Deviation 0.22

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	Early Epoetin Beta Therapy n=301 Participants Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=302 Participants Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Mean Change From Baseline in the Scores of Each of The Eight Health Scales of Quality of Life Based on Short Form-36 (SF-36) Questionnaire General Health, Year 1	4.1 units on a scale Standard Error 1.01	-0.1 units on a scale Standard Error 0.99
Mean Change From Baseline in the Scores of Each of The Eight Health Scales of Quality of Life Based on Short Form-36 (SF-36) Questionnaire General Health, Year 2	2.3 units on a scale Standard Error 1.14	-1.9 units on a scale Standard Error 1.08
Mean Change From Baseline in the Scores of Each of The Eight Health Scales of Quality of Life Based on Short Form-36 (SF-36) Questionnaire Mental Health, Year 1	2.7 units on a scale Standard Error 0.98	-2.1 units on a scale Standard Error 0.96
Mean Change From Baseline in the Scores of Each of The Eight Health Scales of Quality of Life Based on Short Form-36 (SF-36) Questionnaire Mental Health, Year 2	2.0 units on a scale Standard Error 1.07	-0.4 units on a scale Standard Error 1.02
Mean Change From Baseline in the Scores of Each of The Eight Health Scales of Quality of Life Based on Short Form-36 (SF-36) Questionnaire Physical Function, Year 1	3.5 units on a scale Standard Error 1.1	-2.1 units on a scale Standard Error 1.1
Mean Change From Baseline in the Scores of Each of The Eight Health Scales of Quality of Life Based on Short Form-36 (SF-36) Questionnaire Physical Function, Year 2	-2.5 units on a scale Standard Error 1.33	-2.5 units on a scale Standard Error 1.27
Mean Change From Baseline in the Scores of Each of The Eight Health Scales of Quality of Life Based on Short Form-36 (SF-36) Questionnaire Physical Role, Year 1	2.6 units on a scale Standard Error 2.23	-5.5 units on a scale Standard Error 2.20
Mean Change From Baseline in the Scores of Each of The Eight Health Scales of Quality of Life Based on Short Form-36 (SF-36) Questionnaire Physical Role, Year 2	-2.3 units on a scale Standard Error 2.59	-7.3 units on a scale Standard Error 2.47
Mean Change From Baseline in the Scores of Each of The Eight Health Scales of Quality of Life Based on Short Form-36 (SF-36) Questionnaire Social Function, Year 1	1.8 units on a scale Standard Error 1.23	-3.0 units on a scale Standard Error 1.21
Mean Change From Baseline in the Scores of Each of The Eight Health Scales of Quality of Life Based on Short Form-36 (SF-36) Questionnaire Social Function, Year 2	-0.1 units on a scale Standard Error 1.44	-3.0 units on a scale Standard Error 1.37
Mean Change From Baseline in the Scores of Each of The Eight Health Scales of Quality of Life Based on Short Form-36 (SF-36) Questionnaire Vitality Function, Year 1	3.9 units on a scale Standard Error 0.97	-0.6 units on a scale Standard Error 0.95
Mean Change From Baseline in the Scores of Each of The Eight Health Scales of Quality of Life Based on Short Form-36 (SF-36) Questionnaire Vitality Function, Year 2	2.8 units on a scale Standard Error 1.10	-1.0 units on a scale Standard Error 1.05
Mean Change From Baseline in the Scores of Each of The Eight Health Scales of Quality of Life Based on Short Form-36 (SF-36) Questionnaire Bodily Pain, Year 1	-0.2 units on a scale Standard Error 1.37	-2.1 units on a scale Standard Error 1.35
Mean Change From Baseline in the Scores of Each of The Eight Health Scales of Quality of Life Based on Short Form-36 (SF-36) Questionnaire Bodily Pain, Year 2	-2.0 units on a scale Standard Error 1.53	-1.2 units on a scale Standard Error 1.46
Mean Change From Baseline in the Scores of Each of The Eight Health Scales of Quality of Life Based on Short Form-36 (SF-36) Questionnaire Emotional Role, Year 1	0.4 units on a scale Standard Error 2.17	-4.3 units on a scale Standard Error 2.14
Mean Change From Baseline in the Scores of Each of The Eight Health Scales of Quality of Life Based on Short Form-36 (SF-36) Questionnaire Emotional Role, Year 2	-0.1 units on a scale Standard Error 2.51	-2.2 units on a scale Standard Error 2.42

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Early Epoetin Beta Therapy n=300 Participants Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=302 Participants Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs Tricyclic Antidepressants	1 participants	0 participants
Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs No. of participants with at least one Tt	287 participants	282 participants
Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs Calcium Channel Blocking Agents	201 participants	204 participants
Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs Loop Diuretics	183 participants	180 participants
Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs Angiotensin-Converting Enzyme Inhibitors	158 participants	153 participants
Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs Beta-Adrenoceptor Blocking Agents	169 participants	136 participants
Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs Angiotensin-II Receptor Antagonists	89 participants	96 participants
Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs Alpha-Adrenoreceptor Antagonists	87 participants	73 participants
Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs Antihypertensive Agents	55 participants	52 participants
Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs Thiazide And Related Diuretics	44 participants	40 participants
Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs Antianginal Agents	6 participants	5 participants
Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs Potassium Sparing Diuretics	4 participants	7 participants
Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs Aldosterone Antagonists	2 participants	5 participants
Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs Cardiac Glycosides	1 participants	1 participants
Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs Diuretics	2 participants	0 participants
Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs Supplements	1 participants	1 participants
Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs Calcium Compounds And Regulators	0 participants	1 participants
Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs Miscellaneous Drugs	0 participants	1 participants

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	Early Epoetin Beta Therapy n=206 Participants Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=208 Participants Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Number of Participants With Marked Laboratory Abnormalities Platelets - High; n = 206, 208	5 participants	0 participants
Number of Participants With Marked Laboratory Abnormalities Platelets - Low; n = 206, 208	13 participants	15 participants
Number of Participants With Marked Laboratory Abnormalities Creatinine - High; n = 206, 208	140 participants	128 participants
Number of Participants With Marked Laboratory Abnormalities Albumin - Low; n = 201, 205	6 participants	9 participants
Number of Participants With Marked Laboratory Abnormalities Phosphate - High; n = 206, 208	164 participants	150 participants
Number of Participants With Marked Laboratory Abnormalities Phosphate - Low; n = 206, 208	22 participants	23 participants
Number of Participants With Marked Laboratory Abnormalities Potassium - High; n = 206, 208	47 participants	46 participants
Number of Participants With Marked Laboratory Abnormalities Potassium - Low; n = 206, 208	4 participants	6 participants

Adverse Events

Early Epoetin Beta Therapy

Serious events: 158 serious events

Other events: 243 other events

Deaths: 0 deaths

Late Epoetin Beta Therapy

Serious events: 145 serious events

Other events: 228 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Roche Trial Information Hotline

F. Hoffmann-La Roche AG

Phone: +41 61 6878333

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Early Epoetin Beta Therapy n=300 participants at risk Participants received immediate epoetin beta therapy starting at 2000 IU, subcutaneously once weekly up to four years to reach a target Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.	Late Epoetin Beta Therapy n=302 participants at risk Participants received epoetin beta treatment starting at 2000 IU, subcutaneously once weekly up to four years only when a decline in Hb levels to \<10.5 g/dL had occurred in order to reach a target Hb of 10.5-11.5 g/dL.
Renal and urinary disorders Renal Failure	31.0% 93/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	28.8% 87/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Renal and urinary disorders Renal Failure Chronic	11.0% 33/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	15.2% 46/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Renal and urinary disorders Renal Impairment	9.0% 27/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	7.6% 23/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Infections and infestations Upper respiratory tract infection	5.3% 16/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	9.3% 28/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Infections and infestations Urinary tract infection	8.7% 26/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	9.6% 29/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Infections and infestations Nasopharyngitis	8.0% 24/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	7.6% 23/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Infections and infestations Influenza	8.7% 26/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	4.0% 12/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Infections and infestations Bronchitis	4.0% 12/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	5.3% 16/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Infections and infestations Bronchitis Acute	5.0% 15/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	2.0% 6/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Vascular disorders Hypertension	29.7% 89/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	19.2% 58/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Vascular disorders Hypotension	4.3% 13/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	5.3% 16/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Gastrointestinal disorders Diarrhoea	8.0% 24/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	8.3% 25/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Gastrointestinal disorders Constipation	7.3% 22/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	6.3% 19/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Gastrointestinal disorders Nausea	5.0% 15/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	4.6% 14/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Gastrointestinal disorders Vomiting	5.0% 15/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	4.0% 12/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Musculoskeletal and connective tissue disorders Back pain	7.3% 22/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	10.9% 33/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Musculoskeletal and connective tissue disorders Arthralgia	7.0% 21/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	6.3% 19/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Musculoskeletal and connective tissue disorders Pain in extremity	6.0% 18/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	5.3% 16/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Musculoskeletal and connective tissue disorders Muscle cramp	3.0% 9/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	5.3% 16/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Metabolism and nutrition disorders Hyperkalaemia	9.3% 28/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	9.9% 30/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Metabolism and nutrition disorders Hyperphosphataemia	9.0% 27/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	7.3% 22/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Metabolism and nutrition disorders Gout	5.0% 15/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	5.3% 16/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
General disorders Oedema Peripheral	6.7% 20/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	3.6% 11/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
General disorders Asthenia	5.3% 16/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	5.6% 17/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
General disorders Fatigue	4.7% 14/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	5.6% 17/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Nervous system disorders Headache	10.0% 30/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	5.0% 15/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Nervous system disorders Dizziness	6.0% 18/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	4.3% 13/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Skin and subcutaneous tissue disorders Pruritis	9.0% 27/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	6.0% 18/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Respiratory, thoracic and mediastinal disorders Cough	6.7% 20/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	5.3% 16/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Psychiatric disorders Insomnia	4.0% 12/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	7.6% 23/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Investigations Blood Pressure Increased	6.3% 19/300 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	4.3% 13/302 • Up to 4 years An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.