Evaluation of Two Epoetin Alfa Dosing Strategies in Subje... | NCT02253654

Label	Type	Description	Intervention Names
Epoetin alfa Alternative Titration	Experimental	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for up to 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose changes may have occurred every 2 weeks according to the alternative dosing algorithm, where smaller, frequent dose adjustments were permitted based on six hemoglobin categories.	Drug: Epoetin alfa
Epoetin alfa USPI Titration	Active Comparator	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose decreases were permitted every 2 weeks and beginning at week 5 dose increases could only occur ≥ 4 weeks from the last dose increase, according to the United States package insert (USPI) dosing algorithm which includes four categories of hemoglobin levels.	Drug: Epoetin alfa

Name	Type	Description	Arm Group Labels	Other Names
Epoetin alfa	Drug	Administered intravenously (IV) three times a week (TIW) by appropriately trained healthcare professionals during hemodialysis.	Epoetin alfa Alternative Titration

Measure	Description	Time Frame
Percentage of Hemoglobin Measurements Within 10 to 11 g/dL During the Evaluation Period	Hemoglobin was measured every 2 weeks during the evaluation period. The percentage of these measurements that were within the range of 10-11 g/dL was calculated for each participant.	The evaluation period (weeks 13-37)

Measure	Description	Time Frame
Hemoglobin Concentration at Each Visit		Baseline (screening visit) and weeks 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37
Percentage of Participants With Transfusion Events Overall and During Each Study Period	The percentage of participants who received red blood cell (RBC) transfusions during the study and during each study period.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Informed consent obtained prior to initiation of any study-specific activities/procedures
Age 18 or older
Prescribed hemodialysis three times a week (TIW) for ≥ 12 weeks prior to randomization
Prescribed IV administration of epoetin alfa TIW for ≥ 12 weeks prior to randomization
Prescribed ≥ 3000 Units/week (ie, ≥ 1000 Units/administration) and < 90,000 Units/week (ie, < 30,000 Units/administration) of epoetin alfa during the 4 weeks prior to randomization
Received ≥ 4 doses of epoetin alfa during the 2 weeks prior to randomization
Hemoglobin concentration ≤ 11.0 g/dL, per the most recent local laboratory value obtained during the 2 weeks prior to randomization
Hemoglobin concentration ≤ 11.0 g/dL, at the screening visit, using the hemoglobin point of care device provided by Amgen
Iron replete, defined as a transferrin saturation (TSAT) ≥ 20% and a ferritin ≥ 100 ng/mL, per the most recent local laboratory value obtained during the 4 weeks prior to randomization

Exclusion Criteria:

Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s) prior to randomization
Other investigational procedures while participating in this study are excluded
Systemic hematologic disease (eg, sickle cell anemia, myelodysplastic syndrome, hematologic malignancy)
Current or prior malignancy within 5 years of randomization, with the exception of non-melanoma skin cancers, cervical or breast ductal carcinoma in situ
Treatment for any malignancy (eg, radiation, chemotherapy, hormone therapy or biologics) within 5 years of randomization, with the exception of locally excised non-melanoma skin cancers, cervical or breast ductal carcinoma in situ
Subject is currently pregnant or planning to become pregnant during treatment and for 30 days after the end of treatment
Subject is currently breast feeding or planning on breast feeding during treatment and for 30 days after the end of treatment
Females of reproductive potential who are not willing to use an acceptable method of effective contraception during treatment and for at least 30 days after the end of treatment
Currently receiving IV antibiotics
Currently receiving systemic immunosuppressive therapy known to cause anemia, including treatment for active hepatitis (eg, azathioprine, mycophenolate mofetil, ≥ 10 mg prednisone [or equivalent]/day, interferon)
Known human immunodeficiency virus (HIV) positive
Known neutralizing anti-erythropoietic protein antibodies
Known sensitivity to epoetin alfa
Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, planned vacations where away from dialysis unit for more than 2 weeks) to the best of the subject and investigator's knowledge
History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
Previously entered this study
Occurrence of any of the following within 8 weeks prior to randomization:
- Seizure
- Clinically relevant active bleeding (eg, gastrointestinal bleed)
- RBC transfusion
- Any hospitalization or observational stay > 24 hours
Uncontrolled hypertension, per the investigator within the 4 weeks prior to randomization
Expected or scheduled solid organ transplant(eg, kidney) within 40 weeks after randomization
Expected or scheduled to change dialysis modality (eg, peritoneal dialysis, home hemodialysis) within 40 weeks after randomization

Name	Affiliation	Role
MD	Amgen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Cerritos	California	90703	United States
Research Site

Label	URL
AmgenTrials clinical trials website	View source

ID	Title	Description
FG000	Epoetin Alfa Alternative Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for up to 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose changes may have occurred every 2 weeks according to the alternative dosing algorithm, where smaller, frequent dose adjustments were permitted based on six hemoglobin categories.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Hemoglobin Measurements Within 10 to 11 g/dL During the Evaluation Period

Hemoglobin was measured every 2 weeks during the evaluation period. The percentage of these measurements that were within the range of 10-11 g/dL was calculated for each participant.

The Primary Analysis Set which consists of all randomized participants who had at least 6 hemoglobin measurements during the evaluation period while on study and receiving investigational product.

Posted

Mean

Standard Deviation

percentage of hemoglobin measurements

The evaluation period (weeks 13-37)

ID	Title	Description
OG000	Epoetin Alfa Alternative Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for up to 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose changes may have occurred every 2 weeks according to the alternative dosing algorithm, where smaller, frequent dose adjustments were permitted based on six hemoglobin categories.
OG001	Epoetin Alfa USPI Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose decreases were permitted every 2 weeks and beginning at week 5 dose increases could only occur ≥ 4 weeks from the last dose increase, according to the United States package insert (USPI) dosing algorithm which includes four categories of hemoglobin levels.

Units	Counts
Participants	OG00089 OG001100

Title

Denominators

Categories

Title	Measurements
	OG00046.41± 2.39 OG00146.02± 2.56

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The difference between treatment groups for the percent of hemoglobin measurements within 10.0 to 11.0 g/dL during the evaluation period was tested using a 1-sided t-test with a significance level of 0.025.	t-test, 1 sided		0.46		Treatment difference	0.39	Standard Error of the Mean	3.53	1-Sided	97.5	-6.58						Superiority or Other

Secondary

Hemoglobin Concentration at Each Visit

Primary analysis set with available data at each time point

Posted

Mean

Standard Deviation

g/dL

Baseline (screening visit) and weeks 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37

ID	Title	Description
OG000	Epoetin Alfa Alternative Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for up to 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose changes may have occurred every 2 weeks according to the alternative dosing algorithm, where smaller, frequent dose adjustments were permitted based on six hemoglobin categories.
OG001	Epoetin Alfa USPI Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose decreases were permitted every 2 weeks and beginning at week 5 dose increases could only occur ≥ 4 weeks from the last dose increase, according to the United States package insert (USPI) dosing algorithm which includes four categories of hemoglobin levels.

Secondary

Percentage of Participants With Transfusion Events Overall and During Each Study Period

The percentage of participants who received red blood cell (RBC) transfusions during the study and during each study period.

Primary analysis set with available data in each study period

Posted

Number

percentage of participants

Overall Study: Study week 1 to week 41; Titration Period: Study week 1 to week 12; Evaluation Period: Study week 13 to week 37; Safety Follow-up Period: Study week 38 to week 41

ID	Title	Description
OG000	Epoetin Alfa Alternative Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for up to 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose changes may have occurred every 2 weeks according to the alternative dosing algorithm, where smaller, frequent dose adjustments were permitted based on six hemoglobin categories.
OG001	Epoetin Alfa USPI Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose decreases were permitted every 2 weeks and beginning at week 5 dose increases could only occur ≥ 4 weeks from the last dose increase, according to the United States package insert (USPI) dosing algorithm which includes four categories of hemoglobin levels.

Secondary

Hemoglobin Rate of Change at Each Visit

Hemoglobin rate of change (ROC) was calculated for each visit using the following formula: ROC = (current visit hemoglobin value - previous visit hemoglobin value) / number of days between each visit * 14. A positive value indicates a rate of rise and a negative value indicates a rate of decline.

Primary analysis set with available data at each time point

Posted

Mean

Standard Deviation

g/dL/2 weeks

Baseline (screening visit) and weeks 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37

ID	Title	Description
OG000	Epoetin Alfa Alternative Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for up to 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose changes may have occurred every 2 weeks according to the alternative dosing algorithm, where smaller, frequent dose adjustments were permitted based on six hemoglobin categories.
OG001	Epoetin Alfa USPI Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose decreases were permitted every 2 weeks and beginning at week 5 dose increases could only occur ≥ 4 weeks from the last dose increase, according to the United States package insert (USPI) dosing algorithm which includes four categories of hemoglobin levels.

Secondary

Hemoglobin Intra-subject Variability

Intra-subject variability was defined for each participant as the standard deviation (SD) of all of the hemoglobin concentrations during the evaluation period for the participant. The mean intra-subject SD for all participants is the sum of the intra-subject SDs divided by the total number of participants evaluated.

Primary analysis set

Posted

Mean

Standard Deviation

g/dL

The evaluation period (weeks 13 to 37)

ID	Title	Description
OG000	Epoetin Alfa Alternative Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for up to 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose changes may have occurred every 2 weeks according to the alternative dosing algorithm, where smaller, frequent dose adjustments were permitted based on six hemoglobin categories.
OG001	Epoetin Alfa USPI Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose decreases were permitted every 2 weeks and beginning at week 5 dose increases could only occur ≥ 4 weeks from the last dose increase, according to the United States package insert (USPI) dosing algorithm which includes four categories of hemoglobin levels.

Secondary

Percentage of Participants With Hemoglobin Excursions at Each Visit

An excursion is identified as an event when a hemoglobin concentration fell below or exceeded the pre-specified thresholds of: - < 9.0 g/dL, or - > 11.0 g/dL, or - > 12.0 g/dL. The percentage of participants with any excursions and excursions in each subcategory at each time point and overall during the study are reported.

Primary analysis set with available data at each time point

Posted

Number

percentage of participants

Baseline (screening visit) and weeks 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, and 37

ID	Title	Description
OG000	Epoetin Alfa Alternative Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for up to 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose changes may have occurred every 2 weeks according to the alternative dosing algorithm, where smaller, frequent dose adjustments were permitted based on six hemoglobin categories.
OG001	Epoetin Alfa USPI Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose decreases were permitted every 2 weeks and beginning at week 5 dose increases could only occur ≥ 4 weeks from the last dose increase, according to the United States package insert (USPI) dosing algorithm which includes four categories of hemoglobin levels.

Secondary

Weekly Epoetin Alfa Dose at Each Visit

Primary analysis set with available data at each time point

Posted

Mean

Standard Deviation

units

Weeks 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35

ID	Title	Description
OG000	Epoetin Alfa Alternative Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for up to 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose changes may have occurred every 2 weeks according to the alternative dosing algorithm, where smaller, frequent dose adjustments were permitted based on six hemoglobin categories.
OG001	Epoetin Alfa USPI Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose decreases were permitted every 2 weeks and beginning at week 5 dose increases could only occur ≥ 4 weeks from the last dose increase, according to the United States package insert (USPI) dosing algorithm which includes four categories of hemoglobin levels.

Units	Counts

Secondary

Number of RBC Units Transfused Overall and During Each Study Period

The number of red blood cell (RBC) units transfused during the study and during each study period.

Primary analysis set with available data in each study period

Posted

Number

participants

Overall Study: Study week 1 to week 41; Titration Period: Study week 1 to week 12; Evaluation Period: Study week 13 to week 37; Safety Follow-up Period: Study week 38 to week 41

ID	Title	Description
OG000	Epoetin Alfa Alternative Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for up to 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose changes may have occurred every 2 weeks according to the alternative dosing algorithm, where smaller, frequent dose adjustments were permitted based on six hemoglobin categories.
OG001	Epoetin Alfa USPI Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose decreases were permitted every 2 weeks and beginning at week 5 dose increases could only occur ≥ 4 weeks from the last dose increase, according to the United States package insert (USPI) dosing algorithm which includes four categories of hemoglobin levels.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Immune thrombocytopenic purpura	Blood and lymphatic system disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0011 affected107 at risk
Angina pectoris	Cardiac disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0012 affected107 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0012 affected107 at risk
Cardiac arrest	Cardiac disorders	MedDRA 19	Systematic Assessment	EG0003 affected104 at risk EG0011 affected107 at risk
Cardiac failure	Cardiac disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Cardiac failure acute	Cardiac disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 19	Systematic Assessment	EG0003 affected104 at risk EG0012 affected107 at risk
Cardiac valve disease	Cardiac disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Coronary artery disease	Cardiac disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0012 affected107 at risk
Myocardial infarction	Cardiac disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0011 affected107 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Hyperparathyroidism secondary	Endocrine disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Colitis	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Constipation	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Diabetic gastroparesis	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Diverticulum	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Gastritis erosive	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0002 affected104 at risk EG0013 affected107 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Vomiting	Gastrointestinal disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Asthenia	General disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0011 affected107 at risk
Catheter site haemorrhage	General disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Chest pain	General disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Death	General disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Non-cardiac chest pain	General disorders	MedDRA 19	Systematic Assessment	EG0002 affected104 at risk EG0010 affected107 at risk
Pyrexia	General disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Vascular stent restenosis	General disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 19	Systematic Assessment	EG0002 affected104 at risk EG0010 affected107 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Haemorrhagic hepatic cyst	Hepatobiliary disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Abscess limb	Infections and infestations	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Arthritis bacterial	Infections and infestations	MedDRA 19	Systematic Assessment	EG0002 affected104 at risk EG0010 affected107 at risk
Atypical pneumonia	Infections and infestations	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Bronchitis	Infections and infestations	MedDRA 19	Systematic Assessment	EG0002 affected104 at risk EG0010 affected107 at risk
Cellulitis	Infections and infestations	MedDRA 19	Systematic Assessment	EG0002 affected104 at risk EG0010 affected107 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Cystitis escherichia	Infections and infestations	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Device related infection	Infections and infestations	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Endocarditis	Infections and infestations	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Gastroenteritis	Infections and infestations	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0011 affected107 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Hepatitis C	Infections and infestations	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Herpes zoster	Infections and infestations	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Infected skin ulcer	Infections and infestations	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Pneumonia	Infections and infestations	MedDRA 19	Systematic Assessment	EG0002 affected104 at risk EG0016 affected107 at risk
Scrotal abscess	Infections and infestations	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Sepsis	Infections and infestations	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0011 affected107 at risk
Sepsis syndrome	Infections and infestations	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Staphylococcal bacteraemia	Infections and infestations	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Staphylococcal sepsis	Infections and infestations	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Arteriovenous fistula occlusion	Injury, poisoning and procedural complications	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Arteriovenous fistula site haemorrhage	Injury, poisoning and procedural complications	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0012 affected107 at risk
Arteriovenous fistula thrombosis	Injury, poisoning and procedural complications	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Graft haemorrhage	Injury, poisoning and procedural complications	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Thoracic vertebral fracture	Injury, poisoning and procedural complications	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Diabetic complication	Metabolism and nutrition disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Fluid overload	Metabolism and nutrition disorders	MedDRA 19	Systematic Assessment	EG0003 affected104 at risk EG0019 affected107 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 19	Systematic Assessment	EG0003 affected104 at risk EG0011 affected107 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 19	Systematic Assessment	EG0002 affected104 at risk EG0010 affected107 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Bone disorder	Musculoskeletal and connective tissue disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Joint instability	Musculoskeletal and connective tissue disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Metastatic neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0014 affected107 at risk
Encephalopathy	Nervous system disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Hemiparesis	Nervous system disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Hemiplegia	Nervous system disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Delirium	Psychiatric disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Mental status changes	Psychiatric disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0012 affected107 at risk
End stage renal disease	Renal and urinary disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Bronchitis chronic	Respiratory, thoracic and mediastinal disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0012 affected107 at risk
Haemothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0011 affected107 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0013 affected107 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0011 affected107 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 19	Systematic Assessment	EG0002 affected104 at risk EG0010 affected107 at risk
Respiratory arrest	Respiratory, thoracic and mediastinal disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Arteriosclerosis	Vascular disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 19	Systematic Assessment	EG0002 affected104 at risk EG0010 affected107 at risk
Embolism	Vascular disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Hypertension	Vascular disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0012 affected107 at risk
Hypertensive crisis	Vascular disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0011 affected107 at risk
Hypotension	Vascular disorders	MedDRA 19	Systematic Assessment	EG0002 affected104 at risk EG0012 affected107 at risk
Peripheral vascular disorder	Vascular disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk
Steal syndrome	Vascular disorders	MedDRA 19	Systematic Assessment	EG0001 affected104 at risk EG0010 affected107 at risk
Superior vena cava syndrome	Vascular disorders	MedDRA 19	Systematic Assessment	EG0000 affected104 at risk EG0011 affected107 at risk

ID	Term
D051436	Renal Insufficiency, Chronic
D000740	Anemia

ID	Term
D051437	Renal Insufficiency
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases

ID	Term
D004921	Erythropoietin
D003115	Colony-Stimulating Factors
D006023	Glycoproteins
D006001	Glycoconjugates
D002241	Carbohydrates
D016298	Hematopoietic Cell Growth Factors
D016207	Cytokines
D036341	Intercellular Signaling Peptides and Proteins
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D011506	Proteins
D001685	Biological Factors

ID	Title	Description
BG000	Epoetin Alfa Alternative Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for up to 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose changes may have occurred every 2 weeks according to the alternative dosing algorithm, where smaller, frequent dose adjustments were permitted based on six hemoglobin categories.
BG001	Epoetin Alfa USPI Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose decreases were permitted every 2 weeks and beginning at week 5 dose increases could only occur ≥ 4 weeks from the last dose increase, according to the United States package insert (USPI) dosing algorithm which includes four categories of hemoglobin levels.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Epoetin Alfa Alternative Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for up to 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose changes may have occurred every 2 weeks according to the alternative dosing algorithm, where smaller, frequent dose adjustments were permitted based on six hemoglobin categories.			37	104	19	104
EG001	Epoetin Alfa USPI Titration	Participants received epoetin alfa administered intravenously three times a week during hemodialysis for 37 weeks. For the first two weeks the dose of epoetin alfa was based on the dose at the time of screening. Beginning at week 3 dose decreases were permitted every 2 weeks and beginning at week 5 dose increases could only occur ≥ 4 weeks from the last dose increase, according to the United States package insert (USPI) dosing algorithm which includes four categories of hemoglobin levels.			39	107	26	107