NCT01652872

Brief Summary

A phase 3, multicenter, randomized, double-blind, parallel group study. Anemic subjects with chronic kidney disease (CKD) and not on dialysis will be randomized 1:1 to 1 of 2 dosing strategies to evaluate the proportion of subjects receiving at least one red blood cell (RBC) transfusion. In the haemoglobin (Hb)-based titration group, darbepoetin alfa doses will be titrated to maintain Hb ≥ 10.0 grams/deciliter (g/dL). In the fixed dose group, subjects will receive a fixed dose of darbepoetin alfa. Treatment group, darbepoetin alfa doses, and protocol specified Hb concentrations will be blinded. Subjects will be followed for approximately 2 years from the date of randomization.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
756

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Jul 2012

Longer than P75 for phase_3

Geographic Reach
2 countries

249 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 7, 2012

Completed
2 months until next milestone

First Posted

Study publicly available on registry

July 30, 2012

Completed
Same day until next milestone

Study Start

First participant enrolled

July 30, 2012

Completed
5.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 19, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 19, 2017

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

November 8, 2018

Completed
Last Updated

September 21, 2022

Status Verified

September 1, 2022

Enrollment Period

5.2 years

First QC Date

June 7, 2012

Results QC Date

October 11, 2018

Last Update Submit

September 8, 2022

Conditions

Keywords

anemiachronic kidney diseasekidney diseaserenal failure

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants in Receipt of 1 or More RBC Transfusions

    The percentage of participants receiving at least 1 RBC transfusion during the evaluation period was recorded for each treatment group. The evaluation period began from the date of randomization, and participants were censored at the last dose of investigational product plus 3 months or end of study, whichever was earlier (on-treatment approach).

    From randomization until the end of study, up to week 101.

Secondary Outcomes (4)

  • Mean Number of Units of RBC Transfused

    From randomization until the end of study, up to week 101.

  • Time to First RBC Transfusion

    From randomization until the end of study, up to week 101.

  • Mean Achieved Hb Concentration While Receiving Investigational Product

    From week 13 until the end of study, up to week 101.

  • Geometric Mean Cumulative Dose of Darbepoetin Alfa Per 4 Weeks

    From randomization until the end of study, up to week 101.

Study Arms (2)

Hb-Based Titration Group

ACTIVE COMPARATOR

Participants received darbepoetin alfa as a subcutaneous (SC) injection once every 4 weeks (Q4W) for up to 96 weeks. The dose of darbepoetin alfa was titrated based on the Hb concentration on the date of the visit, the corresponding Hb rate of rise (ROR), and the previously assigned dose. Doses were reduced if Hb exceeded 10.5 g/dL or Hb ROR exceeded 1.0 g/dL/4W. When darbepoetin alfa therapy was withheld per the dosing algorithm, placebo was administered. The starting dose of darbepoetin alfa was 0.45 micrograms/kilogram (mcg/kg) and the protocol specified doses ranged from 10 to 300 mcg.

Biological: Darbepoetin alfaOther: Placebo

Fixed Dose Group

EXPERIMENTAL

Participants received darbepoetin alfa as a SC injection Q4W at the same dose as assigned at the time of randomization for the duration of the 96 week treatment period. There was 1 exception to the fixed dose strategy: if the Hb was \> 12.0 g/dL, darbepoetin alfa therapy was withheld and placebo administered. Once the Hb fell to \< 10.0 g/dL, darbepoetin alfa therapy resumed at the same dose. The starting dose of darbepoetin alfa was 0.45 mcg/kg and the protocol specified doses ranged from 10 to 300 mcg.

Biological: Darbepoetin alfaOther: Placebo

Interventions

Darbepoetin alfa was presented as single use prefilled syringes (PFS). Investigational product was administered SC Q4W for the duration of the treatment period.

Also known as: Aranesp
Fixed Dose GroupHb-Based Titration Group
PlaceboOTHER

Placebo was presented as single use PFS. Participants received a SC placebo injection in place of darbepoetin alfa therapy when the dose of study drug was withheld per the dosing algorithm for the duration of the treatment period.

Fixed Dose GroupHb-Based Titration Group

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Clinical history of advanced CKD not on dialysis with at least 1 historic estimated glomerular filtration rate (eGFR) \< 45.0 mL/mi)/1.73 m2 at least 12 weeks prior to screening
  • Not currently receiving dialysis with an eGFR \< 45.0 mL/min/1.73m2, per the central laboratory during screening
  • Chronic anemia due to renal failure
  • Two Hb concentrations \< 10.0 g/dL, at least 2 weeks apart during screening using the modified Hb point of care (POC) device
  • Iron replete, defined as a transferrin saturation (TSAT) ≥ 20% and a ferritin ≥ 100 ng/mL, per the central laboratory during screening
  • Vitamin B12 and folate replete, defined as a vitamin B12 level \> 180 pg/mL and a folate concentration \> 7 nmol/L, per the central laboratory during screening
  • Clinically stable in the opinion of the investigator
  • Subject has provided written informed consent

You may not qualify if:

  • Systemic hematologic disease (eg, sickle cell anemia, myelodysplastic syndrome, hematologic malignancy)
  • Current or prior malignancy within 5 years of screening, with the exception of non-melanoma skin cancers and cervical intraepithelial neoplasia
  • Treatment for any malignancy (eg, radiation, chemotherapy, hormone therapy, or biologics) within 5 years of screening, with the exception of locally excised non-melanoma skin cancer or cervical intraepithelial neoplasia
  • Female subject not willing to use highly effective methods of birth control during treatment and for 4 weeks after the end of treatment
  • Subject is pregnant or breast feeding, or might become pregnant during the study or within 4 weeks after the end of treatment
  • Currently receiving intravenous (IV) antibiotics for treatment of an active infection
  • Known Human Immunodeficiency Virus (HIV) positive
  • Currently receiving systemic immunosuppressive therapy with the exception of prednis(ol)one ≤ 10 mg per day (or the steroid equivalent)
  • History of any organ transplant
  • Currently enrolled in another interventional study (eg, studies which require medical device use or drug therapy or with protocol required procedures), or less than 4 weeks since ending another interventional study(s) or receiving investigational agent(s)
  • Known neutralizing anti-erythropoietic protein antibodies
  • Known sensitivity to any of the products to be administered during dosing
  • Previously enrolled in this study
  • Not expected to be available for protocol required study visits or procedures to the best of the subject and investigator's knowledge
  • Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or comply with all required study procedures
  • +15 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (249)

Research Site

Anniston, Alabama, 36207, United States

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Birmingham, Alabama, 35235, United States

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Huntsville, Alabama, 35801, United States

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Mobile, Alabama, 36608, United States

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Mobile, Alabama, 36617, United States

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Montgomery, Alabama, 36106, United States

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Goodyear, Arizona, 85395, United States

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Peoria, Arizona, 85381, United States

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Phoenix, Arizona, 85004, United States

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Phoenix, Arizona, 85012, United States

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Phoenix, Arizona, 85032, United States

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Tempe, Arizona, 85284, United States

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Little Rock, Arkansas, 72204, United States

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Alhambra, California, 91801, United States

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Anaheim, California, 92805, United States

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Azusa, California, 91702, United States

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Bakersfield, California, 93301, United States

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Bakersfield, California, 93309, United States

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Bell Gardens, California, 90201, United States

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Beverly Hills, California, 90211, United States

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Cerritos, California, 90703, United States

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Chula Vista, California, 91910, United States

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Cudahy, California, 90201, United States

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El Centro, California, 92243, United States

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Fountain Valley, California, 92708, United States

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Fullerton, California, 92835, United States

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Garden Grove, California, 92844, United States

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Glendale, California, 91204, United States

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Granada Hills, California, 91344, United States

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Huntington Beach, California, 92648, United States

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Inglewood, California, 90301, United States

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La Jolla, California, 92037, United States

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La Mesa, California, 91942, United States

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Laguna Hills, California, 92653, United States

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Lakewood, California, 90712, United States

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Lancaster, California, 93534, United States

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Lomita, California, 90717, United States

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Long Beach, California, 90813, United States

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Los Angeles, California, 90015, United States

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Los Angeles, California, 90017, United States

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Los Angeles, California, 90022, United States

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Los Angeles, California, 90025, United States

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Lynwood, California, 90262, United States

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Mission Hills, California, 91345, United States

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Modesto, California, 95350, United States

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Northridge, California, 91324, United States

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Northridge, California, 91325, United States

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Orange, California, 92868, United States

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Rancho Mirage, California, 92270, United States

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Redondo Beach, California, 90277, United States

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Riverside, California, 92505, United States

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Sacramento, California, 95825, United States

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San Dimas, California, 91773, United States

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Whittier, California, 90602, United States

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Whittier, California, 90603, United States

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Yuba City, California, 95991, United States

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Arvada, Colorado, 80002, United States

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Westminster, Colorado, 80031, United States

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Middlebury, Connecticut, 06762, United States

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New Haven, Connecticut, 06511, United States

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North Haven, Connecticut, 06473, United States

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Washington D.C., District of Columbia, 20037, United States

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Boynton Beach, Florida, 33472, United States

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Coral Springs, Florida, 33071, United States

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Daytona Beach, Florida, 32117, United States

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DeLand, Florida, 32720, United States

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Fort Lauderdale, Florida, 33308, United States

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Hollywood, Florida, 33021, United States

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Hudson, Florida, 34667, United States

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Jacksonville, Florida, 32216, United States

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Jacksonville Beach, Florida, 32250, United States

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Lauderdale Lakes, Florida, 33313, United States

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Melbourne, Florida, 32901, United States

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Melbourne, Florida, 32935, United States

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Miami, Florida, 33144, United States

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Miami, Florida, 33150, United States

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Miami, Florida, 33166, United States

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Miami, Florida, 33173, United States

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Miami Beach, Florida, 33140, United States

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Naples, Florida, 34110, United States

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New Port Richey, Florida, 34652, United States

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New Port Richey, Florida, 34653, United States

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Orlando, Florida, 32804, United States

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Pembroke Pines, Florida, 33028, United States

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Port Charlotte, Florida, 33952, United States

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Summerfield, Florida, 34491, United States

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Tampa, Florida, 33603, United States

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Tampa, Florida, 33612, United States

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Tampa, Florida, 33614, United States

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Atlanta, Georgia, 30342, United States

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Augusta, Georgia, 30909, United States

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Canton, Georgia, 30114, United States

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Macon, Georgia, 31217, United States

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Newnan, Georgia, 30265, United States

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Honolulu, Hawaii, 96817, United States

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Meridian, Idaho, 83642, United States

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Chicago, Illinois, 60612, United States

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Chicago, Illinois, 60616, United States

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Chicago, Illinois, 60637, United States

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Evanston, Illinois, 60201, United States

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Peoria, Illinois, 61603, United States

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Quincy, Illinois, 62301, United States

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Columbus, Indiana, 47201, United States

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Michigan City, Indiana, 46360, United States

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Ames, Iowa, 50010, United States

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Kansas City, Kansas, 66160, United States

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Wichita, Kansas, 67214-2998, United States

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Lexington, Kentucky, 40504, United States

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Paducah, Kentucky, 42003, United States

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Baton Rouge, Louisiana, 70808, United States

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Lafayette, Louisiana, 70503, United States

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Metairie, Louisiana, 70006, United States

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Natchitoches, Louisiana, 71457, United States

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New Orleans, Louisiana, 70112, United States

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Ruston, Louisiana, 71270, United States

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Shreveport, Louisiana, 71101, United States

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Rockport, Maine, 04856, United States

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Bethesda, Maryland, 20814, United States

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Oxon Hill, Maryland, 20745, United States

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Framingham, Massachusetts, 01702, United States

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Plymouth, Massachusetts, 02360, United States

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Springfield, Massachusetts, 01107, United States

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Flint, Michigan, 48504, United States

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Grand Rapids, Michigan, 49525, United States

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Kalamazoo, Michigan, 49007, United States

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Midland, Michigan, 48640, United States

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Pontiac, Michigan, 48341, United States

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Royal Oak, Michigan, 48073, United States

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Southgate, Michigan, 48195, United States

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Columbus, Mississippi, 39705, United States

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Gulfport, Mississippi, 39501, United States

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City of Saint Peters, Missouri, 63376, United States

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Kansas City, Missouri, 64111, United States

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Kansas City, Missouri, 64114, United States

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Lincoln, Nebraska, 68510, United States

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North Platte, Nebraska, 69101, United States

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Henderson, Nevada, 89052, United States

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Las Vegas, Nevada, 89106, United States

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Eatontown, New Jersey, 07724, United States

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Livingston, New Jersey, 07039, United States

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Toms River, New Jersey, 08755, United States

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Voorhees Township, New Jersey, 08043, United States

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Albany, New York, 12208, United States

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Brooklyn, New York, 11203, United States

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Buffalo, New York, 14215, United States

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Flushing, New York, 11355, United States

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Great Neck, New York, 11021, United States

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Mineola, New York, 11501, United States

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New York, New York, 10037, United States

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Orchard Park, New York, 14127, United States

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Rochester, New York, 14642, United States

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Rosedale, New York, 11422, United States

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The Bronx, New York, 10461, United States

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Asheville, North Carolina, 28801, United States

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Chapel Hill, North Carolina, 27599, United States

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Durham, North Carolina, 27704, United States

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Greensboro, North Carolina, 27408, United States

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Greenville, North Carolina, 27834, United States

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Kinston, North Carolina, 28504, United States

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Mooresville, North Carolina, 28117, United States

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New Bern, North Carolina, 28562, United States

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Statesville, North Carolina, 28625, United States

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Wilmington, North Carolina, 28401, United States

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Winston-Salem, North Carolina, 27103, United States

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Winston-Salem, North Carolina, 27157, United States

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Fargo, North Dakota, 58103, United States

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Fargo, North Dakota, 58122, United States

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Grand Forks, North Dakota, 58201, United States

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Columbus, Ohio, 43210, United States

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Columbus, Ohio, 43215, United States

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Marion, Ohio, 43302, United States

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Poland, Ohio, 44514, United States

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Toledo, Ohio, 43606, United States

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Willoughby Hills, Ohio, 44094, United States

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Oklahoma City, Oklahoma, 73116, United States

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Tulsa, Oklahoma, 74120, United States

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Portland, Oregon, 97210, United States

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Portland, Oregon, 97213, United States

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Roseburg, Oregon, 97471, United States

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Beaver, Pennsylvania, 15009, United States

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Bethlehem, Pennsylvania, 18017, United States

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Doylestown, Pennsylvania, 18901, United States

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Duncansville, Pennsylvania, 16635, United States

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Philadelphia, Pennsylvania, 19102, United States

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Philadelphia, Pennsylvania, 19118, United States

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Philadelphia, Pennsylvania, 19140, United States

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Anderson, South Carolina, 29621, United States

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Columbia, South Carolina, 29203, United States

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Greenville, South Carolina, 29605, United States

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Orangeburg, South Carolina, 29118, United States

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Bristol, Tennessee, 37620, United States

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Columbia, Tennessee, 38401, United States

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Dyersburg, Tennessee, 38024, United States

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Franklin, Tennessee, 37064, United States

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Jackson, Tennessee, 38305, United States

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Kingsport, Tennessee, 37660, United States

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Knoxville, Tennessee, 37923, United States

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Memphis, Tennessee, 38163, United States

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Arlington, Texas, 76015, United States

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Austin, Texas, 78705, United States

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Austin, Texas, 78751, United States

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Austin, Texas, 78758, United States

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Corsicana, Texas, 75110, United States

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Dallas, Texas, 75390, United States

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Edinburg, Texas, 78539, United States

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El Paso, Texas, 79905, United States

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Fort Worth, Texas, 76104, United States

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Frisco, Texas, 75035, United States

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Greenville, Texas, 75402, United States

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Houston, Texas, 77004, United States

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Houston, Texas, 77008, United States

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Houston, Texas, 77030, United States

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Houston, Texas, 77031, United States

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Houston, Texas, 77036, United States

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Houston, Texas, 77054, United States

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Houston, Texas, 77057, United States

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Houston, Texas, 77074, United States

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Houston, Texas, 77099, United States

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Lubbock, Texas, 79430, United States

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Lufkin, Texas, 75904, United States

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McAllen, Texas, 78503, United States

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McKinney, Texas, 75069, United States

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San Antonio, Texas, 78205, United States

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San Antonio, Texas, 78215, United States

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San Antonio, Texas, 78224, United States

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San Antonio, Texas, 78228, United States

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San Antonio, Texas, 78229, United States

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Temple, Texas, 76502, United States

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Burlington, Vermont, 05401, United States

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Alexandria, Virginia, 22304, United States

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Chesapeake, Virginia, 23320, United States

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Fairfax, Virginia, 22030, United States

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Fairfax, Virginia, 22033, United States

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Hampton, Virginia, 23666, United States

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Manassas, Virginia, 20110, United States

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Mechanicsville, Virginia, 23116, United States

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Norfolk, Virginia, 23502, United States

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Richmond, Virginia, 23219, United States

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Richmond, Virginia, 23229, United States

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Richmond, Virginia, 23298-0160, United States

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Silverdale, Washington, 98383, United States

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Bluefield, West Virginia, 24701, United States

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Milwaukee, Wisconsin, 53226, United States

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Caguas, 00725, Puerto Rico

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Ponce, 00716, Puerto Rico

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Ponce, 00717, Puerto Rico

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Rio Piedras, 00935, Puerto Rico

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San Juan, 00909, Puerto Rico

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San Juan, 00918, Puerto Rico

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Related Publications (1)

  • Toto R, Petersen J, Berns JS, Lewis EF, Tran Q, Weir MR. A Randomized Trial of Strategies Using Darbepoetin Alfa To Avoid Transfusions in CKD. J Am Soc Nephrol. 2021 Feb;32(2):469-478. doi: 10.1681/ASN.2020050556. Epub 2020 Dec 7.

    PMID: 33288629BACKGROUND

Related Links

MeSH Terms

Conditions

AnemiaRenal Insufficiency, ChronicKidney DiseasesRenal Insufficiency

Interventions

Darbepoetin alfa

Condition Hierarchy (Ancestors)

Hematologic DiseasesHemic and Lymphatic DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

ErythropoietinColony-Stimulating FactorsGlycoproteinsGlycoconjugatesCarbohydratesProteinsAmino Acids, Peptides, and Proteins

Results Point of Contact

Title
Study Director
Organization
Amgen Inc.

Study Officials

  • MD

    Amgen

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 7, 2012

First Posted

July 30, 2012

Study Start

July 30, 2012

Primary Completion

October 19, 2017

Study Completion

October 19, 2017

Last Updated

September 21, 2022

Results First Posted

November 8, 2018

Record last verified: 2022-09

Locations