| Inclusion criteria . | Exclusion criteria . |
|---|---|
Age: 18–≤99 years of ageCKD stage (at screening): KDOQI CKD Stages 3, 4 or 5 defined by eGFR using the CKD Epidemiology Collaboration (CKD-EPI) formula ESAs: ● Group 1 (not using ESAs): No ESA use within the 6 weeks prior to screening and no ESA use between screening and randomization (Day 1) ● Group 2 (ESA users): Use of any approved ESA for the 6 weeks prior to screening and continuing between screening and randomization Hb concentrationa:On Week –8:● Group 1 (not using ESAs): 8–10 g/dL● Group 2 (ESA users): 8–12 g/dL On randomization (Day 1):● Group 1 (not using ESAs): 8–10 g/dL | Dialysis: On dialysis or clinical evidence of impending need to initiate dialysis within 90 days after study start (Day 1) Kidney transplant: Planned living kidney transplant within 52 weeks after study start (Day 1) Iron: Ferritin ≤100 ng/mL (≤100 µg/L), TSAT ≤20%, at screening Evidence of non-renal anaemia: Aplasias, untreated pernicious anaemia, thalassemia major, sickle cell disease or myelodysplastic syndrome, GI bleeding Cardiovascular comorbidities: MI or acute coronary syndrome or stroke or TIA ≤4 weeks of screening, NYHA Class IV heart failure, uncontrolled hypertension (contraindicating rhEPO use) Liver disease (any one of the following): ● Alanine transaminase: >2× ULN at screening ● Bilirubin: >1.5× ULN at screening ● Current unstable liver or biliary disease per investigator assessment |
● Group 2 (ESA users): Hb 8–11 g/dL and receiving at least the minimum rhEPO dose [epoetins (including biosimilars): 1500 U/week IV or 1000 U/week SC; darbepoetin alfa: 20 µg/4 weeks SC/IV; methoxy PEG- epoetin: 30 µg/month SC/IV] Compliance with placebo [randomization (Day 1) only]: ≥80% and ≤120% compliance with placebo during run-in period | Malignancy: History of malignancy within 2 years before screening through to randomization (Day 1) or currently receiving treatment for cancer or complex kidney cyst Females only: Pregnancy (as confirmed by a positive serum human chorionic gonadotrophin test), breastfeeding, or subject is of reproductive potential and does not agree to follow one of the contraceptive options listed in the List of Highly Effective Methods for Avoiding Pregnancy Other conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the subject at unacceptable risk, which may affect study compliance (e.g. intolerance to darbepoetin alfa) or prevent understanding of the aims or investigational procedures or possible consequences of the study |
| Inclusion criteria . | Exclusion criteria . |
|---|---|
Age: 18–≤99 years of ageCKD stage (at screening): KDOQI CKD Stages 3, 4 or 5 defined by eGFR using the CKD Epidemiology Collaboration (CKD-EPI) formula ESAs: ● Group 1 (not using ESAs): No ESA use within the 6 weeks prior to screening and no ESA use between screening and randomization (Day 1) ● Group 2 (ESA users): Use of any approved ESA for the 6 weeks prior to screening and continuing between screening and randomization Hb concentrationa:On Week –8:● Group 1 (not using ESAs): 8–10 g/dL● Group 2 (ESA users): 8–12 g/dL On randomization (Day 1):● Group 1 (not using ESAs): 8–10 g/dL | Dialysis: On dialysis or clinical evidence of impending need to initiate dialysis within 90 days after study start (Day 1) Kidney transplant: Planned living kidney transplant within 52 weeks after study start (Day 1) Iron: Ferritin ≤100 ng/mL (≤100 µg/L), TSAT ≤20%, at screening Evidence of non-renal anaemia: Aplasias, untreated pernicious anaemia, thalassemia major, sickle cell disease or myelodysplastic syndrome, GI bleeding Cardiovascular comorbidities: MI or acute coronary syndrome or stroke or TIA ≤4 weeks of screening, NYHA Class IV heart failure, uncontrolled hypertension (contraindicating rhEPO use) Liver disease (any one of the following): ● Alanine transaminase: >2× ULN at screening ● Bilirubin: >1.5× ULN at screening ● Current unstable liver or biliary disease per investigator assessment |
● Group 2 (ESA users): Hb 8–11 g/dL and receiving at least the minimum rhEPO dose [epoetins (including biosimilars): 1500 U/week IV or 1000 U/week SC; darbepoetin alfa: 20 µg/4 weeks SC/IV; methoxy PEG- epoetin: 30 µg/month SC/IV] Compliance with placebo [randomization (Day 1) only]: ≥80% and ≤120% compliance with placebo during run-in period | Malignancy: History of malignancy within 2 years before screening through to randomization (Day 1) or currently receiving treatment for cancer or complex kidney cyst Females only: Pregnancy (as confirmed by a positive serum human chorionic gonadotrophin test), breastfeeding, or subject is of reproductive potential and does not agree to follow one of the contraceptive options listed in the List of Highly Effective Methods for Avoiding Pregnancy Other conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the subject at unacceptable risk, which may affect study compliance (e.g. intolerance to darbepoetin alfa) or prevent understanding of the aims or investigational procedures or possible consequences of the study |
CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; ESA, erythropoiesis-stimulating agent; GI, gastrointestinal; IV, intravenous; Hb, haemoglobin; HD, haemodialysis; KDOQI, Kidney Disease Outcomes Quality Initiative; MI, myocardial infarction; NYHA, New York Heart Association; PD, peritoneal dialysis; PEG, polyethylene glycol; rhEPO, recombinant human erythropoietin; SC, subcutaneous; TIA, transient ischaemic attack; TSAT, transferrin saturation; ULN, upper limit of normal.
Determined using HemoCue, a point-of-care test.
Note: Ophthalmological exclusions were not included given that completed studies with daprodustat did not identify any clinically meaningful changes in proliferative retinopathy, macular oedema, or choroidal neovascularization with daprodustat [15, 29].
| Inclusion criteria . | Exclusion criteria . |
|---|---|
Age: 18–≤99 years of ageCKD stage (at screening): KDOQI CKD Stages 3, 4 or 5 defined by eGFR using the CKD Epidemiology Collaboration (CKD-EPI) formula ESAs: ● Group 1 (not using ESAs): No ESA use within the 6 weeks prior to screening and no ESA use between screening and randomization (Day 1) ● Group 2 (ESA users): Use of any approved ESA for the 6 weeks prior to screening and continuing between screening and randomization Hb concentrationa:On Week –8:● Group 1 (not using ESAs): 8–10 g/dL● Group 2 (ESA users): 8–12 g/dL On randomization (Day 1):● Group 1 (not using ESAs): 8–10 g/dL | Dialysis: On dialysis or clinical evidence of impending need to initiate dialysis within 90 days after study start (Day 1) Kidney transplant: Planned living kidney transplant within 52 weeks after study start (Day 1) Iron: Ferritin ≤100 ng/mL (≤100 µg/L), TSAT ≤20%, at screening Evidence of non-renal anaemia: Aplasias, untreated pernicious anaemia, thalassemia major, sickle cell disease or myelodysplastic syndrome, GI bleeding Cardiovascular comorbidities: MI or acute coronary syndrome or stroke or TIA ≤4 weeks of screening, NYHA Class IV heart failure, uncontrolled hypertension (contraindicating rhEPO use) Liver disease (any one of the following): ● Alanine transaminase: >2× ULN at screening ● Bilirubin: >1.5× ULN at screening ● Current unstable liver or biliary disease per investigator assessment |
● Group 2 (ESA users): Hb 8–11 g/dL and receiving at least the minimum rhEPO dose [epoetins (including biosimilars): 1500 U/week IV or 1000 U/week SC; darbepoetin alfa: 20 µg/4 weeks SC/IV; methoxy PEG- epoetin: 30 µg/month SC/IV] Compliance with placebo [randomization (Day 1) only]: ≥80% and ≤120% compliance with placebo during run-in period | Malignancy: History of malignancy within 2 years before screening through to randomization (Day 1) or currently receiving treatment for cancer or complex kidney cyst Females only: Pregnancy (as confirmed by a positive serum human chorionic gonadotrophin test), breastfeeding, or subject is of reproductive potential and does not agree to follow one of the contraceptive options listed in the List of Highly Effective Methods for Avoiding Pregnancy Other conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the subject at unacceptable risk, which may affect study compliance (e.g. intolerance to darbepoetin alfa) or prevent understanding of the aims or investigational procedures or possible consequences of the study |
| Inclusion criteria . | Exclusion criteria . |
|---|---|
Age: 18–≤99 years of ageCKD stage (at screening): KDOQI CKD Stages 3, 4 or 5 defined by eGFR using the CKD Epidemiology Collaboration (CKD-EPI) formula ESAs: ● Group 1 (not using ESAs): No ESA use within the 6 weeks prior to screening and no ESA use between screening and randomization (Day 1) ● Group 2 (ESA users): Use of any approved ESA for the 6 weeks prior to screening and continuing between screening and randomization Hb concentrationa:On Week –8:● Group 1 (not using ESAs): 8–10 g/dL● Group 2 (ESA users): 8–12 g/dL On randomization (Day 1):● Group 1 (not using ESAs): 8–10 g/dL | Dialysis: On dialysis or clinical evidence of impending need to initiate dialysis within 90 days after study start (Day 1) Kidney transplant: Planned living kidney transplant within 52 weeks after study start (Day 1) Iron: Ferritin ≤100 ng/mL (≤100 µg/L), TSAT ≤20%, at screening Evidence of non-renal anaemia: Aplasias, untreated pernicious anaemia, thalassemia major, sickle cell disease or myelodysplastic syndrome, GI bleeding Cardiovascular comorbidities: MI or acute coronary syndrome or stroke or TIA ≤4 weeks of screening, NYHA Class IV heart failure, uncontrolled hypertension (contraindicating rhEPO use) Liver disease (any one of the following): ● Alanine transaminase: >2× ULN at screening ● Bilirubin: >1.5× ULN at screening ● Current unstable liver or biliary disease per investigator assessment |
● Group 2 (ESA users): Hb 8–11 g/dL and receiving at least the minimum rhEPO dose [epoetins (including biosimilars): 1500 U/week IV or 1000 U/week SC; darbepoetin alfa: 20 µg/4 weeks SC/IV; methoxy PEG- epoetin: 30 µg/month SC/IV] Compliance with placebo [randomization (Day 1) only]: ≥80% and ≤120% compliance with placebo during run-in period | Malignancy: History of malignancy within 2 years before screening through to randomization (Day 1) or currently receiving treatment for cancer or complex kidney cyst Females only: Pregnancy (as confirmed by a positive serum human chorionic gonadotrophin test), breastfeeding, or subject is of reproductive potential and does not agree to follow one of the contraceptive options listed in the List of Highly Effective Methods for Avoiding Pregnancy Other conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the subject at unacceptable risk, which may affect study compliance (e.g. intolerance to darbepoetin alfa) or prevent understanding of the aims or investigational procedures or possible consequences of the study |
CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; ESA, erythropoiesis-stimulating agent; GI, gastrointestinal; IV, intravenous; Hb, haemoglobin; HD, haemodialysis; KDOQI, Kidney Disease Outcomes Quality Initiative; MI, myocardial infarction; NYHA, New York Heart Association; PD, peritoneal dialysis; PEG, polyethylene glycol; rhEPO, recombinant human erythropoietin; SC, subcutaneous; TIA, transient ischaemic attack; TSAT, transferrin saturation; ULN, upper limit of normal.
Determined using HemoCue, a point-of-care test.
Note: Ophthalmological exclusions were not included given that completed studies with daprodustat did not identify any clinically meaningful changes in proliferative retinopathy, macular oedema, or choroidal neovascularization with daprodustat [15, 29].
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