| Study characteristics |
| Methods |
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| Participants |
General information
Setting: multicentre (number of sites not reported) Country: international (USA, Argentina, Australia, Austria, Canada, Germany, India, Italy, Korea, Malaysia, Mexico, Poland, Russian Federation, South Africa, Spain, UK) Inclusion criteria: aged 18 to 99 years; planning to start chronic dialysis within the next 6 weeks (from the date of the screening visit) OR have started and received dialysis (as specified below) for kidney failure for a maximum of ≤ 90 days immediately prior to randomisation and is not expected to stop dialysis during the duration of the trial: HD ≥ 2 times/week or PD ≥ 4 times/week including incremental schedule; subjects on CAPD and APD; Hb 8 to 10.5 g/dL at screening and 8 to 11.0 g/dL at randomisation; capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol Exclusion criteria: planned living‐related or living‐unrelated kidney transplant during the study; ferritin ≤ 100 (ng/mL) at screening or after IV iron supplementation; TSAT ≤ 20% at screening or after IV iron supplementation; vitamin B12 (cobalamin) < LLN at screening or after vitamin B12 supplementation; folate < 2.0 ng/mL at screening; history of bone marrow aplasia or PRCA; untreated pernicious anaemia, thalassaemia major, sickle cell disease, or myelodysplastic syndrome; evidence of actively bleeding gastric, duodenal, or oesophageal ulcer disease or clinically significant GI bleeding ≤ 10 weeks prior to screening through to randomisation (day 1); use of any ESA treatment within 8 weeks prior to screening except for limited use as part of dialysis initiation; MI or acute coronary syndrome: ≤ 10 weeks prior to screening through to randomisation (day 1); stroke or TIA: ≤ 10 weeks prior to screening through to randomisation (day 1); chronic NYHA class IV HF; current uncontrolled hypertension as determined by the Investigator that would contraindicate the use of rHuEPO; QTcB (day 1) > 500 msec, or QTcB >530 msec in subjects with bundle branch block; ALT >2 times ULN (screening only); bilirubin > 1.5 times ULN (screening only); current unstable liver or biliary disease per investigator assessment, generally defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice, or cirrhosis; history of malignancy within the 2 years prior to screening through to randomisation (day 1), or currently receiving treatment for cancer, or complex kidney cyst > 3 cm; use of other investigational agent or device prior to screening through to randomisation (day 1); pregnant, breastfeeding, or does not agree to follow one of the contraceptive options; 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 (example intolerance to rHuEPO) or prevent understanding of the aims or investigational procedures or possible consequences of the study Target Hb: 10 to 11 g/dL
Baseline characteristics
CKD stage: HD and PD Number (randomised/analysed): treatment group (157/155); control group (155/151) Mean age (years): treatment group (53.7); control group (55.8) Sex (M, %): not reported Time on dialysis: not reported eGFR: not reported
Comorbidities
CV disease: not reported Heart disease: not reported Hypertension: not reported Diabetes (number, %): not reported -
Prior agents used (number, %)
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| Interventions |
Treatment group
Daprodustat (oral): 1, 2, 4, 6, 8, 10, 12, 16, 24 mg/day
Control group
Co‐interventions
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| Outcomes |
Primary outcome
Secondary outcomes
Average monthly IV iron dose mg/subject from baseline to week 52 Change from baseline in SBP, DBP and MAP to week 52 Number of BP exacerbation events/100 patient years to week 58 Number (%) of subjects with at least one BP exacerbation event during study up to week 58 Change from baseline in Hb up to week 52 Number (%) of Hb responders week 28 to week 52 Percentage time for which Hb is in analysis range week 28 to week 52 Time to rescue up to week 52 Change in SF‐36 HRQoL) scores up to week 52 Change from baseline in EQ‐5D‐5L questionnaire score at week 52 Change from baseline in EQ‐5D‐5L VAS at week 52 Change from baseline in the CKD‐Anemia Symptoms Questionnaire at week 52 Change from baseline in patient PGI‐S up to week 52 Summary of pharmacokinetic parameters of plasma daprodustat and three major metabolites in dialysis subjects: predose, 0.5, 1, 2, and 3 hours post dose at week 4, 8 or 12
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| Notes |
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| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
Sequence generation methods were not reported in sufficient detail to permit judgement |
| Allocation concealment (selection bias) |
Unclear risk |
Method of allocation concealment was not reported in sufficient detail to permit judgement |
| Blinding of participants and personnel (performance bias)
All outcomes |
High risk |
Quote: "Open label" |
| Blinding of outcome assessment (detection bias)
All outcomes |
High risk |
Objective and subjective outcomes were reported |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
Quote: "Overall 99% (155/157) pts on Dapro and 97% (151/155) on Darbe completed the study"
Loss to follow‐up: < 5% |
| Selective reporting (reporting bias) |
High risk |
Clinically‐relevant outcomes that would be expected for this type of intervention were not reported |
| Other bias |
High risk |
Baseline characteristics, or different non‐randomised co‐interventions were not reported between groups
Funder was likely to influence data analysis and study reporting or interpretation
Conflicts of interest were not reported |
