Darbepoetin Alfa and Anemia of Cancer

• Sponsor: Amgen (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00989092
• Collaborator: (none)
• Enrollment: 287
• Arms: 2
• Duration (Months): 25

Study Details

Study Description

Brief Summary

This phase 2, multicenter, randomized, open-label, comparative study was designed to determine the effect of darbepoetin alfa on hospital days, economic outcomes, and health related quality of life (HRQOL) in anemic patients with nonmyeloid malignancies who were not receiving chemotherapy. Participants were randomly assigned in a 4:1 allocation ratio to receive either 21 weeks of darbepoetin alfa treatment (treatment group) or 12 weeks of observation followed by up to 9 weeks of darbepoetin alfa treatment (observation group).

Condition or Disease	Intervention/Treatment	Phase
Anemia; Anemia of Cancer; Cancer; Carcinoma; Neoplasms; Non-Myeloid Malignancies	Biological: darbepoetin alfa	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 287 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A Randomized, Open-label, Comparative Study to Estimate the Effect of Darbepoetin Alfa on Hospital Days, Economic Outcomes, and Health-related Quality of Life in Subjects With Nonmyeloid Malignancies and Anemia of Cancer
• Study Start Date: May 1, 2002
• Actual Primary Completion Date: Jan 1, 2004
• Actual Study Completion Date: Jun 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Other: Observational Group Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered to the observation group during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participants hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.	Biological: darbepoetin alfa; Administered subcutaneously.; Other Names: Aranesp®
Active Comparator: 21 week treatment group Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at week 7 (to 5.0 μg/kg once every 2 weeks) or at week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at week 7.	Biological: darbepoetin alfa; Administered subcutaneously.; Other Names: Aranesp®

Outcome Measures

Primary Outcome Measures

1. Number of Participants Hospitalized During the Test Period [Weeks 1- 12]

   Number of participants hospitalized during Weeks 1-12 as self-reported in the Health Care Utilization portion of the Subject Outcome Questionaire.

2. Days of Hospitalization During the Test Period [Weeks 1-12]

   Number of days hospitalized during Weeks 1-12 as self-reported in the Health Care Utilization portion of the Subject Outcome Questionaire; participants who were not hospitalized had a value of 0 days.

3. Number of Hospitalizations During the Test Period [Weeks 1-12]

   Number of times participants were hospitalized as self-reported in the Health Care Utilization portion of the Subject Outcome Questionaire during Weeks 1-12

Secondary Outcome Measures

1. Total Hospital Costs During the Test Period [Weeks 1-12]

   The hospital bill database was used to determine the mean total hospital cost per participant during the test period. Participants who were not hospitalized had a cost of $0 imputed.

2. Change in Functional Assessment of Cancer Therapy (FACT)-Fatigue Score at Week 13 [Baseline (Week 1) and Week 13]

   The FACT-Fatigue scale comprises 13 questions evaluating the impact of anemia on cancer patients with various tumor types receiving chemotherapy. Fatigue scores range from 0 to 52, with a higher score indicating less fatigue.

3. Hemoglobin Response During the Test Period [Weeks 1-12]

   The number of participants achieving a hemoglobin response, defined as an increase in hemoglobin from baseline of ≥ 2.0 g/dL in the absence of red blood cell (RBC) transfusions during the preceding 28 days.

4. Hematopoietic Response During the Test Period [Weeks 1-12]

   The number of participants achieving a hematopoietic response, defined as an increase in hemoglobin from baseline of ≥ 2.0 g/dL or a concentration ≥ 12.0 g/dL both in the absence of red blood cell (RBC) transfusions during the preceding 28 days.

5. Change From Baseline in Hemoglobin Level [Baseline (Week 1) and Week 13]

   The difference between hemoglobin concentrations after 12 weeks of treatment and the Baseline hemoglobin concentration value (Study Day 1 sample prior to first dose of darbepoetin alfa).

6. Number of Participants With Red Blood Cell (RBC) Transfusions During the Test Period [Weeks 1-12]

   Number of participants with at least one RBC transfusion during Weeks 1 to 12.

7. Number of Units of Red Blood Cells Transfused During the Test Period [Weeks 1-12]

   The average number of standard units of red blood cells transfused during Weeks 1 to 12.

8. Number of Days of Red Blood Cell Transfusions During the Test Period [Weeks 1-12]

   The number of days when at least one red blood cell transfusion was administered during Weeks 1 to 12.

9. Number of Participants With Red Blood Cell (RBC) Transfusions During Weeks 5-12 [Weeks 5-12]

   The number of participants with at least one RBC transfusion during weeks 5 to 12.

10. Number of Units of Red Blood Cells Transfused During Weeks 5-12 [Weeks 5-12]

    The number of standard units of RBCs transfused during Weeks 5 to 12.

11. Number of Days of Red Blood Cell Transfusions During Weeks 5-12 [Weeks 5-12]

    The number of days when at least one RBC transfusion was administered during Weeks 5 to 12.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• nonmyeloid malignancies (including lymphocytic leukemias)

• anemia (hemoglobin concentration less than or equal to 11.0 g/dL) due to cancer and/or previous chemotherapy or radiotherapy

• Eastern Cooperative Oncology Group performance status of 0 to 2

• adequate liver and renal functions

• 18 years or older

Exclusion Criteria:

• history of recombinant human erythropoietin therapy, cytotoxic chemotherapy, or more than 30 Gy radiotherapy to the whole pelvis within 4 weeks before screening

• acute myelogenous leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome

• known hematologic disorders that could cause anemia

• inflammatory or cardiac disorders

• previous positive antibody response to any erythropoietic agent

• history of pure red cell aplasia

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00989092
• Other Study ID Numbers: 20000219
• First Posted: Oct 2, 2009
• Last Update Posted: Jan 29, 2014
• Last Verified: Dec 1, 2013

• Keywords provided by Amgen: anemia of cancer; darbepoetin alfa; Aranesp
• Additional relevant MeSH terms: Neoplasms; Anemia; Darbepoetin alfa

Study Results

Participant Flow

Recruitment Details	First Patient Randomized: 24-Jun-2002 Last Patient Randomized: 08-Aug-2003

Arm/Group Title	Darbepoetin Alfa 3 μg/kg	Observation
Arm/Group Description	Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Period Title: Overall Study
STARTED	228	59
Treated With Darbepoetin Alfa	226	33
COMPLETED	138	31
NOT COMPLETED	90	28

Baseline Characteristics

Arm/Group Title	Darbepoetin Alfa 3 μg/kg	Observation	Total
Arm/Group Description	Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.	Total of all reporting groups
Overall Participants	226	59	285
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	71.7 (10.4)	67.2 (12.5)	70.8 (11)
Sex: Female, Male (Count of Participants)
Female	131 58%	36 61%	167 58.6%
Male	95 42%	23 39%	118 41.4%
Race/Ethnicity, Customized (Participant) [Number]
White	188	46	234
Black	28	12	40
Asian	5	1	6
Other	5	0	5

Outcome Measures

1. Primary Outcome

Title	Number of Participants Hospitalized During the Test Period
Description	Number of participants hospitalized during Weeks 1-12 as self-reported in the Health Care Utilization portion of the Subject Outcome Questionaire.
Time Frame	Weeks 1- 12

Outcome Measure Data

Analysis Population Description

Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm. Patients also needed to have completed the baseline and at least 1 post-baseline subject outcome questionaire.

Arm/Group Title	Darbepoetin Alfa 3 μg/kg	Observation
Arm/Group Description	Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Measure Participants	215	45
Number [Participants]	23 10.2%	6 10.2%

2. Secondary Outcome

Title	Total Hospital Costs During the Test Period
Description	The hospital bill database was used to determine the mean total hospital cost per participant during the test period. Participants who were not hospitalized had a cost of $0 imputed.
Time Frame	Weeks 1-12

Outcome Measure Data

Analysis Population Description

Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm, and were included in the hospital bill database. Participants who were not hospitalized had a cost of $0 imputed.

Arm/Group Title	Darbepoetin Alfa 3 μg/kg	Observation
Arm/Group Description	Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Measure Participants	198	40
Mean (Standard Deviation) [dollars]	1474.58 (5528.61)	487.31 (1821.43)

3. Secondary Outcome

Title	Change in Functional Assessment of Cancer Therapy (FACT)-Fatigue Score at Week 13
Description	The FACT-Fatigue scale comprises 13 questions evaluating the impact of anemia on cancer patients with various tumor types receiving chemotherapy. Fatigue scores range from 0 to 52, with a higher score indicating less fatigue.
Time Frame	Baseline (Week 1) and Week 13

Outcome Measure Data

Analysis Population Description

Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm. Participants also needed to have completed the baseline and at least 1 post-baseline FACT-Fatigue questionaire. Last Value Carried Forward (LVCF) imputation used.

Arm/Group Title	Darbepoetin Alfa 3 μg/kg	Observation
Arm/Group Description	Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Measure Participants	215	45
Mean (Standard Deviation) [units on a scale]	6.0 (12.0)	2.2 (7.6)

4. Secondary Outcome

Title	Hemoglobin Response During the Test Period
Description	The number of participants achieving a hemoglobin response, defined as an increase in hemoglobin from baseline of ≥ 2.0 g/dL in the absence of red blood cell (RBC) transfusions during the preceding 28 days.
Time Frame	Weeks 1-12

Outcome Measure Data

Analysis Population Description

Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm. Patients also needed to have a baseline hemoglobin that was not affected by a red blood cell transfusion.

Arm/Group Title	Darbepoetin Alfa 3 μg/kg	Observation
Arm/Group Description	Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Measure Participants	220	55
Number [Participants]	128 56.6%	4 6.8%

5. Secondary Outcome

Title	Hematopoietic Response During the Test Period
Description	The number of participants achieving a hematopoietic response, defined as an increase in hemoglobin from baseline of ≥ 2.0 g/dL or a concentration ≥ 12.0 g/dL both in the absence of red blood cell (RBC) transfusions during the preceding 28 days.
Time Frame	Weeks 1-12

Outcome Measure Data

Analysis Population Description

Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm. Patients also needed to have a baseline hemoglobin that was not affected by a red blood cell transfusion.

Arm/Group Title	Darbepoetin Alfa 3 μg/kg	Observation
Arm/Group Description	Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Measure Participants	220	55
Number [Participants]	145 64.2%	10 16.9%

6. Secondary Outcome

Title	Change From Baseline in Hemoglobin Level
Description	The difference between hemoglobin concentrations after 12 weeks of treatment and the Baseline hemoglobin concentration value (Study Day 1 sample prior to first dose of darbepoetin alfa).
Time Frame	Baseline (Week 1) and Week 13

Outcome Measure Data

Analysis Population Description

Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm. Patients also needed to have a baseline hemoglobin that was not affected by a red blood cell transfusion. LVCF imputation was used.

Arm/Group Title	Darbepoetin Alfa 3 μg/kg	Observation
Arm/Group Description	Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Measure Participants	220	55
Mean (Standard Deviation) [g/dL]	2.1 (1.9)	0.1 (0.8)

7. Secondary Outcome

Title	Number of Participants With Red Blood Cell (RBC) Transfusions During the Test Period
Description	Number of participants with at least one RBC transfusion during Weeks 1 to 12.
Time Frame	Weeks 1-12

Outcome Measure Data

Analysis Population Description

Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm with available data.

Arm/Group Title	Darbepoetin Alfa 3 μg/kg	Observation
Arm/Group Description	Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Measure Participants	226	59
Number [Participants]	25 11.1%	11 18.6%

8. Primary Outcome

Title	Days of Hospitalization During the Test Period
Description	Number of days hospitalized during Weeks 1-12 as self-reported in the Health Care Utilization portion of the Subject Outcome Questionaire; participants who were not hospitalized had a value of 0 days.
Time Frame	Weeks 1-12

Outcome Measure Data

Analysis Population Description

Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm. Patients also needed to have completed the baseline and at least 1 post-baseline subject outcome questionaire.

Arm/Group Title	Darbepoetin Alfa 3 μg/kg	Observation
Arm/Group Description	Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Measure Participants	212	44
Mean (Standard Deviation) [days]	0.5 (2.2)	0.5 (1.7)

9. Primary Outcome

Title	Number of Hospitalizations During the Test Period
Description	Number of times participants were hospitalized as self-reported in the Health Care Utilization portion of the Subject Outcome Questionaire during Weeks 1-12
Time Frame	Weeks 1-12

Outcome Measure Data

Analysis Population Description

Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm. Patients also needed to have completed the baseline and at least 1 post-baseline subject outcome questionaire.

Arm/Group Title	Darbepoetin Alfa 3 μg/kg	Observation
Arm/Group Description	Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Measure Participants	215	45
Mean (Standard Deviation) [hospitalizations]	0.1 (0.5)	0.2 (0.4)

10. Secondary Outcome

Title	Number of Units of Red Blood Cells Transfused During the Test Period
Description	The average number of standard units of red blood cells transfused during Weeks 1 to 12.
Time Frame	Weeks 1-12

Outcome Measure Data

Analysis Population Description

Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm.

Arm/Group Title	Darbepoetin Alfa 3 μg/kg	Observation
Arm/Group Description	Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Measure Participants	226	59
Mean (Standard Deviation) [units of red blood cells]	0.4 (1.4)	0.9 (2.4)

11. Secondary Outcome

Title	Number of Days of Red Blood Cell Transfusions During the Test Period
Description	The number of days when at least one red blood cell transfusion was administered during Weeks 1 to 12.
Time Frame	Weeks 1-12

Outcome Measure Data

Analysis Population Description

Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm.

Arm/Group Title	Darbepoetin Alfa 3 μg/kg	Observation
Arm/Group Description	Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Measure Participants	226	59
Mean (Standard Deviation) [days]	0.2 (0.6)	0.4 (1.0)

12. Secondary Outcome

Title	Number of Participants With Red Blood Cell (RBC) Transfusions During Weeks 5-12
Description	The number of participants with at least one RBC transfusion during weeks 5 to 12.
Time Frame	Weeks 5-12

Outcome Measure Data

Analysis Population Description

Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm, and who were on-study as of the beginning of Week 5 (Study Day 29).

Arm/Group Title	Darbepoetin Alfa 3 μg/kg	Observation
Arm/Group Description	Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Measure Participants	215	47
Number [Participants]	16 7.1%	10 16.9%

13. Secondary Outcome

Title	Number of Units of Red Blood Cells Transfused During Weeks 5-12
Description	The number of standard units of RBCs transfused during Weeks 5 to 12.
Time Frame	Weeks 5-12

Outcome Measure Data

Analysis Population Description

Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm, and who were on-study as of the beginning of week 5 (study day 29).

Arm/Group Title	Darbepoetin Alfa 3 μg/kg	Observation
Arm/Group Description	Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Measure Participants	215	47
Mean (Standard Deviation) [units of red blood cells]	0.2 (1.0)	0.8 (1.8)

14. Secondary Outcome

Title	Number of Days of Red Blood Cell Transfusions During Weeks 5-12
Description	The number of days when at least one RBC transfusion was administered during Weeks 5 to 12.
Time Frame	Weeks 5-12

Outcome Measure Data

Analysis Population Description

Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm, and who were on-study as of the beginning of Week 5 (Study Day 29).

Arm/Group Title	Darbepoetin Alfa 3 μg/kg	Observation
Arm/Group Description	Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7.	Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL.
Measure Participants	215	47
Mean (Standard Deviation) [days]	0.1 (0.5)	0.4 (0.8)

Adverse Events

Time Frame	First dose through End of Study or 30 days after last dose, up to 25 weeks.
Adverse Event Reporting Description	The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Arm/Group Title	Treatment Arm		Observation Arm Treated		Observation Arm Not Treated
Arm/Group Description	Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at week 7 (to 5.0 μg/kg once every 2 weeks) or at week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at week 7.		Participants in the observation group who received darbepoetin alfa, initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participants hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL. Adverse events for participants in this group could have been reported at any time during the study; and therefore, may have occurred before darbepoetin alfa administration.		Participants in the observation group who did not receive any darbepoetin alfa treatment.
All Cause Mortality
	Treatment Arm		Observation Arm Treated		Observation Arm Not Treated
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Treatment Arm		Observation Arm Treated		Observation Arm Not Treated
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	65/226 (28.8%)		4/33 (12.1%)		4/26 (15.4%)
Blood and lymphatic system disorders
Anaemia	4/226 (1.8%)		1/33 (3%)		0/26 (0%)
Pancytopenia	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Thrombocytopenia	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Cardiac disorders
Bradycardia	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Cardio-respiratory arrest	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Gastrointestinal disorders
Abdominal pain	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Ascites	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Colitis	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Constipation	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Diarrhoea	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Gastrointestinal haemorrhage	2/226 (0.9%)		0/33 (0%)		0/26 (0%)
Intestinal perforation	2/226 (0.9%)		0/33 (0%)		0/26 (0%)
Nausea	2/226 (0.9%)		0/33 (0%)		0/26 (0%)
Oesophageal ulcer	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Small intestinal obstruction	2/226 (0.9%)		0/33 (0%)		0/26 (0%)
Vomiting	5/226 (2.2%)		1/33 (3%)		0/26 (0%)
General disorders
Asthenia	4/226 (1.8%)		0/33 (0%)		0/26 (0%)
Chest pain	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Fatigue	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Malaise	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Pain	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Pyrexia	3/226 (1.3%)		0/33 (0%)		0/26 (0%)
Hepatobiliary disorders
Bile duct obstruction	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Biliary colic	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Cholelithiasis	2/226 (0.9%)		0/33 (0%)		0/26 (0%)
Hepatic failure	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Infections and infestations
Abdominal abscess	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Bronchitis	0/226 (0%)		1/33 (3%)		0/26 (0%)
Cellulitis	0/226 (0%)		1/33 (3%)		0/26 (0%)
Lobar pneumonia	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Pneumonia	7/226 (3.1%)		2/33 (6.1%)		0/26 (0%)
Postoperative wound infection	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Sepsis	1/226 (0.4%)		0/33 (0%)		1/26 (3.8%)
Sinusitis	0/226 (0%)		1/33 (3%)		0/26 (0%)
Subcutaneous abscess	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Urinary tract infection	2/226 (0.9%)		0/33 (0%)		0/26 (0%)
Injury, poisoning and procedural complications
Radiation pneumonitis	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Investigations
Prothrombin time prolonged	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Metabolism and nutrition disorders
Dehydration	4/226 (1.8%)		1/33 (3%)		0/26 (0%)
Gout	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Hyperglycaemia	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Hypoglycaemia	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Hyponatraemia	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Back pain	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Pathological fracture	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Breast cancer	3/226 (1.3%)		0/33 (0%)		0/26 (0%)
Colon cancer metastatic	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Hepatic neoplasm malignant	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Lung neoplasm malignant	4/226 (1.8%)		0/33 (0%)		0/26 (0%)
Mesothelioma malignant	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Metastases to lung	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Metastases to spine	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Non-Hodgkin's lymphoma	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Non-small cell lung cancer	1/226 (0.4%)		1/33 (3%)		0/26 (0%)
Ovarian cancer	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Pleural mesothelioma	0/226 (0%)		0/33 (0%)		1/26 (3.8%)
Prostate cancer	3/226 (1.3%)		0/33 (0%)		1/26 (3.8%)
Rectal cancer	1/226 (0.4%)		0/33 (0%)		1/26 (3.8%)
Renal cell carcinoma stage unspecified	1/226 (0.4%)		0/33 (0%)		1/26 (3.8%)
Sarcoma	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Small cell lung cancer stage unspecified	2/226 (0.9%)		0/33 (0%)		0/26 (0%)
Nervous system disorders
Cerebral haemorrhage	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Cerebrovascular accident	2/226 (0.9%)		0/33 (0%)		0/26 (0%)
Convulsion	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Depressed level of consciousness	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Headache	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Hepatic encephalopathy	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Hydrocephalus	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Spinal cord compression	2/226 (0.9%)		0/33 (0%)		0/26 (0%)
Syncope	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Transient ischaemic attack	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Tremor	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Psychiatric disorders
Confusional state	2/226 (0.9%)		0/33 (0%)		0/26 (0%)
Renal and urinary disorders
Haematuria	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Renal failure	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Renal failure acute	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Renal failure chronic	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Chronic obstructive pulmonary disease	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Dyspnoea exacerbated	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Haemoptysis	2/226 (0.9%)		0/33 (0%)		0/26 (0%)
Pharyngeal haemorrhage	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Pleural effusion	4/226 (1.8%)		0/33 (0%)		0/26 (0%)
Pulmonary embolism	3/226 (1.3%)		0/33 (0%)		0/26 (0%)
Pulmonary oedema	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Surgical and medical procedures
Gastrostomy tube insertion	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Vascular disorders
Aortic aneurysm rupture	1/226 (0.4%)		0/33 (0%)		0/26 (0%)
Deep vein thrombosis	3/226 (1.3%)		0/33 (0%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	Treatment Arm		Observation Arm Treated		Observation Arm Not Treated
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	99/226 (43.8%)		21/33 (63.6%)		6/26 (23.1%)
Gastrointestinal disorders
Abdominal pain	2/226 (0.9%)		2/33 (6.1%)		0/26 (0%)
Constipation	13/226 (5.8%)		1/33 (3%)		1/26 (3.8%)
Diarrhoea	16/226 (7.1%)		4/33 (12.1%)		1/26 (3.8%)
Dyspepsia	4/226 (1.8%)		2/33 (6.1%)		0/26 (0%)
Gastrooesophageal reflux disease	2/226 (0.9%)		2/33 (6.1%)		0/26 (0%)
Haemorrhoids	2/226 (0.9%)		2/33 (6.1%)		0/26 (0%)
Nausea	5/226 (2.2%)		2/33 (6.1%)		0/26 (0%)
Rectal haemorrhage	2/226 (0.9%)		2/33 (6.1%)		0/26 (0%)
General disorders
Asthenia	22/226 (9.7%)		2/33 (6.1%)		2/26 (7.7%)
Fatigue	42/226 (18.6%)		6/33 (18.2%)		3/26 (11.5%)
Oedema peripheral	20/226 (8.8%)		1/33 (3%)		1/26 (3.8%)
Pain	9/226 (4%)		2/33 (6.1%)		1/26 (3.8%)
Infections and infestations
Nasopharyngitis	2/226 (0.9%)		2/33 (6.1%)		0/26 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	17/226 (7.5%)		4/33 (12.1%)		1/26 (3.8%)
Arthritis	2/226 (0.9%)		2/33 (6.1%)		0/26 (0%)
Back pain	8/226 (3.5%)		5/33 (15.2%)		1/26 (3.8%)
Neck pain	5/226 (2.2%)		2/33 (6.1%)		0/26 (0%)
Nervous system disorders
Dizziness	12/226 (5.3%)		3/33 (9.1%)		1/26 (3.8%)
Hypoaesthesia	1/226 (0.4%)		2/33 (6.1%)		0/26 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	11/226 (4.9%)		3/33 (9.1%)		0/26 (0%)
Dyspnoea	21/226 (9.3%)		6/33 (18.2%)		2/26 (7.7%)
Dyspnoea exertional	3/226 (1.3%)		2/33 (6.1%)		0/26 (0%)
Pharyngolaryngeal pain	7/226 (3.1%)		2/33 (6.1%)		0/26 (0%)
Pleural effusion	0/226 (0%)		2/33 (6.1%)		0/26 (0%)
Vascular disorders
Hot flush	2/226 (0.9%)		2/33 (6.1%)		0/26 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multi-center studies, the investigator agrees not to publish any results before the first multi-center publication.