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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT00321919
Collaborator
(none)
605
Enrollment
93
Locations
2
Arms
53
Duration (Months)
6.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate whether anemia prevention with NeoRecormon has an additional impact on reducing cardiovascular risk over conventional anemia treatment in patients mostly with stage IV chronic kidney disease and renal anemia. The anticipated time on study treatment is 2+ years and the target sample size is 500+ individuals.

Condition or Disease Intervention/Treatment Phase
  • Drug: epoetin beta [NeoRecormon]
  • Drug: epoetin beta [NeoRecormon]
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
605 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Open-label Study of the Effect of NeoRecormon on Reduction of Cardiovascular Risk in Patients With Chronic Renal Anemia Who Are Not on Renal Replacement Therapy.
Study Start Date :
Jul 1, 2000
Actual Primary Completion Date :
Oct 1, 2004
Actual Study Completion Date :
Dec 1, 2004

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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 Hb level of 13-15 g/dL; with an individual Hb increase of at least 2 g/dL within approximately 3 months.

Drug: epoetin beta [NeoRecormon]
Participants in the early treatment group immediately started epoetin beta treatment to reach a target Hb level of 13-15 g/dL at the end of the correction phase.
Active Comparator: 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 had occurred in order to reach a target Hb of 10.5-11.5 g/dL.

Drug: epoetin beta [NeoRecormon]
Participants in the late treatment Group started epoetin beta treatment once a decline in Hb level to <10.5 g/dL had occurred.

Outcome Measures

Primary Outcome Measures

  1. Median Time to First Cardiovascular Event [Up to 4 years]

    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.

Secondary Outcome Measures

  1. Median Time to Death Due to Cardiovascular Events [Up to 4 years]

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

  2. Number of Participants Who Died Due to Cardiovascular Events [Up to 4 years]

    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.

  3. Median Time to Death Due to All Causes [Up to 4 years]

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

  4. Number of Participants Who Died Due to All Causes [Up to 4 years]

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

  5. Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL) [Up to 4 years]

    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.

  6. Median Time to First Cardiovascular Intervention [Up to 4 years]

    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.

  7. Total Number of Cardiovascular Intervention [Up to 4 years]

    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.

  8. Median Time to First Hospitalization Due to Cardiovascular Events [Up to 4 years]

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

  9. Duration of Hospitalization for Cardiovascular Events [Up to 4 years]

    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.

  10. Mean Change From Baseline in Left Ventricular Mass Index (LVMI) [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.

  11. Mean Change From Baseline in Left Ventricular Ejection Fraction (LVEF) and Fractional Myocardial Shortening (FS) [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.

  12. Mean Change From Baseline in Left Ventricular Volume (LV Volume ) [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.

  13. Mean Values of Echocardiography Parameters [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.

  14. Mean Values of Body Surface Area [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.

  15. 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 [Baseline, Year 1, and Year 2]

    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.

  16. Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs [Up to 4 years]

    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.

  17. Number of Participants With Marked Laboratory Abnormalities [Baseline, every 3 months up to 4 years]

    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).

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • adult patients >=18 years of age;

  • chronic renal anemia;

  • not receiving renal replacement therapy.

Exclusion Criteria:

  • women who are pregnant or lactating;

  • previous treatment with erythropoietin or other erythropoietic substance;

  • blood transfusion within the last 3 months;

  • need for dialysis expected in the next 6 months;

  • administration of another investigational drug within 30 days preceding study start, or during the study.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Linz Austria 4020
2 St Pölten Austria 3100
3 Bruxelles Belgium 1070
4 Bruxelles Belgium 1090
5 Edegem Belgium 2650
6 Brno Czech Republic 625 00
7 Havirov Czech Republic 736 01
8 Olomouc Czech Republic 775 20
9 Ostrava Czech Republic 708 52
10 Fredericia Denmark 7000
11 Herlev Denmark 2730
12 Holbaek Denmark 4300
13 Roskilde Denmark 4000
14 Jyväskylä Finland 40620
15 Tampere Finland 33521
16 Amiens France 80054
17 Angouleme France 16470
18 Bordeaux France 33000
19 Boulogne France 62321
20 Colmar France 68024
21 Lyon France 69437
22 Montpellier France 34295
23 Paris France 75743
24 Saint Brieuc France 22023
25 Troyes France 10003
26 Vandoeuvre-les-nancy France 54511
27 Berlin Germany 13353
28 Villingen-schwenningen Germany 78054
29 Würzburg Germany 97072
30 Athens Greece 115 27
31 Thessaloniki Greece 546 42
32 Veria Greece 59100
33 Hong Kong Hong Kong
34 Dublin Ireland 9
35 Bologna Italy 40138
36 Busto Arsizio Italy 21052
37 Cagliari Italy 09134
38 Cinisello Balsamo Italy 20092
39 Lecco Italy 23900
40 Napoli Italy 80131
41 Padova Italy 35128
42 Parma Italy 43100
43 Pavia Italy 27100
44 Roma Italy 00144
45 Roma Italy 00146
46 Roma Italy 00152
47 San Giovanni Rotondo Italy 71013
48 Trieste Italy 34125
49 Vimercate Italy 20059
50 Cuernavaca Mexico 62448
51 Tijuana Mexico 44650
52 Oslo Norway 0407
53 Gdansk Poland 80-211
54 Kielce Poland 25-736
55 Krakow Poland 31-501
56 Wroclaw Poland 50-417
57 Almada Portugal 2800
58 Carnaxide Portugal 2799-523
59 Lisboa Portugal 1800-083
60 Porto Portugal 4200-319
61 Moscow Russian Federation 123182
62 Moscow Russian Federation 125101
63 Moscow Russian Federation
64 St Petersburg Russian Federation 195067
65 St Petersburg Russian Federation 197110
66 Barcelona Spain 08035
67 Las Palmas de Gran Canaria Spain 35020
68 Madrid Spain 28007
69 Madrid Spain 28046
70 Valencia Spain 46009
71 Boras Sweden 50182
72 Helsingborg Sweden 25187
73 Jonkoping Sweden 55185
74 Karlstad Sweden 65185
75 Norrkoping Sweden 60182
76 Oerebro Sweden 70185
77 Stockholm Sweden 17176
78 Sundsvall Sweden 85186
79 Taichung Taiwan 407
80 Tainan Taiwan 701
81 Taipei Taiwan 100
82 Taoyuan Taiwan 333
83 Bangkok Thailand 10700
84 Chiang Mai Thailand 50200
85 Ankara Turkey 06100
86 Istanbul Turkey 34390
87 Izmir Turkey 35100
88 Belfast United Kingdom BT9 7AB
89 London United Kingdom SE22 8PT
90 Newcastle Upon Tyne United Kingdom NE7 7DN
91 Salford United Kingdom M6 8HD
92 Southampton United Kingdom SO16 6YD
93 Surrey United Kingdom SM5 1AA

Sponsors and Collaborators

  • Hoffmann-La Roche

Investigators

  • Study Chair: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00321919
Other Study ID Numbers:
  • BA16169
First Posted:
May 4, 2006
Last Update Posted:
Jun 29, 2016
Last Verified:
May 1, 2016
Additional relevant MeSH terms:
Anemia
Epoetin Alfa

Study Results

Participant Flow

Recruitment Details This study was conducted from 26 July 2000 to 13 December 2004 at 94 centers in 21 countries.
Pre-assignment Detail 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.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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. 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.
Period Title: Overall Study
STARTED 301 302
COMPLETED 226 250
NOT COMPLETED 75 52

Baseline Characteristics

Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy Total
Arm/Group Description 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. 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 of all reporting groups
Overall Participants 301 302 603
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
59.3
(14.57)
58.8
(13.73)
59.0
(14.14)
Sex: Female, Male (Count of Participants)
Female
130
43.2%
148
49%
278
46.1%
Male
171
56.8%
154
51%
325
53.9%

Outcome Measures

1. Primary Outcome
Title Median Time to First Cardiovascular Event
Description 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

Outcome Measure Data

Analysis Population Description
The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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. 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.
Measure Participants 301 302
Median (Inter-Quartile Range) [days]
NA
NA
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments The null hypothesis stated that there was no difference with regard to the event-free distribution of the combined endpoint of all protocol specified cardiovascular events between Early Epoetin beta therapy and Late Epoetin beta therapy groups.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.2036
Comments
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.778976
Confidence Interval (2-Sided) 95%
0.53 to 1.14
Parameter Dispersion Type:
Value:
Estimation Comments The Cox regression model was used to estimate the relative risk of the time to first cardiovascular event in Late Epoetin beta therapy group compared to the Early Epoetin beta therapy group.
2. Secondary Outcome
Title Median Time to Death Due to Cardiovascular Events
Description 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

Outcome Measure Data

Analysis Population Description
The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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. 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.
Measure Participants 301 302
Median (Inter-Quartile Range) [days]
NA
NA
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4833
Comments
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.744575
Confidence Interval (2-Sided) 95%
0.33 to 1.70
Parameter Dispersion Type:
Value:
Estimation Comments The Cox regression model was used to estimate the relative risk of an event of the time to death due to cardiovascular reasons in Late Epoetin beta therapy group compared to the Early Epoetin beta therapy group.
3. Secondary Outcome
Title Number of Participants Who Died Due to Cardiovascular Events
Description 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

Outcome Measure Data

Analysis Population Description
The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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. 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.
Measure Participants 301 302
Total Cardiovascular Death Events
8
2.7%
6
2%
Cardiac Failure
1
0.3%
2
0.7%
Cardiac Failure Acute
1
0.3%
2
0.7%
Acute Myocardial Infarction
1
0.3%
1
0.3%
Angina Pectoris
1
0.3%
0
0%
Arrhythmia
1
0.3%
0
0%
Cardiac Arrest
1
0.3%
0
0%
Cardio-Respiratory Arrest
1
0.3%
0
0%
Cardiopulmonary Failure
1
0.3%
0
0%
Myocardial Infarction
0
0%
1
0.3%
4. Secondary Outcome
Title Median Time to Death Due to All Causes
Description 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

Outcome Measure Data

Analysis Population Description
The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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. 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.
Measure Participants 301 302
Median (Inter-Quartile Range) [days]
NA
NA
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1391
Comments
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.658259
Confidence Interval (2-Sided) 95%
0.38 to 1.15
Parameter Dispersion Type:
Value:
Estimation Comments The Cox regression model was used to estimate the relative risk of the time to death for all causes in Late Epoetin beta therapy group compared to the Early Epoetin beta therapy treatment group.
5. Secondary Outcome
Title Number of Participants Who Died Due to All Causes
Description Number of participants who died due to all causes are presented in table below.
Time Frame Up to 4 years

Outcome Measure Data

Analysis Population Description
The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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. 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.
Measure Participants 301 302
Total Death Events for All-cause
31
10.3%
21
7%
Sudden Death
4
1.3%
2
0.7%
Cerebrovascular Accident
2
0.7%
2
0.7%
Cardiac Failure
1
0.3%
2
0.7%
Cardiac Failure Acute
1
0.3%
2
0.7%
Sepsis
1
0.3%
2
0.7%
Acute Myocardial Infarction
1
0.3%
1
0.3%
Bronchopneumonia
1
0.3%
1
0.3%
Respiratory Failure
1
0.3%
1
0.3%
Septic Shock
2
0.7%
0
0%
Acute Heart Failure
1
0.3%
0
0%
Acute Respiratory Failure
0
0%
1
0.3%
Angina Pectoris
1
0.3%
0
0%
Arrhythmia
1
0.3%
0
0%
Cardiac Arrest
1
0.3%
0
0%
Cardio-Respiratory Arrest
1
0.3%
0
0%
Cardiopulmonary Failure
1
0.3%
0
0%
Cerebral Infarction
1
0.3%
0
0%
Clostridial Infection
1
0.3%
0
0%
Colon Cancer Metastatic
0
0%
1
0.3%
Embolic Stroke
1
0.3%
0
0%
Intestinal Infarction
0
0%
1
0.3%
Intestinal Ischaemia
0
0%
1
0.3%
Laryngeal Cancer
1
0.3%
0
0%
Lung Neoplasm Malignant
0
0%
1
0.3%
Metastases To Lung
1
0.3%
0
0%
Metastatic Neoplasm
1
0.3%
0
0%
Myocardial Infarction
0
0%
1
0.3%
Oesophageal Carcinoma
1
0.3%
0
0%
Peripheral Vascular Disorder
1
0.3%
0
0%
Pneumonia
0
0%
1
0.3%
Pulmonary Embolism
0
0%
1
0.3%
Renal Failure
1
0.3%
0
0%
Unevaluable Event
1
0.3%
0
0%
Uraemic Encephalopathy
1
0.3%
0
0%
6. Secondary Outcome
Title Number of Participants Experiencing Worsening of New York Heart Association (NYHA) Class (CL) of Chronic Heart Failure From Baseline (BL)
Description 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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. 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.
Measure Participants 167 149
From CL 0 (BL) to CL 0; n = 167, 149
49
16.3%
42
13.9%
From CL 0 (BL) to CL I; n = 167, 149
7
2.3%
4
1.3%
From CL 0 (BL) to CL II; n = 167, 149
7
2.3%
7
2.3%
From CL 0 (BL) to CL III; n = 167, 149
2
0.7%
1
0.3%
From CL 0 (BL) to CL IV; n = 167, 149
0
0%
0
0%
From CL I (BL) to CL 0; n = 37, 43
1
0.3%
0
0%
From CL I (BL) to CL I; n = 37, 43
28
9.3%
34
11.3%
From CL I (BL) to CL II; n = 37, 43
5
1.7%
4
1.3%
From CL I (BL) to CL III; n = 37, 43
0
0%
0
0%
From CL I (BL) to CL IV; n = 37, 43
0
0%
0
0%
From CL II (BL) to CL 0; n = 53, 44
0
0%
0
0%
From CL II (BL) to CL I; n = 53, 44
5
1.7%
1
0.3%
From CL II (BL) to CL II; n = 53, 44
39
13%
37
12.3%
From CL II (BL) to CL III; n = 53, 44
2
0.7%
4
1.3%
From CL II (BL) to CL IV; n = 53, 44
0
0%
0
0%
From CL III (BL) to CL 0; n = 0, 0
0
0%
0
0%
From CL III (BL)to CL I; n = 0, 0
0
0%
0
0%
From CL III (BL)to CL II; n = 0, 0
0
0%
0
0%
From CL III (BL)to CL III; n = 0, 0
0
0%
0
0%
From CL III (BL)to CL IV; n = 0, 0
0
0%
0
0%
From CL IV (BL)to CL 0; n = 0, 0
0
0%
0
0%
From CL IV (BL)to CL I; n = 0, 0
0
0%
0
0%
From CL IV (BL)to CL II; n = 0, 0
0
0%
0
0%
From CL IV (BL)to CL III; n = 0, 0
0
0%
0
0%
From CL IV (BL)to CL IV; n = 0, 0
0
0%
0
0%
7. Secondary Outcome
Title Median Time to First Cardiovascular Intervention
Description 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

Outcome Measure Data

Analysis Population Description
The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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. 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.
Measure Participants 301 302
Median (Inter-Quartile Range) [days]
NA
NA
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.4985
Comments
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.804594
Confidence Interval (2-Sided) 95%
0.43 to 1.51
Parameter Dispersion Type:
Value:
Estimation Comments The Cox regression model was used to estimate the relative risk of time to first cardiovascular intervention in Late Epoetin beta therapy group compared to the Early Epoetin beta therapy group
8. Secondary Outcome
Title Total Number of Cardiovascular Intervention
Description 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

Outcome Measure Data

Analysis Population Description
The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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. 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.
Measure Participants 301 302
Number [number of cardiovascular intervention]
21
18
9. Secondary Outcome
Title Median Time to First Hospitalization Due to Cardiovascular Events
Description 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

Outcome Measure Data

Analysis Population Description
The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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 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.
Measure Participants 301 302
Median (Inter-Quartile Range) [days]
NA
NA
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3419
Comments
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.82046
Confidence Interval (2-Sided) 95%
0.55 to 1.23
Parameter Dispersion Type:
Value:
Estimation Comments The Cox regression model was used to estimate the relative risk of the time to first hospitalization for cardiovascular reasons in Late Epoetin beta therapy group compared to the Early Epoetin beta therapy group.
10. Secondary Outcome
Title Duration of Hospitalization for Cardiovascular Events
Description 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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. 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.
Measure Participants 171 161
Mean (Standard Deviation) [days]
33.0
(42.0)
28.2
(33.7)
11. Secondary Outcome
Title Mean Change From Baseline in Left Ventricular Mass Index (LVMI)
Description 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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. 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.
Measure Participants 219 232
LVMI, Baseline; n = 219, 232
120.32
(35.03)
117.97
(34.34)
LVMI, Week 12; n = 171, 186
-5.06
(24.81)
-2.87
(25.16)
LVMI, Week 24; n = 136, 146
-6.58
(26.94)
-7.59
(25.59)
LVMI, Week 36; n = 74, 81
-1.30
(36.04)
-7.53
(34.37)
LVMI, Week 48; n = 2, 11
2.00
(2.83)
-27.27
(29.47)
12. Secondary Outcome
Title Mean Change From Baseline in Left Ventricular Ejection Fraction (LVEF) and Fractional Myocardial Shortening (FS)
Description 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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. 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.
Measure Participants 219 233
LVEF, Baseline; n = 219, 233
81.31
(7.24)
81.95
(7.75)
LVEF, Week 12; n = 170, 186
-0.08
(7.32)
0.08
(7.34)
LVEF, Week 24; n = 135, 147
-0.47
(6.82)
-0.23
(7.01)
LVEF, Week 36; n = 74, 81
-0.61
(8.61)
0.24
(6.75)
LVEF, Week 48; n = 2,11
-0.46
(2.92)
2.80
(8.12)
FS, Baseline; n = 219, 232
43.67
(7.12)
44.67
(7.86)
FS, Week 12; n = 196, 212
0.13
(6.79)
0.08
(7.34)
FS, Week 24; n = 174, 192
0.11
(7.10)
-0.19
(7.40)
FS, Week 36; n = 98, 105
0.05
(8.16)
0.70
(7.80)
FS, Week 48; n = 4,12
1.00
(2.83)
3.00
(8.58)
13. Secondary Outcome
Title Mean Change From Baseline in Left Ventricular Volume (LV Volume )
Description 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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. 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.
Measure Participants 218 232
LV Volume, Baseline; n = 218, 232
67.73
(19.20)
65.11
(19.24)
LV Volume, Week 12; n = 170, 186
-2.83
(15.90)
3.15
(15.46)
LV Volume, Week 24; n = 134, 146
-0.69
(16.44)
2.62
(18.56)
LV Volume, Week 36; n = 72, 80
3.34
(24.29)
4.05
(19.08)
LV Volume, Week 48; n = 2, 11
14.48
(11.52)
7.91
(23.37)
14. Secondary Outcome
Title Mean Values of Echocardiography Parameters
Description 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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. 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.
Measure Participants 219 233
LVEDD, Baseline, n = 219, 233
5.05
(0.67)
4.91
(0.68)
LVEDD, Year 1, n = 170, 186
4.93
(0.62)
4.94
(0.65)
LVEDD, Year 2, n = 135, 147
4.95
(0.63)
4.93
(0.72)
LVEDD, Year 3, n = 74, 81
5.09
(0.71)
4.88
(0.59)
LVEDD, Year 4, n = 2,11
5.21
(0.30)
5.08
(0.79)
LVPWT, Baseline, n = 219, 233
1.05
(0.17)
1.05
(0.17)
LVPWT, Year 1, n = 170, 186
1.02
(0.17)
1.01
(0.16)
LVPWT, Year 2, n= 135, 147
1.01
(0.13)
0.99
(0.14)
LVPWT, Year 3, n = 74, 81
1.01
(0.17)
1.00
(0.13)
LVPWT, Year 4, n = 2,11
1.08
(0.13)
0.92
(0.16)
IVSWT, Baseline, n = 219, 233
1.18
(0.24)
1.20
(0.28)
IVSWT, Year 1, n = 170, 186
1.17
(0.23)
1.13
(0.24)
IVSWT, Year 2, n = 135, 147
1.12
(0.21)
1.11
(0.20)
IVSWT, Year 3, n = 74, 81
1.14
(0.25)
1.12
(0.22)
IVSWT, Year 4, n = 2, 11
1.30
(0.05)
1.04
(0.20)
LVESD, Baseline, n = 219, 233
2.85
(0.58)
2.74
(0.66)
LVESD, Year 1, n = 170, 186
2.76
(0.56)
2.73
(0.62)
LVESD, Year 2, n = 135, 147
2.78
(0.58)
2.75
(0.68)
LVESD, Year 3, n = 74, 81
2.88
(0.75)
2.67
(0.59)
LVESD, Year 4, n = 2, 11
2.93
(0.22)
2.84
(0.57)
LVRWT, Baseline, n = 219, 233
0.42
(0.08)
0.43
(0.09)
LVRWT, Year 1, n = 170, 186
0.42
(0.08)
0.41
(0.08)
LVRWT, Year 2, n = 135, 147
0.41
(0.06)
0.41
(0.07)
LVRWT, Year 3, n = 74, 81
0.41
(0.09)
0.42
(0.07)
LVRWT, Year 4, n = 2, 11
0.41
(0.03)
0.37
(0.07)
15. Secondary Outcome
Title Mean Values of Body Surface Area
Description 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.

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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. 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.
Measure Participants 287 290
BSA, Baseline, n = 287, 290
1.83
(0.22)
1.79
(0.20)
BSA, Year 1, n = 257, 261
1.83
(0.22)
1.77
(0.23)
BSA, Year 2, n = 224, 234
1.82
(0.21)
1.77
(0.19)
BSA, Year 3, n = 116, 121
1.82
(0.21)
1.72
(0.19)
BSA, Year 4, n = 4, 11
1.96
(0.21)
1.76
(0.22)
16. Secondary Outcome
Title 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
Description 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

Outcome Measure Data

Analysis Population Description
The ITT population included all participants randomized according to their randomized treatment group, regardless of the treatment actually received.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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. 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.
Measure Participants 301 302
General Health, Year 1
4.1
(1.01)
-0.1
(0.99)
General Health, Year 2
2.3
(1.14)
-1.9
(1.08)
Mental Health, Year 1
2.7
(0.98)
-2.1
(0.96)
Mental Health, Year 2
2.0
(1.07)
-0.4
(1.02)
Physical Function, Year 1
3.5
(1.1)
-2.1
(1.1)
Physical Function, Year 2
-2.5
(1.33)
-2.5
(1.27)
Physical Role, Year 1
2.6
(2.23)
-5.5
(2.20)
Physical Role, Year 2
-2.3
(2.59)
-7.3
(2.47)
Social Function, Year 1
1.8
(1.23)
-3.0
(1.21)
Social Function, Year 2
-0.1
(1.44)
-3.0
(1.37)
Vitality Function, Year 1
3.9
(0.97)
-0.6
(0.95)
Vitality Function, Year 2
2.8
(1.10)
-1.0
(1.05)
Bodily Pain, Year 1
-0.2
(1.37)
-2.1
(1.35)
Bodily Pain, Year 2
-2.0
(1.53)
-1.2
(1.46)
Emotional Role, Year 1
0.4
(2.17)
-4.3
(2.14)
Emotional Role, Year 2
-0.1
(2.51)
-2.2
(2.42)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments Mean Change from Baseline in the Score of General health scale of Quality of life for Year 1.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0029
Comments
Method ANCOVA
Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments Mean Change from Baseline in the Score of General health scale of Quality of life for Year 2
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0081
Comments
Method ANCOVA
Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments Mean Change from Baseline in the Score of Mental health scale of Quality of life for Year 1
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0005
Comments
Method ANCOVA
Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments Mean Change from Baseline in the Score of Mental Health scale of Quality of life for Year 2
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0965
Comments
Method ANCOVA
Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments Mean Change from Baseline in the Score of Physical function scale of Quality of life for Year 1
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0004
Comments
Method ANCOVA
Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments Mean Change from Baseline in the Score of Physical function scale of Quality of life for Year 2
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9864
Comments
Method ANCOVA
Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments Mean Change from Baseline in the Score of Physical Role scale of Quality of life for Year 1
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0097
Comments
Method ANCOVA
Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments Mean Change from Baseline in the Score of Physical Role scale of Quality of life for Year 2
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1670
Comments
Method ANCOVA
Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments Mean Change from Baseline in the Score of Social function scale of Quality of life for Year 1
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0058
Comments
Method ANCOVA
Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments Mean Change from Baseline in the Score of Social function scale of Quality of life for Year 2
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1455
Comments
Method ANCOVA
Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments Mean Change from Baseline in the Score of Vitality function scale of Quality of life for Year 1
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0009
Comments
Method ANCOVA
Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments Mean Change from Baseline in the Score of Vitality function scale of Quality of life for Year 2
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.0123
Comments
Method ANCOVA
Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments Mean Change from Baseline in the Score of Bodily pain scale of Quality of life for Year 1
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.3155
Comments
Method ANCOVA
Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments Mean Change from Baseline in the Score of Bodily pain scale of Quality of life for Year 2
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.7076
Comments
Method ANCOVA
Comments
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments Mean Change from Baseline in the Score of Emotional role scale of Quality of life for Year 1
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.1291
Comments
Method ANCOVA
Comments
Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Early Epoetin Beta Therapy, Late Epoetin Beta Therapy
Comments Mean Change from Baseline in the Score of Emotional role scale of Quality of life for Year 2
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5528
Comments
Method ANCOVA
Comments
17. Secondary Outcome
Title Number of Participants on Blood Pressure/Anti-Hypertensive Treatment According to Class Of Drugs
Description 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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. 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.
Measure Participants 300 302
No. of participants with at least one Tt
287
95.3%
282
93.4%
Calcium Channel Blocking Agents
201
66.8%
204
67.5%
Loop Diuretics
183
60.8%
180
59.6%
Angiotensin-Converting Enzyme Inhibitors
158
52.5%
153
50.7%
Beta-Adrenoceptor Blocking Agents
169
56.1%
136
45%
Angiotensin-II Receptor Antagonists
89
29.6%
96
31.8%
Alpha-Adrenoreceptor Antagonists
87
28.9%
73
24.2%
Antihypertensive Agents
55
18.3%
52
17.2%
Thiazide And Related Diuretics
44
14.6%
40
13.2%
Antianginal Agents
6
2%
5
1.7%
Potassium Sparing Diuretics
4
1.3%
7
2.3%
Aldosterone Antagonists
2
0.7%
5
1.7%
Cardiac Glycosides
1
0.3%
1
0.3%
Diuretics
2
0.7%
0
0%
Supplements
1
0.3%
1
0.3%
Calcium Compounds And Regulators
0
0%
1
0.3%
Miscellaneous Drugs
0
0%
1
0.3%
Tricyclic Antidepressants
1
0.3%
0
0%
18. Secondary Outcome
Title Number of Participants With Marked Laboratory Abnormalities
Description 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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. 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.
Measure Participants 206 208
Platelets - High; n = 206, 208
5
1.7%
0
0%
Platelets - Low; n = 206, 208
13
4.3%
15
5%
Creatinine - High; n = 206, 208
140
46.5%
128
42.4%
Albumin - Low; n = 201, 205
6
2%
9
3%
Phosphate - High; n = 206, 208
164
54.5%
150
49.7%
Phosphate - Low; n = 206, 208
22
7.3%
23
7.6%
Potassium - High; n = 206, 208
47
15.6%
46
15.2%
Potassium - Low; n = 206, 208
4
1.3%
6
2%

Adverse Events

Time Frame Up to 4 years
Adverse Event Reporting Description 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.
Arm/Group Title Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Arm/Group Description 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. 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.
All Cause Mortality
Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN)
Serious Adverse Events
Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 158/300 (52.7%) 145/302 (48%)
Blood and lymphatic system disorders
Anaemia 3/300 (1%) 6/302 (2%)
Leukopenia 1/300 (0.3%) 0/302 (0%)
Nephrogenic Anaemia 1/300 (0.3%) 0/302 (0%)
Neutropenia 0/300 (0%) 1/302 (0.3%)
Cardiac disorders
Arrhythmia 16/300 (5.3%) 14/302 (4.6%)
Cardiac Failure Acute 11/300 (3.7%) 19/302 (6.3%)
Myocardial Infarction 13/300 (4.3%) 14/302 (4.6%)
Angina Pectoris 11/300 (3.7%) 4/302 (1.3%)
Cardiac Arrest 2/300 (0.7%) 0/302 (0%)
Cardiac Failure Chronic 0/300 (0%) 1/302 (0.3%)
Cardiac Failure Congestive 0/300 (0%) 1/302 (0.3%)
Cardiopulmonary Failure 1/300 (0.3%) 0/302 (0%)
Coronary Artery Occlusion 1/300 (0.3%) 0/302 (0%)
Coronary Artery Stenosis 1/300 (0.3%) 1/302 (0.3%)
Myocarditis 1/300 (0.3%) 0/302 (0%)
Pericardial Effusion 0/300 (0%) 1/302 (0.3%)
Congenital, familial and genetic disorders
Congenital Cystic Kidney Disease 1/300 (0.3%) 0/302 (0%)
Polycystic Liver Disease 0/300 (0%) 1/302 (0.3%)
Ear and labyrinth disorders
Vestibular Neuronitis 1/300 (0.3%) 0/302 (0%)
Endocrine disorders
Hyperparathyroidism 0/300 (0%) 2/302 (0.7%)
Hyperparathyroidism Secondary 2/300 (0.7%) 0/302 (0%)
Hyperthyroidism 0/300 (0%) 1/302 (0.3%)
Eye disorders
Retinal Detachment 1/300 (0.3%) 1/302 (0.3%)
Cataract 0/300 (0%) 1/302 (0.3%)
Glaucoma 1/300 (0.3%) 0/302 (0%)
Ocular Hypertension 0/300 (0%) 1/302 (0.3%)
Strabismus 0/300 (0%) 1/302 (0.3%)
Vitreous Haemorrhage 0/300 (0%) 1/302 (0.3%)
Gastrointestinal disorders
Peritonitis 4/300 (1.3%) 3/302 (1%)
Abdominal Pain 0/300 (0%) 5/302 (1.7%)
Vomiting 1/300 (0.3%) 4/302 (1.3%)
Diarrhoea 2/300 (0.7%) 2/302 (0.7%)
Gastrointestinal Haemorrhage 3/300 (1%) 1/302 (0.3%)
Pancreatitis Acute 1/300 (0.3%) 3/302 (1%)
Gastritis 3/300 (1%) 0/302 (0%)
Intestinal Ischaemia 1/300 (0.3%) 2/302 (0.7%)
Constipation 2/300 (0.7%) 0/302 (0%)
Diverticulum Intestinal 2/300 (0.7%) 0/302 (0%)
Haemorrhoids 0/300 (0%) 2/302 (0.7%)
Ileus 1/300 (0.3%) 1/302 (0.3%)
Inguinal Hernia 2/300 (0.7%) 0/302 (0%)
Abdominal Haematoma 1/300 (0.3%) 0/302 (0%)
Abdominal Hernia 1/300 (0.3%) 0/302 (0%)
Abdominal Symptom 1/300 (0.3%) 0/302 (0%)
Colitis 1/300 (0.3%) 0/302 (0%)
Colitis Ulcerative 0/300 (0%) 1/302 (0.3%)
Colonic Polyp 1/300 (0.3%) 0/302 (0%)
Diverticular Perforation 0/300 (0%) 1/302 (0.3%)
Duodenal Ulcer 1/300 (0.3%) 0/302 (0%)
Duodenitis Haemorrhagic 1/300 (0.3%) 0/302 (0%)
Dyspepsia 1/300 (0.3%) 0/302 (0%)
Enteritis 1/300 (0.3%) 0/302 (0%)
Erosive Duodenitis 1/300 (0.3%) 0/302 (0%)
Gastric Haemorrhage 0/300 (0%) 1/302 (0.3%)
Gastric Ulcer 0/300 (0%) 1/302 (0.3%)
Haematemesis 1/300 (0.3%) 0/302 (0%)
Haematochezia 1/300 (0.3%) 0/302 (0%)
Ileus Paralytic 0/300 (0%) 1/302 (0.3%)
Intestinal Obstruction 1/300 (0.3%) 0/302 (0%)
Nausea 1/300 (0.3%) 0/302 (0%)
Oesophagitis 0/300 (0%) 1/302 (0.3%)
Pancreatitis Chronic 0/300 (0%) 1/302 (0.3%)
Peptic Ulcer 0/300 (0%) 1/302 (0.3%)
Reflux Oesophagitis 1/300 (0.3%) 0/302 (0%)
General disorders
Pyrexia 3/300 (1%) 4/302 (1.3%)
Sudden Death 4/300 (1.3%) 2/302 (0.7%)
Oedema Peripheral 3/300 (1%) 1/302 (0.3%)
Chest Pain 3/300 (1%) 0/302 (0%)
Asthenia 1/300 (0.3%) 1/302 (0.3%)
Catheter Related Complication 1/300 (0.3%) 1/302 (0.3%)
General Physical Health Deterioration 0/300 (0%) 2/302 (0.7%)
Oedema 1/300 (0.3%) 1/302 (0.3%)
Adverse Drug Reaction 0/300 (0%) 1/302 (0.3%)
Catheter Site Inflammation 1/300 (0.3%) 0/302 (0%)
Chills 1/300 (0.3%) 0/302 (0%)
Fatigue 0/300 (0%) 1/302 (0.3%)
Heparin-Induced Thrombocytopenia 1/300 (0.3%) 0/302 (0%)
Injection Site Thrombosis 1/300 (0.3%) 0/302 (0%)
Hepatobiliary disorders
Cholecystitis Acute 2/300 (0.7%) 3/302 (1%)
Cholelithiasis 1/300 (0.3%) 2/302 (0.7%)
Cholecystitis 0/300 (0%) 2/302 (0.7%)
Cholestasis Of Pregnancy 1/300 (0.3%) 0/302 (0%)
Hepatic Cyst 1/300 (0.3%) 0/302 (0%)
Hyperbilirubinaemia 0/300 (0%) 1/302 (0.3%)
Jaundice 0/300 (0%) 1/302 (0.3%)
Immune system disorders
Amyloidosis 1/300 (0.3%) 0/302 (0%)
Kidney Transplant Rejection 1/300 (0.3%) 0/302 (0%)
Infections and infestations
Pneumonia 9/300 (3%) 9/302 (3%)
Urinary Tract Infection 4/300 (1.3%) 8/302 (2.6%)
Sepsis 6/300 (2%) 3/302 (1%)
Gastroenteritis 2/300 (0.7%) 4/302 (1.3%)
Renal Cyst Infection 1/300 (0.3%) 4/302 (1.3%)
Appendicitis 2/300 (0.7%) 2/302 (0.7%)
Upper Respiratory Tract Infection 2/300 (0.7%) 2/302 (0.7%)
Erysipelas 2/300 (0.7%) 1/302 (0.3%)
Respiratory Tract Infection 1/300 (0.3%) 2/302 (0.7%)
Abscess Limb 0/300 (0%) 2/302 (0.7%)
Bacteraemia 2/300 (0.7%) 0/302 (0%)
Bronchopneumonia 1/300 (0.3%) 1/302 (0.3%)
Catheter Related Infection 2/300 (0.7%) 0/302 (0%)
Catheter Site Infection 1/300 (0.3%) 1/302 (0.3%)
Diverticulitis 1/300 (0.3%) 1/302 (0.3%)
Herpes Zoster 1/300 (0.3%) 1/302 (0.3%)
Pyelonephritis 2/300 (0.7%) 0/302 (0%)
Pyelonephritis Acute 1/300 (0.3%) 1/302 (0.3%)
Sepsis Syndrome 2/300 (0.7%) 0/302 (0%)
Bronchitis Acute 0/300 (0%) 1/302 (0.3%)
Catheter Sepsis 0/300 (0%) 1/302 (0.3%)
Cellulitis 0/300 (0%) 1/302 (0.3%)
Cholecystitis Infective 1/300 (0.3%) 0/302 (0%)
Clostridial Infection 1/300 (0.3%) 0/302 (0%)
Epidemic Nephropathy 0/300 (0%) 1/302 (0.3%)
Escherichia Sepsis 1/300 (0.3%) 0/302 (0%)
Fungal Peritonitis 0/300 (0%) 1/302 (0.3%)
Hepatic Cyst Infection 1/300 (0.3%) 0/302 (0%)
Hepatitis C 1/300 (0.3%) 0/302 (0%)
Infected Skin Ulcer 0/300 (0%) 1/302 (0.3%)
Infection 1/300 (0.3%) 0/302 (0%)
Kidney Infection 1/300 (0.3%) 0/302 (0%)
Localised Infection 0/300 (0%) 2/302 (0.7%)
Lower Respiratory Tract Infection 1/300 (0.3%) 0/302 (0%)
Lung Infection 0/300 (0%) 1/302 (0.3%)
Pneumonia Fungal 1/300 (0.3%) 0/302 (0%)
Sialoadenitis 1/300 (0.3%) 0/302 (0%)
Staphylococcal Sepsis 0/300 (0%) 1/302 (0.3%)
Streptococcal Sepsis 1/300 (0.3%) 0/302 (0%)
Urosepsis 1/300 (0.3%) 0/302 (0%)
Wound Infection 0/300 (0%) 1/302 (0.3%)
Injury, poisoning and procedural complications
Arteriovenous Fistula Thrombosis 0/300 (0%) 4/302 (1.3%)
Hip Fracture 1/300 (0.3%) 3/302 (1%)
Arteriovenous Fistula Site Complication 3/300 (1%) 0/302 (0%)
Complications Of Transplanted Kidney 1/300 (0.3%) 1/302 (0.3%)
Femoral Neck Fracture 2/300 (0.7%) 0/302 (0%)
Head Injury 1/300 (0.3%) 1/302 (0.3%)
Humerus Fracture 1/300 (0.3%) 1/302 (0.3%)
Acetabulum Fracture 0/300 (0%) 1/302 (0.3%)
Arterial Injury 1/300 (0.3%) 0/302 (0%)
Arteriovenous Fistula Site Haemorrhage 1/300 (0.3%) 0/302 (0%)
Cardiac Pacemaker Malfunction 0/300 (0%) 1/302 (0.3%)
Concussion 0/300 (0%) 1/302 (0.3%)
Eye Injury 1/300 (0.3%) 0/302 (0%)
Femur Fracture 0/300 (0%) 1/302 (0.3%)
Injury 1/300 (0.3%) 0/302 (0%)
Joint Injury 1/300 (0.3%) 0/302 (0%)
Medical Device Complication 1/300 (0.3%) 0/302 (0%)
Medication Error 1/300 (0.3%) 0/302 (0%)
Multiple Fractures 0/300 (0%) 1/302 (0.3%)
Open Wound 1/300 (0.3%) 0/302 (0%)
Post Procedural Haematoma 1/300 (0.3%) 0/302 (0%)
Post Procedural Haemorrhage 1/300 (0.3%) 0/302 (0%)
Postoperative Hernia 0/300 (0%) 1/302 (0.3%)
Procedural Complication 1/300 (0.3%) 0/302 (0%)
Renal Haematoma 1/300 (0.3%) 0/302 (0%)
Shunt Thrombosis 1/300 (0.3%) 0/302 (0%)
Subdural Haematoma 1/300 (0.3%) 0/302 (0%)
Subdural Haemorrhage 1/300 (0.3%) 0/302 (0%)
Vascular Access Complication 0/300 (0%) 1/302 (0.3%)
Investigations
Blood Pressure Increased 3/300 (1%) 0/302 (0%)
Biopsy Liver 1/300 (0.3%) 0/302 (0%)
Blood Creatine Phosphokinase Increased 0/300 (0%) 1/302 (0.3%)
Transaminases Increased 0/300 (0%) 1/302 (0.3%)
Urine Cytology Abnormal 1/300 (0.3%) 0/302 (0%)
Weight Decreased 1/300 (0.3%) 0/302 (0%)
Weight Increased 0/300 (0%) 1/302 (0.3%)
Metabolism and nutrition disorders
Hypoglycaemia 6/300 (2%) 1/302 (0.3%)
Hyperkalaemia 3/300 (1%) 1/302 (0.3%)
Dehydration 1/300 (0.3%) 2/302 (0.7%)
Diabetes Mellitus Inadequate Control 2/300 (0.7%) 1/302 (0.3%)
Fluid Overload 3/300 (1%) 0/302 (0%)
Fluid Retention 2/300 (0.7%) 1/302 (0.3%)
Hyperglycaemia 0/300 (0%) 3/302 (1%)
Metabolic Acidosis 2/300 (0.7%) 1/302 (0.3%)
Diabetes Mellitus 1/300 (0.3%) 1/302 (0.3%)
Diabetic Foot 0/300 (0%) 1/302 (0.3%)
Diabetic Ketoacidosis 1/300 (0.3%) 0/302 (0%)
Electrolyte Imbalance 0/300 (0%) 1/302 (0.3%)
Gout 1/300 (0.3%) 0/302 (0%)
Hyponatraemia 1/300 (0.3%) 0/302 (0%)
Musculoskeletal and connective tissue disorders
Back Pain 4/300 (1.3%) 0/302 (0%)
Localised Osteoarthritis 2/300 (0.7%) 1/302 (0.3%)
Myalgia 2/300 (0.7%) 0/302 (0%)
Pain In Extremity 0/300 (0%) 2/302 (0.7%)
Arthralgia 0/300 (0%) 1/302 (0.3%)
Arthritis 1/300 (0.3%) 0/302 (0%)
Gouty Arthritis 0/300 (0%) 1/302 (0.3%)
Joint Swelling 1/300 (0.3%) 0/302 (0%)
Muscular Weakness 0/300 (0%) 1/302 (0.3%)
Musculoskeletal Chest Pain 0/300 (0%) 1/302 (0.3%)
Myopathy 1/300 (0.3%) 0/302 (0%)
Osteoarthritis 0/300 (0%) 1/302 (0.3%)
Osteoarthropathy 0/300 (0%) 1/302 (0.3%)
Rhabdomyolysis 1/300 (0.3%) 0/302 (0%)
Tendonitis 0/300 (0%) 1/302 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder Cancer 2/300 (0.7%) 1/302 (0.3%)
Prostate Cancer 1/300 (0.3%) 2/302 (0.7%)
Renal Cell Carcinoma Stage Unspecified 1/300 (0.3%) 2/302 (0.7%)
Colon Cancer 0/300 (0%) 2/302 (0.7%)
Lung Neoplasm Malignant 1/300 (0.3%) 1/302 (0.3%)
Bladder Neoplasm 1/300 (0.3%) 0/302 (0%)
Breast Cancer 0/300 (0%) 1/302 (0.3%)
Breast Neoplasm 0/300 (0%) 1/302 (0.3%)
Cervix Carcinoma 1/300 (0.3%) 0/302 (0%)
Colon Adenoma 1/300 (0.3%) 0/302 (0%)
Colon Cancer Metastatic 0/300 (0%) 1/302 (0.3%)
Gallbladder Cancer 1/300 (0.3%) 0/302 (0%)
Gammopathy 0/300 (0%) 1/302 (0.3%)
Gastric Cancer 1/300 (0.3%) 0/302 (0%)
Laryngeal Cancer 1/300 (0.3%) 0/302 (0%)
Malignant Melanoma 1/300 (0.3%) 0/302 (0%)
Metastases To Liver 1/300 (0.3%) 0/302 (0%)
Metastatic Neoplasm 1/300 (0.3%) 0/302 (0%)
Ovarian Adenoma 0/300 (0%) 1/302 (0.3%)
Pancreatic Neoplasm 0/300 (0%) 1/302 (0.3%)
Parathyroid Tumour 0/300 (0%) 1/302 (0.3%)
Prostatic Adenoma 0/300 (0%) 1/302 (0.3%)
Tongue Neoplasm Malignant Stage Unspecified 0/300 (0%) 1/302 (0.3%)
Nervous system disorders
Cerebrovascular Accident 7/300 (2.3%) 5/302 (1.7%)
Syncope 1/300 (0.3%) 3/302 (1%)
Headache 2/300 (0.7%) 1/302 (0.3%)
Diabetic Neuropathy 2/300 (0.7%) 0/302 (0%)
Dizziness 1/300 (0.3%) 1/302 (0.3%)
Transient Ischaemic Attack 2/300 (0.7%) 0/302 (0%)
Carotid Artery Stenosis 0/300 (0%) 1/302 (0.3%)
Carpal Tunnel Syndrome 1/300 (0.3%) 0/302 (0%)
Cervical Root Pain 0/300 (0%) 1/302 (0.3%)
Cervicobrachial Syndrome 0/300 (0%) 1/302 (0.3%)
Dementia Alzheimer's Type 0/300 (0%) 1/302 (0.3%)
Diabetic Hyperglycaemic Coma 1/300 (0.3%) 0/302 (0%)
Disturbance In Attention 1/300 (0.3%) 0/302 (0%)
Dizziness Postural 0/300 (0%) 1/302 (0.3%)
Hypersomnia 1/300 (0.3%) 0/302 (0%)
Hypertonia 1/300 (0.3%) 0/302 (0%)
Loss Of Consciousness 0/300 (0%) 1/302 (0.3%)
Neuralgia 0/300 (0%) 1/302 (0.3%)
Uraemic Encephalopathy 1/300 (0.3%) 0/302 (0%)
Pregnancy, puerperium and perinatal conditions
Pregnancy 2/300 (0.7%) 1/302 (0.3%)
Premature Labour 1/300 (0.3%) 0/302 (0%)
Psychiatric disorders
Confusional State 2/300 (0.7%) 0/302 (0%)
Amnestic Disorder 1/300 (0.3%) 0/302 (0%)
Disorientation 1/300 (0.3%) 0/302 (0%)
Renal and urinary disorders
Renal Failure 17/300 (5.7%) 12/302 (4%)
Renal Impairment 5/300 (1.7%) 9/302 (3%)
Renal Failure Chronic 7/300 (2.3%) 6/302 (2%)
Azotaemia 5/300 (1.7%) 1/302 (0.3%)
Haematuria 4/300 (1.3%) 1/302 (0.3%)
Urinary Retention 1/300 (0.3%) 3/302 (1%)
Hydronephrosis 0/300 (0%) 2/302 (0.7%)
Renal Cyst Ruptured 1/300 (0.3%) 1/302 (0.3%)
Renal Failure Acute 1/300 (0.3%) 1/302 (0.3%)
Renal Haemorrhage 1/300 (0.3%) 1/302 (0.3%)
Calculus Ureteric 1/300 (0.3%) 0/302 (0%)
Glomerulonephritis 0/300 (0%) 1/302 (0.3%)
Haemorrhage Urinary Tract 1/300 (0.3%) 0/302 (0%)
Hypertensive Nephropathy 0/300 (0%) 1/302 (0.3%)
Nephritis Interstitial 1/300 (0.3%) 0/302 (0%)
Nephrolithiasis 0/300 (0%) 1/302 (0.3%)
Renal Artery Stenosis 0/300 (0%) 1/302 (0.3%)
Urinary Bladder Polyp 1/300 (0.3%) 0/302 (0%)
Reproductive system and breast disorders
Benign Prostatic Hyperplasia 1/300 (0.3%) 0/302 (0%)
Epididymitis 1/300 (0.3%) 0/302 (0%)
Ovarian Cyst 0/300 (0%) 1/302 (0.3%)
Prostatitis 1/300 (0.3%) 0/302 (0%)
Uterine Prolapse 0/300 (0%) 1/302 (0.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea 2/300 (0.7%) 3/302 (1%)
Pulmonary Embolism 3/300 (1%) 1/302 (0.3%)
Pleural Effusion 1/300 (0.3%) 2/302 (0.7%)
Respiratory Failure 1/300 (0.3%) 2/302 (0.7%)
Lung Disorder 2/300 (0.7%) 0/302 (0%)
Chronic Obstructive Airways Disease 1/300 (0.3%) 0/302 (0%)
Epistaxis 1/300 (0.3%) 0/302 (0%)
Haemoptysis 1/300 (0.3%) 0/302 (0%)
Hypercapnia 0/300 (0%) 1/302 (0.3%)
Laryngeal Dysplasia 1/300 (0.3%) 0/302 (0%)
Vocal Cord Polyp 1/300 (0.3%) 0/302 (0%)
Pulmonary Oedema 0/300 (0%) 1/302 (0.3%)
Skin and subcutaneous tissue disorders
Skin Ulcer 0/300 (0%) 3/302 (1%)
Angioneurotic Oedema 1/300 (0.3%) 0/302 (0%)
Urticaria 1/300 (0.3%) 0/302 (0%)
Surgical and medical procedures
Nephrectomy 2/300 (0.7%) 1/302 (0.3%)
Insertion Of Ambulatory Peritoneal Catheter 1/300 (0.3%) 1/302 (0.3%)
Arteriovenous Fistula Operation 0/300 (0%) 1/302 (0.3%)
Cataract Operation 0/300 (0%) 1/302 (0.3%)
Catheter Placement 1/300 (0.3%) 0/302 (0%)
Eye Operation 1/300 (0.3%) 0/302 (0%)
Knee Arthroplasty 1/300 (0.3%) 0/302 (0%)
Peritoneal Dialysis 1/300 (0.3%) 0/302 (0%)
Rehabilitation Therapy 1/300 (0.3%) 0/302 (0%)
Renal Transplant 1/300 (0.3%) 0/302 (0%)
Vascular disorders
Peripheral Vascular Disorder 12/300 (4%) 7/302 (2.3%)
Hypotension 2/300 (0.7%) 2/302 (0.7%)
Deep Vein Thrombosis 1/300 (0.3%) 2/302 (0.7%)
Arterial Stenosis 2/300 (0.7%) 0/302 (0%)
Hypertension 0/300 (0%) 2/302 (0.7%)
Hypertensive Crisis 2/300 (0.7%) 0/302 (0%)
Lymphocele 1/300 (0.3%) 1/302 (0.3%)
Phlebitis 2/300 (0.7%) 0/302 (0%)
Aneurysm Arteriovenous 1/300 (0.3%) 0/302 (0%)
Aortic Aneurysm 1/300 (0.3%) 0/302 (0%)
Arteriosclerosis 0/300 (0%) 1/302 (0.3%)
Arteriovenous Fistula, Acquired 0/300 (0%) 1/302 (0.3%)
Circulatory Collapse 1/300 (0.3%) 0/302 (0%)
Malignant Hypertension 1/300 (0.3%) 0/302 (0%)
Orthostatic Hypotension 1/300 (0.3%) 0/302 (0%)
Subclavian Artery Aneurysm 1/300 (0.3%) 0/302 (0%)
Thrombophlebitis 1/300 (0.3%) 0/302 (0%)
Venous Thrombosis Limb 0/300 (0%) 1/302 (0.3%)
Other (Not Including Serious) Adverse Events
Early Epoetin Beta Therapy Late Epoetin Beta Therapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 243/300 (81%) 228/302 (75.5%)
Gastrointestinal disorders
Diarrhoea 24/300 (8%) 25/302 (8.3%)
Constipation 22/300 (7.3%) 19/302 (6.3%)
Nausea 15/300 (5%) 14/302 (4.6%)
Vomiting 15/300 (5%) 12/302 (4%)
General disorders
Oedema Peripheral 20/300 (6.7%) 11/302 (3.6%)
Asthenia 16/300 (5.3%) 17/302 (5.6%)
Fatigue 14/300 (4.7%) 17/302 (5.6%)
Infections and infestations
Upper respiratory tract infection 16/300 (5.3%) 28/302 (9.3%)
Urinary tract infection 26/300 (8.7%) 29/302 (9.6%)
Nasopharyngitis 24/300 (8%) 23/302 (7.6%)
Influenza 26/300 (8.7%) 12/302 (4%)
Bronchitis 12/300 (4%) 16/302 (5.3%)
Bronchitis Acute 15/300 (5%) 6/302 (2%)
Investigations
Blood Pressure Increased 19/300 (6.3%) 13/302 (4.3%)
Metabolism and nutrition disorders
Hyperkalaemia 28/300 (9.3%) 30/302 (9.9%)
Hyperphosphataemia 27/300 (9%) 22/302 (7.3%)
Gout 15/300 (5%) 16/302 (5.3%)
Musculoskeletal and connective tissue disorders
Back pain 22/300 (7.3%) 33/302 (10.9%)
Arthralgia 21/300 (7%) 19/302 (6.3%)
Pain in extremity 18/300 (6%) 16/302 (5.3%)
Muscle cramp 9/300 (3%) 16/302 (5.3%)
Nervous system disorders
Headache 30/300 (10%) 15/302 (5%)
Dizziness 18/300 (6%) 13/302 (4.3%)
Psychiatric disorders
Insomnia 12/300 (4%) 23/302 (7.6%)
Renal and urinary disorders
Renal Failure 93/300 (31%) 87/302 (28.8%)
Renal Failure Chronic 33/300 (11%) 46/302 (15.2%)
Renal Impairment 27/300 (9%) 23/302 (7.6%)
Respiratory, thoracic and mediastinal disorders
Cough 20/300 (6.7%) 16/302 (5.3%)
Skin and subcutaneous tissue disorders
Pruritis 27/300 (9%) 18/302 (6%)
Vascular disorders
Hypertension 89/300 (29.7%) 58/302 (19.2%)
Hypotension 13/300 (4.3%) 16/302 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.

Results Point of Contact

Name/Title Roche Trial Information Hotline
Organization F. Hoffmann-La Roche AG
Phone +41 61 6878333
Email global.trial_information@roche.com
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00321919
Other Study ID Numbers:
  • BA16169
First Posted:
May 4, 2006
Last Update Posted:
Jun 29, 2016
Last Verified:
May 1, 2016