NCT02174731

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of roxadustat compared to epoetin alfa for the treatment of anemia in chronic kidney disease patients on dialysis.

Trial Health

98
On Track

Trial Health Score

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

Strong global presence with extensive site network
Enrollment
2,133

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Jul 2014

Typical duration for phase_3

Geographic Reach
18 countries

188 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 24, 2014

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 25, 2014

Completed
6 days until next milestone

Study Start

First participant enrolled

July 1, 2014

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 26, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 26, 2018

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

December 16, 2019

Completed
Last Updated

December 16, 2019

Status Verified

November 1, 2019

Enrollment Period

4.2 years

First QC Date

June 24, 2014

Results QC Date

September 26, 2019

Last Update Submit

November 27, 2019

Conditions

Keywords

Renal,CKD,Epoetin alfa,Roxadustat,dialysis,anemia

Outcome Measures

Primary Outcomes (1)

  • Mean Change From Baseline in Hb Averaged Over Week 28 to Week 52

    Baseline Hb was defined as the mean of the three last central laboratory Hb values from the screening and randomization visits. Mean change in Hb from baseline to the participants mean level from Week 28 to Week 52 was analyzed using a missing at random (MAR) based multiple imputation Analysis of Covariance (ANCOVA). Baseline Hb was used as a covariate and treatment group, cardiovascular (CV) history, geographic region and dialysis duration as fixed effects. The adjusted least squares (LS) mean estimates of change from baseline during Week 28 to Week 52 are presented.

    Baseline (Day 1, Week 0), Week 28 to 52

Secondary Outcomes (7)

  • Change in Hb From Baseline to the Mean Level During the Evaluation Period (Week 28 to Week 36) Without Having Received Rescue Therapy Within 6 Weeks Prior to and During the 8-Week Evaluation Period

    Baseline (Day 1, Week 0), Week 28 to 36

  • Proportion of Total Time of Hb Within the Interval of >=10 g/dL From Week 28 to Week 52

    Week 28 to 52

  • Proportion of Total Time of Hb Within the Interval of 10 to 12 g/dL From Week 28 to Week 52

    Week 28 to 52

  • Mean Change in Low-Density Lipoprotein (LDL) Cholesterol From Baseline to Week 24

    Baseline (Day 1, Week 0) to Week 24

  • Mean Change in Hb From Baseline to the Participant's Mean Level Between Week 28 to Week 52 in Participants With Baseline High-Sensitivity C-Reactive Protein (hsCRP) Greater Than the Upper Limit of Normal (ULN)

    Baseline (Day 1, Week 0), Week 28 to 52

  • +2 more secondary outcomes

Study Arms (2)

Roxadustat

EXPERIMENTAL
Drug: Roxadustat

Epoetin alfa

ACTIVE COMPARATOR
Drug: Epoetin alfa

Interventions

Roxadustat will be administered orally three times a week (TIW) to achieve an Hb level of 11 g/dL and maintain a Hb level of 11±1 g/dL.

Roxadustat

Epoetin alfa will be administered TIW consistent with approved prescribing information for epoetin alfa to achieve an Hb level of 11 g/dL and maintain a Hb level of 11±1 g/dL.

Epoetin alfa

Eligibility Criteria

Age18 Years - 130 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Provision of Informed Consent prior to any study specific procedures
  • Age ≥18 years at screening visit 1
  • Previous versions of the protocol prior to US amendment ver 6.0 and outside of US amendment ver 7.0:
  • Receiving or initiating hemodialysis or peritoneal dialysis for treatment of native kidney end-stage renal disease (ESRD) at least 30 days prior to visit 1. Patients treated with hemodialysis must have access consisting of an arteriovenous fistula, AV graft, or tunneled (permanent) catheter. Patients on peritoneal dialysis must have a functioning peritoneal dialysis catheter in place.
  • Starting with US amendment ver. 6.0 and outside of US amendment ver 7.0 (changed to recruit incident dialysis patients only):
  • Receiving or initiating hemodialysis or peritoneal dialysis for treatment of native kidney end-stage renal disease (ESRD) for a minimum of 2 weeks and a maximum of 4 months prior to randomization. Patients treated with hemodialysis must have access consisting of an arteriovenous fistula, AV graft, or tunneled (permanent) catheter. Patients on peritoneal dialysis must have a functioning peritoneal dialysis catheter in place.
  • Two central laboratory Hb values during the screening period, obtained at least 7 days apart, must be \<12 g/dL in patients currently treated with an erythropoietin analogue or \<10 g/dL in patients not currently treated with an erythropoietin analogue. Patients are considered not currently treated if they have not received either Mircera® for at least 8 weeks or any other erythropoietin analogue for at least 4 weeks prior to visit 1.
  • Ferritin ≥100 ng/mL at randomization (obtained from screening visit)
  • TSAT ≥20% at randomization (obtained from screening visit)
  • Serum folate level ≥ lower limit of normal (LLN) at randomization (obtained from screening visit)
  • Serum vitamin B12 level ≥ LLN at randomization (obtained from screening visit)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3x upper limit of normal (ULN), and total bilirubin (Tbili) ≤1.5 x ULN at randomization (obtained from screening visit)
  • Body weight 45 to 160 kg (prescribed dry weight)

You may not qualify if:

  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
  • Previous randomisation in the present study
  • New York Heart Association Class III or IV congestive heart failure at enrolment
  • Myocardial infarction, acute coronary syndrome, stroke, seizure or a thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism) within 12 weeks prior to randomization
  • History of chronic liver disease (e.g., chronic infectious hepatitis, chronic auto-immune liver disease, cirrhosis or fibrosis of the liver)
  • Known hereditary hematologic disease such as thalassemia, sickle cell anemia, a history of pure red cell aplasia or other known causes for anemia other than CKD
  • Known and untreated retinal vein occlusion or known and untreated proliferative diabetic retinopathy (risk for retinal vein thrombosis)
  • Diagnosis or suspicion (e.g. complex kidney cyst of Bosniak Category IIF, III or IV) of renal cell carcinoma on renal ultrasound (or other imaging procedure e.g. CT scan or MRI) conducted at screening or within 12 weeks prior to randomization.
  • Uncontrolled hypertension at the time of randomization (defined as systolic BP ≥180 mmHg or diastolic BP ≥100 mmHg on repeated measurement post-dialysis in hemodialysis patients or at any time in peritoneal dialysis patients), contraindication to epoetin alfa treatment (e.g., pure red cell aplasia, hypersensitivity or know inability to tolerate epoetin alfa)
  • History of prostate cancer, breast cancer or any other malignancy, except the following: cancers determined to be cured or in remission for ≥5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ or resected colonic polyps.
  • Positive for any of the following: human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus antibody (anti-HCV Ab)
  • Chronic inflammatory diseases such as rheumatoid arthritis, SLE, ankylosing spondylitis, psoriatic arthritis or inflammatory bowel disease that is determined to be the principal cause of anemia
  • Known hemosiderosis, hemochromatosis or hypercoagulable condition
  • Any prior organ transplant with the exception of an autologous renal transplant or a renal transplant that was subsequently removed ("explanted") or scheduled organ transplantation date
  • Any red blood cell (RBC) transfusion during the screening period
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (188)

Research Site

Huntsville, Alabama, 35805, United States

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El Centro, California, 92243, United States

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Fairfield, California, 94534, United States

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Glendale, California, 91205, United States

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Long Beach, California, 90802, United States

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Long Beach, California, 90807, 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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Northridge, California, 91324, United States

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Ontario, California, 91762, United States

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Orange, California, 92868, United States

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Riverside, California, 92503, United States

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Sacramento, California, 95825, United States

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Sun Valley, California, 91352, United States

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Whittier, California, 90602, United States

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Whittier, California, 90606, United States

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Denver, Colorado, 80230, United States

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New Haven, Connecticut, 06510, United States

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Miami Gardens, Florida, 33169, United States

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River Forest, Illinois, 60305, United States

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Wichita, Kansas, 67214, United States

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Baton Rouge, Louisiana, 70808, United States

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Lanham, Maryland, 20706, United States

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Plymouth, Massachusetts, 02360, United States

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Roseville, Michigan, 48066, United States

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Gulfport, Mississippi, 39501, United States

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Kansas City, Missouri, 64111, United States

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Reno, Nevada, 89511, United States

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Paterson, New Jersey, 07504, United States

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Great Neck, New York, 11021, United States

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Orchard Park, New York, 14127, United States

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The Bronx, New York, 10461, United States

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Asheville, North Carolina, 28805, United States

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Charlotte, North Carolina, 28207, United States

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Wilmington, North Carolina, 28401, United States

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Cincinnati, Ohio, 45206, United States

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Shawnee, Oklahoma, 74804, United States

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Bethlehem, Pennsylvania, 18017, United States

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Philadelphia, Pennsylvania, 19106, United States

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East Providence, Rhode Island, 02914, United States

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Austin, Texas, 78756, United States

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Austin, Texas, 78758, United States

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Houston, Texas, 77004, United States

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Houston, Texas, 77091, United States

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San Antonio, Texas, 78212, United States

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San Antonio, Texas, 78222, United States

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San Antonio, Texas, 78229, United States

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Newport News, Virginia, 23605, United States

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Sterling, Virginia, 20164, United States

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Bluefield, West Virginia, 24701, United States

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Camperdown, 2050, Australia

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Clayton, 3168, Australia

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Concord, 2139, Australia

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Launceston, 7250, Australia

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Prahan, 3004, Australia

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St Leonards, 2065, Australia

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Wahroonga, 2076, Australia

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Botevgrad, 2140, Bulgaria

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Dupnitsa, 2600, Bulgaria

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Gotse Delchev, 2900, Bulgaria

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Haskovo, 6300, Bulgaria

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Razlog, 2760, Bulgaria

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Samokov, 2000, Bulgaria

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Sandanski, 2800, Bulgaria

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Shumen, 9700, Bulgaria

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Silistra, Bulgaria

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Sliven, 8800, Bulgaria

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Smolyan, 3700, Bulgaria

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Yambol, 8600, Bulgaria

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Edmonton, Alberta, T6G 2B7, Canada

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Kamloops, British Columbia, V2C 2T1, Canada

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Saint John, New Brunswick, E2L 4L2, Canada

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Sydney, Nova Scotia, B1P 1P3, Canada

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Brampton, Ontario, L6R 3J7, Canada

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Oshawa, Ontario, L1G 2B9, Canada

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Scarborough Village, Ontario, M1P 2V5, Canada

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Toronto, Ontario, M3M 0B2, Canada

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Greenfield Park, Quebec, J4V 2H1, Canada

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Montreal, Quebec, H2X 3J4, Canada

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Montreal, Quebec, H4J 1C5, Canada

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Québec, Quebec, G1R 2J6, Canada

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Brno, 625 00, Czechia

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Prague, 140 00, Czechia

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Prague, 140 21, Czechia

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Prague, 190 61, Czechia

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Rychnov nad Kněžnou, 516 01, Czechia

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Slaný, 274 01, Czechia

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Tábor, 390 03, Czechia

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Ústí nad Labem, 401 13, Czechia

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Ajka, 8400, Hungary

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Budapest, 1076, Hungary

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Budapest, 1077, Hungary

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Budapest, 1097, Hungary

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Debrecen, 4043, Hungary

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Miskolc, 3526, Hungary

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Nagykanizsa, 8800, Hungary

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Székesfehérvár, 8000, Hungary

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Tatabánya, 2800, Hungary

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Chennai, 600006, India

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Ghaziabad NCR, 201012, India

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Hyderabad, 500018, India

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Kolkata, 700027, India

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Lucknow, 226003, India

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Maharashtra, 411013, India

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Mumbai, 400008, India

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Mysore, 570004, India

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Nadiād, 387001, India

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New Delhi, 110017, India

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New Delhi, 110060, India

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Pune, 411001, India

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Vellore, 632004, India

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Vijayawada, 520 008, India

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Aguascalientes, 20219, Mexico

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Guadalajara, 44670, Mexico

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México, 06700, Mexico

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Veracruz, 91900, Mexico

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Lima, 14, Peru

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Lima, L27, Peru

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Lima, LIMA 01, Peru

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Cebu City, 6000, Philippines

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Iloilo City, 5000, Philippines

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Ciechanów, 06-400, Poland

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Gmina Końskie, 26-200, Poland

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Katowice, 40-752, Poland

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Lodz, 90-153, Poland

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Lodz, 92-213, Poland

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Pszczyna, 43-200, Poland

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Suwałki, 16-400, Poland

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Tarnów, 33-100, Poland

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Warsaw, 02-758, Poland

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Arkhangelsk, 163001, Russia

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Barnaul, 656024, Russia

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Irkutsk, 664049, Russia

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Izhevsk, 426035, Russia

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Kemerovo, 650066, Russia

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Moscow, 105229, Russia

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Moscow, 123182, Russia

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Nizhny Novgorod, 603126, Russia

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Penza, 440034, Russia

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Perm, 614000, Russia

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Pyatigorsk, 357500, Russia

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Ryazan, 390027, Russia

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Saint Petersburg, 191015, Russia

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Ufa, 450071, Russia

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Banská Bystrica, 97517, Slovakia

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Banská Bystrica, Slovakia

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Bratislava, 82606, Slovakia

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Bratislava, 831 03, Slovakia

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Košice, 04011, Slovakia

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Kráľovský Chlmec, 077 01, Slovakia

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Nové Zámky, 940 34, Slovakia

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Zvolen, 960 01, Slovakia

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Almería, 04009, Spain

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Barcelona, 08029, Spain

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Granollers (Barcelona), 08400, Spain

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Málaga, 29010, Spain

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Seville, 41013, Spain

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Seville, 41071, Spain

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Tarragona, 43007, Spain

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Valencia, 46017, Spain

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Karlstad, 651 85, Sweden

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Stockholm, 141 86, Sweden

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Uppsala, 751 85, Sweden

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Västerås, 721 89, Sweden

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Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Chernivtsi, 58002, Ukraine

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Dnipro, 49005, Ukraine

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Ivano-Frankivsk, 76008, Ukraine

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Ivano-Frankivsk, 76018, Ukraine

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Kyiv, 01601, Ukraine

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Kyiv, 02125, Ukraine

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Kyiv, 04050, Ukraine

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Kyiv, 04107, Ukraine

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Odesa, 65025, Ukraine

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Odesa, 65074, Ukraine

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Poltava, 36024, Ukraine

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Ternopil, 46002, Ukraine

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Uzhhorod, 88006, Ukraine

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Vinnytsia, 21018, Ukraine

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Zaporizhzhya, 69001, Ukraine

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Zaporizhzhya, 69118, Ukraine

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Zaporizhzhya, 69600, Ukraine

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Can Tho, 900000, Vietnam

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Hanoi, 100000, Vietnam

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Hochiminh, 700000, Vietnam

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Huế, 530000, Vietnam

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Related Publications (4)

  • Hamano T, Yamaguchi Y, Goto K, Martin S, Jiletcovici A, Dellanna F, Akizawa T, Barratt J. Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Four Global Roxadustat Phase 3 Trials. Adv Ther. 2024 Apr;41(4):1553-1575. doi: 10.1007/s12325-023-02728-2. Epub 2024 Feb 16.

  • Barratt J, Dellanna F, Portoles J, Choukroun G, De Nicola L, Young J, Dimkovic N, Reusch M. Safety of Roxadustat Versus Erythropoiesis-Stimulating Agents in Patients with Anemia of Non-dialysis-Dependent or Incident-to-Dialysis Chronic Kidney Disease: Pooled Analysis of Four Phase 3 Studies. Adv Ther. 2023 Apr;40(4):1546-1559. doi: 10.1007/s12325-023-02433-0. Epub 2023 Feb 7.

  • Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.

  • Fishbane S, Pollock CA, El-Shahawy M, Escudero ET, Rastogi A, Van BP, Frison L, Houser M, Pola M, Little DJ, Guzman N, Pergola PE. Roxadustat Versus Epoetin Alfa for Treating Anemia in Patients with Chronic Kidney Disease on Dialysis: Results from the Randomized Phase 3 ROCKIES Study. J Am Soc Nephrol. 2022 Apr;33(4):850-866. doi: 10.1681/ASN.2020111638.

Related Links

MeSH Terms

Conditions

Anemia

Interventions

roxadustatEpoetin Alfa

Condition Hierarchy (Ancestors)

Hematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

ErythropoietinColony-Stimulating FactorsGlycoproteinsGlycoconjugatesCarbohydratesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological Factors

Limitations and Caveats

27 participants were excluded from the analysis due to Good Clinical Practice violations or system technical issues (17 in the roxadustat group and 10 in the epoetin alfa group).

Results Point of Contact

Title
Global Clinical Lead
Organization
AstraZeneca

Study Officials

  • Steven Fishbane, MD

    Chief Division of Kidney Diseases and Hypertension, North Shore University Hospital, Great Neck, NY, USA

    PRINCIPAL INVESTIGATOR
  • Mark Houser, MD

    AZ R&D, Gaithersburg, USA

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 24, 2014

First Posted

June 25, 2014

Study Start

July 1, 2014

Primary Completion

September 26, 2018

Study Completion

September 26, 2018

Last Updated

December 16, 2019

Results First Posted

December 16, 2019

Record last verified: 2019-11

Locations