Clinical trial NCT01887600: Roxadustat in the Treatment of Anemia in Chronic Kidney Disease Patients Not Requiring Dialysis
Official title: A Phase 3, Randomized, Double-Blind, Placebo Controlled Study of the Efficacy and Safety of Roxadustat for the Treatment of Anemia in Chronic Kidney Disease Patients Not on Dialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anemia in Chronic Kidney Disease in Non-dialysis Patients
Keywords: anemia
chronic kidney disease (CKD)
Hemoglobin (Hb)
non-dialysis
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: FibroGen
First posted: 2013-06-27
Enrollment: 594
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was conducted to treat anemia in patients with chronic kidney disease. Anemia is a reduced number of red blood cells or hemoglobin. Hemoglobin is important for the transport of oxygen in your blood. The purpose of the study was to see if Roxadustat is both effective and safe as a treatment for anemia in patients with chronic kidney disease.

Detailed description: The study consisted of three study periods as follows:

* Screening period: up to 6 weeks
* Treatment period: minimum 52 weeks (primary treatment period) up to a maximum of 104 weeks (extended treatment period)
* Post-Treatment Follow-Up period: 4 weeks

Eligibility criteria: Inclusion criteria:

* Participant has a diagnosis of chronic kidney disease, with Kidney Disease Outcomes Quality Initiative (KDOQI) Stage 3, 4 or 5, not receiving dialysis; with an Estimated Glomerular Filtration Rate (eGFR) \<60 mL/min/1.73 m\^2 estimated using the abbreviated 4-variable Modification of Diet in Renal Disease (MDRD) equation.
* The mean of the Participant's three most recent Hb values during the Screening period, obtained at least 4 days apart, must be less than or equal to 10.0 g/dL, with a difference of less than or equal to 1.0 g/dL between the highest and the lowest values. The last Hb value must be within 10 days prior to randomization.
* Participant has a ferritin level greater than or equal to 30 ng/mL (greater than or equal to 67.4 pmol/L) at screening.
* Participant has a transferrin saturation (TSAT) level greater than or equal to 5% at screening.
* Participant has a serum folate level greater than or equal to lower limit of normal at screening.
* Participant has a serum vitamin B12 level greater than or equal to lower limit of normal at screening.
* Participant's alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels are less than or equal to 3 x upper limit of normal (ULN), and total bilirubin (TBL) is less than or equal to 1.5 x ULN.
* Participant's body weight is 45.0 kg up to a maximum of 160.0 kg.

Exclusion criteria:

* Participant has received any ESA treatment within 12 weeks prior to randomization.
* Participant has had more than one dose of IV iron within 12 weeks prior to randomization.
* Participant has received a RBC transfusion within 8 weeks prior to randomization.
* Participant has a known history of myelodysplastic syndrome or multiple myeloma.
* Participant has a known hereditary hematologic disease such as thalassemia or sickle cell anemia, pure red cell aplasia, or other known causes for anemia other than CKD.
* Participant has a known hemosiderosis, hemochromatosis, coagulation disorder, or hypercoagulable condition.
* Participant has chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosus, rheumatoid arthritis, celiac disease) even if it is currently in remission.
* Participant is anticipated to have elective surgery that is expected to lead to significant blood loss or anticipated elective coronary revascularization.
* Participant has active or chronic gastrointestinal bleeding.
* Participant has received any prior treatment with roxadustat or a hypoxia-inducible factor Prolyl Hydroxylase Inhibitor (HIF-PHI).
* Participant has been treated with iron-chelating agents within 4 weeks prior to randomization.
* Participant has a history of chronic liver disease (e.g., cirrhosis or fibrosis of the liver)
* Participant has a known New York Heart Association Class III or Intravenous (IV) congestive heart failure.
* Participant has had a myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thromboembolic event (e.g., pulmonary embolism) within 12 weeks prior to randomization.
* Uncontrolled hypertension or two or more blood pressure (BP) values of systolic BP (SBP) greater than or equal to 160 mmHg or diastolic BP (DBP) greater than or equal to 95 mmHg confirmed by repeat measurement within 2 weeks prior to randomization.
* Participant has a diagnosis or suspicion (e.g., complex kidney cyst of Bosniak Category 2F or higher) of renal cell carcinoma on renal ultrasound within 12 weeks prior to randomization.
* Participant has a history of malignancy, except the following: cancers determined to be cured or in remission for greater than or equal to 5 years, curatively resected basal cell or squamous cell skin cancers, cervical cancer in situ, or resected colonic polyps.
* Participant is positive for any of the following: Human Immunodeficiency Virus (HIV); hepatitis B surface antigen (HBsAg); or anti-hepatitis C virus antibody (anti-HCV Ab).
* Participant has an active clinically significant infection manifested by White Blood Count (WBC) \> ULN, and/or fever, in conjunction with clinical signs or symptoms of infection within one week prior to randomization.
* Participant has a known untreated proliferative diabetic retinopathy, diabetic macular edema, macular degeneration and retinal vein occlusion.
* Participant has had any prior organ transplant (that has not been explanted) or a scheduled organ transplantation.
* Participant has participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half lives or limit set by national law, whichever is longer, prior to the initiation of Screening.
* Participant has an anticipated use of dapsone in any dose amount or chronic use of acetaminophen (paracetamol) \> 2.0 g/day during the treatment or follow-up period of the study.
* Participant has a history of alcohol or drug abuse within 2 years prior to randomization.

Primary outcomes:
measure: Percentage of Participants With a Hemoglobin (Hb) Response to Treatment at Two Consecutive Visits During the First 24 Weeks of Treatment Without Rescue Therapy Prior to Hb Response
timeFrame: Baseline to week 24
measure: Hb Change From Baseline (BL) to the Average Hb in Weeks 28-52 Regardless of Rescue Therapy
timeFrame: Baseline and weeks 28 to 52
Secondary outcomes:
measure: Hb Change From BL to the Average Hb in Weeks 28-36 Without Having Received Rescue Therapy Within 6 Weeks Prior to and During 8-Week Evaluation Period
timeFrame: Baseline and weeks 28 to 36
measure: Change From BL in Low-Density Lipoprotein (LDL) Cholesterol (Regardless of Fasting Status) to the Average LDL Cholesterol of Weeks 12 to 28
timeFrame: Baseline and weeks 12 to 28
measure: Time to First Use of Rescue Therapy (Composite of Red Blood Cell (RBC) Transfusions, Erythropoiesis-stimulating Agent (ESA) Use, and Intravenous (IV) Iron)
timeFrame: Baseline to week 104 (End of Treatment [EOT])
measure: Change From BL in Short Form (SF)-36 Vitality (VT) Sub-score to the Average VT Sub-score of Weeks 12 to 28
timeFrame: Baseline and weeks 12 to 28
measure: Change From BL in SF-36 Physical Functioning (PF) Sub-score to the Average PF Sub-score of Weeks 12 to 28
timeFrame: Baseline and weeks 12 to 28
measure: Change From BL in Mean Arterial Pressure (MAP) to the Average MAP of Weeks 20 to 28
timeFrame: Baseline and weeks 20 to 28
measure: Time to First Occurrence of Hypertension
timeFrame: Baseline and year 0.5, year 1, year 1.5 and year 2
measure: Rate of Progression of CKD Measured by Annualized Estimated Glomerular Filtration Rate (eGFR) Slope Over Time
timeFrame: Baseline to week 108
measure: Average Level of Hb Over Weeks 28 to 36 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period
timeFrame: Weeks 28 to 36
measure: Average Level of Hb Over Weeks 44 to 52 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period
timeFrame: Weeks 44 to 52
measure: Average Level of Hb Over Weeks 96 to 104 Without Use of Rescue Therapy Within 6 Weeks Prior to and During the Evaluation Period
timeFrame: Weeks 96 to 104
measure: Time to Achieve the First Hb Response Without Rescue Therapy, as Defined by Primary Endpoint
timeFrame: Baseline to week 24
measure: Hb Change From BL to Each Post-Dosing Time Point
timeFrame: Baseline (day 1) and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104
measure: Hb Change From BL to the Average Hb Value of Weeks 28-36 Regardless of the Use of Rescue Therapy
timeFrame: Baseline and weeks 28 to 36
measure: Hb Change From BL to the Average Hb Value of Weeks 44-52 Regardless of the Use of Rescue Therapy
timeFrame: Baseline and weeks 44 to 52
measure: Hb Change From BL to the Average Hb Value of Weeks 96-104 Regardless of the Use of Rescue Therapy
timeFrame: Baseline and weeks 96 to 104
measure: Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 28-36 Without Use of Rescue Therapy
timeFrame: Baseline and weeks 28 to 36
measure: Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 44-52 Without Use of Rescue Therapy
timeFrame: Baseline and weeks 44 to 52
measure: Percentage of Hb Values Within 10.0-12.0 g/dL in Weeks 96-104 Without Use of Rescue Therapy
timeFrame: Baseline and weeks 96 to 104
measure: Time to First Hospitalization
timeFrame: Baseline to week 104
measure: Number of Days of Hospitalization Per Patient Exposure Year (PEY)
timeFrame: Baseline to week 104
measure: Time to First Use of Rescue Therapy (Composite of RBC, Transfusions, ESA Use, and IV Iron) in the First 24 Weeks of Treatment
timeFrame: Baseline to week 24
measure: Time to First Use of RBC Transfusions
timeFrame: Baseline to week 104
measure: Mean Monthly Number of RBC Packs
timeFrame: Baseline to week 104
measure: Mean Monthly Volume of Blood Transfused
timeFrame: Baseline to week 104
measure: Time to First Use of ESA Rescue Therapy
timeFrame: Baseline to week 104
measure: Time to First Use of IV Iron
timeFrame: Baseline to week 104
measure: Change From BL to Each Post-Dosing Visit in Total Cholesterol
timeFrame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104
measure: Change From BL to Each Post-Dosing Visit in Low Density Lipoprotein (LDL)/High-Density Lipoprotein (HDL) Ratio
timeFrame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104
measure: Change From BL to Each Post-Dosing Visit in Non-HDL Cholesterol
timeFrame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104
measure: Change From BL to Each Post-Dosing Visit in Apolipoproteins A1 (ApoA1)
timeFrame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104
measure: Change From BL to Each Post-Dosing Visit in Apolipoproteins B (ApoB)
timeFrame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104
measure: Change From BL to Each Post-Dosing Visit in Ratio ApoB/ApoA1
timeFrame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 68, 84, 104
measure: Percentage of Participants With Mean LDL Cholesterol <100 mg/dL Calculated Over Weeks 12 to 28
timeFrame: Weeks 12 to 28
measure: Percentage of Participants Who Have Achieved Antihypertensive Treatment Goal in CKD Participants Over Weeks 12-28
timeFrame: Weeks 12 to 28
measure: Change From BL to the Average Value of Weeks 12-28 in Quality of Life (QoL) SF-36 Physical Component Score (PCS)
timeFrame: Baseline and weeks 12 to 28
measure: Change From BL to the Average Value of Weeks 12-28 in Anemia Subscale (Ans) of Functional Assessment of Cancer Therapy (FACT-An) Score
timeFrame: Baseline and weeks 12 to 28
measure: Change From BL to the Average Value of Weeks 12-28 in Total FACT-An Score
timeFrame: Baseline and weeks 12 to 28
measure: Change From BL to the Average Value of Weeks 12-28 in the Euroqol Questionnaire - 5 Dimensions 5 Levels (EQ-5D 5L) Visual Analogue Scale (VAS) Score
timeFrame: Baseline and weeks 12 to 28
measure: Change From BL to the Average Value of Weeks 12-28 in Overall Work Impairment Due to Anaemic Symptoms
timeFrame: Baseline and weeks 12 to 28
measure: Percentage of Participants in Each Category in Patients' Global Impression of Change (PGIC)
timeFrame: Week 12 to 28
measure: Change From BL to Each Study Visit in Serum Hepcidin
timeFrame: Baseline and weeks 4,12,20,36,52,104
measure: Change From BL to Each Study Visit in Serum Ferritin
timeFrame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104
measure: Change From BL to Each Study Visit in Serum Transferrin Saturation (TSAT)
timeFrame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104
measure: Change From BL to Each Study Visit in Serum HbA1c Level
timeFrame: Baseline and weeks 12, 28, 36, 44, 60, 84, 104
measure: Change From BL to Each Study Visit in Fasting Blood Glucose
timeFrame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104
measure: Change From BL to Each Study Visit in Albumin/Creatinine Ratio in Urine
timeFrame: Baseline and weeks 12, 24, 36, 52, 64, 76, 88, 104
measure: Change From BL to Each Study Visit in Serum Creatinine (Cr) Ratio
timeFrame: Baseline and weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, 100, 104
measure: Time to Doubling of Serum Creatinine or Chronic Dialysis or Renal Transplant Compared to Baseline
timeFrame: Baseline and year 0.5, year 1, year 1.5 and year 2
measure: Time to CKD Progression (Composite of Doubling Serum Creatinine, Chronic Dialysis or Renal Transplant, and Death)
timeFrame: Baseline and year 0.5, year 1, year 1.5 and year 2
measure: Time to at Least 40% Decrease in eGFR From Baseline, Chronic Dialysis or Renal Transplant
timeFrame: Baseline and year 0.5, year 1, year 1.5 and year 2
Other outcomes:
Locations:
city: Brest
country: Belarus
facility: Site BY37503
city: Gomel
country: Belarus
facility: Site BY37504
city: Grodno
country: Belarus
facility: Site BY37501
city: Minsk
country: Belarus
facility: Site BY37506
city: Minsk
country: Belarus
facility: Site BY37507
city: Minsk
country: Belarus
facility: Site BY37505
city: Vitebsk
country: Belarus
facility: Site BY37502
city: Brussels
country: Belgium
facility: Site BE32004
state: Flemish Brabant
city: Antwerp
country: Belgium
facility: Site BE32002
city: Baudour
country: Belgium
facility: Site BE32012
city: Bonheiden
country: Belgium
facility: Site BE32017
city: Ieper
country: Belgium
facility: Site BE32014
city: Liege
country: Belgium
facility: Site BE32013
city: Pazardjik
country: Bulgaria
facility: Site BG35923
city: Sofia
country: Bulgaria
facility: Site BG35906
city: Sofia
country: Bulgaria
facility: Site BG35908
city: Sofia
country: Bulgaria
facility: Site BG35910
city: Stara Zagora
country: Bulgaria
facility: Site BG35907
city: Varna
country: Bulgaria
facility: Site BG35916
city: Veliko Tarnovo
country: Bulgaria
facility: Site BG35903
city: Barranquilla
country: Colombia
facility: Site CO57007
city: Barranquilla
country: Colombia
facility: Site CO57008
city: Pereira
country: Colombia
facility: Site CO57002
city: La Fe Santo Domingo
country: Dominican Republic
facility: Site DO17101
city: Santiago de los Caballeros
country: Dominican Republic
facility: Site DO17102
city: Santo Domingo
country: Dominican Republic
facility: Site DO17104
city: Santo Domingo
country: Dominican Republic
facility: Site DO17103
city: Tallinn
country: Estonia
facility: Site EE37201
city: Tbilisi
country: Georgia
facility: Site GE99503
city: Tbilisi
country: Georgia
facility: Site GE99504
city: Tbilisi
country: Georgia
facility: Site GE99502
city: Heraklion
country: Greece
facility: Site GR30003
city: Patras
country: Greece
facility: Site GR30002
city: Thessaloniki
country: Greece
facility: Site GR30001
city: Chiquimula
country: Guatemala
facility: Site GT50209
city: Ciudad de Guatemala
country: Guatemala
facility: Site GT50202
city: Ciudad de Guatemala
country: Guatemala
facility: Site GT50208
city: Ciudad de Guatemala
country: Guatemala
facility: Site GT50207
city: Ciudad de Guatemala
country: Guatemala
facility: Site GT50201
city: Guatemala
country: Guatemala
facility: Site GT50205
city: Guatemala
country: Guatemala
facility: Site GT50206
city: Guatemala
country: Guatemala
facility: Site GT50203
city: Budapest
country: Hungary
facility: Site HU36029
city: Gyor
country: Hungary
facility: Site HU36025
city: Kaposvar
country: Hungary
facility: Site HU36026
city: Kistarcsa
country: Hungary
facility: Site HU36027
city: Pecs
country: Hungary
facility: Site HU36008
city: Szent
country: Hungary
facility: Site HU36028
city: Zalsaegerszeg
country: Hungary
facility: Site HU36003
city: Bari
country: Italy
facility: Site IT39001
city: Lecco
country: Italy
facility: Site IT39008
city: Milano
country: Italy
facility: Site IT39006
city: Modena
country: Italy
facility: Site IT39037
city: Pavia
country: Italy
facility: Site IT39036
city: Ciudad de Colon
country: Panama
facility: Site PA50703
city: Ciudad de Panama
country: Panama
facility: Site PA50701
city: Iquitos
country: Peru
facility: Site PE51001
city: Trujillo
country: Peru
facility: Site PE51002
city: Krakow
country: Poland
facility: Site PL48001
state: Malopolska
city: Katowice
country: Poland
facility: Site PL48002
city: Lodz
country: Poland
facility: Site PL48012
city: Lodz
country: Poland
facility: Site PL48008
city: Nowy Tomyśl
country: Poland
facility: Site PL48057
city: Szczecin
country: Poland
facility: Site PL48013
city: Tarnow
country: Poland
facility: Site PL48007
city: Warszawa
country: Poland
facility: Site PL48005
city: Warszawa
country: Poland
facility: Site PL48004
city: Wroclaw
country: Poland
facility: Site PL48006
city: Zamosc
country: Poland
facility: Site PL48014
city: Timisoara
country: Romania
facility: Site RO40005
state: Timis
city: Brasov
country: Romania
facility: Site RO40001
city: Bucharest
country: Romania
facility: Site RO40021
city: Bucuresti
country: Romania
facility: Site RO40012
city: Bucuresti
country: Romania
facility: Site RO40003
city: Oradea
country: Romania
facility: Site RO40004
city: Chelyabinsk
country: Russian Federation
facility: Site RU70024
city: Irkutsk
country: Russian Federation
facility: Site RU70054
city: Kaluga
country: Russian Federation
facility: Site RU70008
city: Moscow
country: Russian Federation
facility: Site RU70051
city: Moscow
country: Russian Federation
facility: Site RU70007
city: Moscow
country: Russian Federation
facility: Site RU70005
city: Moscow
country: Russian Federation
facility: Site RU70048
city: Moscow
country: Russian Federation
facility: Site RU70047
city: Nizhny Novgorod
country: Russian Federation
facility: Site RU70003
city: Omsk
country: Russian Federation
facility: Site RU70004
city: Petrozavodsk
country: Russian Federation
facility: Site RU70043
city: Rostov-on-don
country: Russian Federation
facility: Site RU70014
city: Saint Petersburg
country: Russian Federation
facility: Site RU70022
city: Saint Petersburg
country: Russian Federation
facility: Site RU70011
city: Saint Petersburg
country: Russian Federation
facility: Site RU70002
city: Saint-Petersburg
country: Russian Federation
facility: Site RU70045
city: Saratov
country: Russian Federation
facility: Site RU70060
city: Smolensk
country: Russian Federation
facility: Site RU70006
city: Yaroslavl
country: Russian Federation
facility: Site RU70057
city: Yaroslavl
country: Russian Federation
facility: Site RU70001
city: Belgrade
country: Serbia
facility: Site RS38102
city: Belgrade
country: Serbia
facility: Site RS38104
city: Belgrade
country: Serbia
facility: Site RS38105
city: Belgrade
country: Serbia
facility: Site RS38103
city: Krusevac
country: Serbia
facility: Site RS38117
city: Nis
country: Serbia
facility: Site RS38101
city: Zrenjanin
country: Serbia
facility: Site RS38116
city: Observatory
country: South Africa
facility: Site ZA27001
state: Cape Town
city: Bloemfontein
country: South Africa
facility: Site ZA27004
state: Free State
city: Durban
country: South Africa
facility: Site ZA27002
state: Kwa Zulu Natal
city: Durban
country: South Africa
facility: Site ZA27008
city: Parow
country: South Africa
facility: Site ZA27006
city: Port Elizabeth
country: South Africa
facility: Site ZA27007
city: Alcorcon
country: Spain
facility: Site ES34010
state: Madrid
city: Galdakao
country: Spain
facility: Site ES34011
state: Vizcaya
city: Badalona-Barcelona
country: Spain
facility: Site ES34002
city: Barcelona
country: Spain
facility: Site ES34003
city: Barcelona
country: Spain
facility: Site ES34006
city: Ciudad Real
country: Spain
facility: Site ES34007
city: Ankara
country: Turkey
facility: Site TR90003
city: Edirne
country: Turkey
facility: Site TR90016
city: Kocaeli
country: Turkey
facility: Site TR90024
city: Malatya
country: Turkey
facility: Site TR90020
city: Lviv
country: Ukraine
facility: Site UA38009
state: Lvivska
city: Cherkasy
country: Ukraine
facility: Site UA38021
city: Chernivtsi
country: Ukraine
facility: Site UA38003
city: Dnepropetrovsk
country: Ukraine
facility: Site UA38006
city: Ivano-Frankivsk
country: Ukraine
facility: Site UA38016
city: Kharkiv
country: Ukraine
facility: Site UA38011
city: Kherson
country: Ukraine
facility: Site UA38015
city: Kyiv
country: Ukraine
facility: Site UA38010
city: Kyiv
country: Ukraine
facility: Site UA38012
city: Kyiv
country: Ukraine
facility: Site UA38017
city: Mykolaiv
country: Ukraine
facility: Site UA38007
city: Odessa
country: Ukraine
facility: Site UA38008
city: Odessa
country: Ukraine
facility: Site UA38019
city: Ternopil
country: Ukraine
facility: Site UA38001
city: Uzhgorod
country: Ukraine
facility: Site UA38018
city: Zaporizhzhya
country: Ukraine
facility: Site UA38002
city: Cambridge
country: United Kingdom
facility: Site GB44008
city: Swansea
country: United Kingdom
facility: Site GB44001
city: Welwyn Garden City
country: United Kingdom
facility: Site GB44005
city: Westcliff-on-Sea
country: United Kingdom
facility: Site GB44004
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Medical Monitor
role: STUDY_CHAIR
References:
citation: 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.
citation: Provenzano R, Szczech L, Leong R, Saikali KG, Zhong M, Lee TT, Little DJ, Houser MT, Frison L, Houghton J, Neff TB. Efficacy and Cardiovascular Safety of Roxadustat for Treatment of Anemia in Patients with Non-Dialysis-Dependent CKD: Pooled Results of Three Randomized Clinical Trials. Clin J Am Soc Nephrol. 2021 Aug;16(8):1190-1200. doi: 10.2215/CJN.16191020.