TABLE 1.
Characteristics of included studies.
| Source | Country | NCT number | Setting | Intervention | Type of patients | Duration | Iron therapy | No. of patients (M/F) | Mean age, years |
|---|---|---|---|---|---|---|---|---|---|
| Akizawa T et al. (2020) | Japan | 02969655 | Phase 3, randomized, double-blind, active-controlled, parallel-group | T: Daprodustat (started with 4 mg and adjusted every 4 weeks within the range of 1–24 mg) once daily for 52 weeks | DD-CKD | 52 weeks | Oral or IV | T: 136 (91/45) | T: 64 ± 10a |
| C: rhEPO (Darbepoetin alfa: started at a corresponding dose to the prior rhEPO and then adjusted every 2 weeks within the range of 10–60 μg) IV once weekly | C: 135 (89/46) | C: 64 ± 11a | |||||||
| Holdstock L et al. (2016) | 6 countries (United States, Canada | 01587924 | Phase 2, randomized, triple-blind, active-controlled, parallel-group, multicenter | T: Daprodustat (0.5, 2 or 5 mg) once daily for 4 weeks | DD-CKD | 4 weeks | Oral | T: 62 (43/19) | T: 55.7 ± 17.4a |
| Germany, Denmark, Norway, Sweden) | C: rhEPO (dose: NA) | C: 20 (16/4) | C: 64.2 ± 12.8a | ||||||
| Holdstock L et al. (2019) | 15 countries | 01977573 | Phase 2, randomized, open-label, active-controlled, parallel-group, multicenter | T: Daprodustat (1, 2 or 4 mg) once daily for 24 weeks | NDD-CKD | 24 weeks | Oral | T: 156 (64/92) | T: 66.5 ± 12.78a |
| C: rhEPO (dose for every participant was determined by the investigator) | C: 79 (33/46) | C: 65.4 ± 13.6a | |||||||
| Meadowcroft A et al. (2019) | 16 countries | 01977482 | Phase 2, randomized, triple-blind (open-label rhEPO), dose-ranging, active-controlled, parallel-group, multicenter | T: Daprodustat (4, 6, 8, 10 or 12 mg) once daily for 24 weeks | DD-CKD | 24 weeks | Oral or IV | T: 171 (108/63) | T: 59.6 ± 13.3a |
| C: Placebo for 4 weeks and then open-label rhEPO (dose for every participant was determined by the investigator to achieve hemoglobin within the target range (10–11.5 g/dl) as required) | C: 39 (26/13) | C: 59.7 ± 18.7a | |||||||
| Nangaku M et al. (2021) | Japan | 02791763 | Phase 3, randomized, open-label, active-controlled, parallel-group, multicenter | T: Daprodustat (1, 2, 4, 6, 8, 12, 18 or 24 mg) once daily for 52 weeks, C: rhEPO (Epoetin beta pegol: started at the dose of 25 μg every 2 weeks for rhEPO-naïve patients and 25–250 μg every 4 weeks for rhEPO users and then adjusted every 4 weeks) | NDD-CKD | 52 weeks | Oral or IV | T: 149 (96/53) | T: 68 ± 12a |
| C: 150 (92/58) | C: 70 ± 9a | ||||||||
| Singh A et al. (2021) | 38 countries | 02876835 | Phase 3, randomized, open-label, active-controlled, parallel-group, multicenter | T: Daprodustat (started between 1 and 4 mg and then adjusted within the range of 1–24 mg) once daily for 52 weeks | NDD-CKD | 52 weeks | Oral or IV | T: 1937 (835/1102) | T: 67 (57–75)b |
| C: rhEPO (Darbepoetin alfa: started based on the patient’s weight and hemoglobin level at the time of randomization for rhEPO-naïve patients or on the previous dose for rhEPO users. Dose stepped changes were predefined, and most steps increased the dose by 25–33%) | C: 1935 (864/1071) | C: 67 (57–74)b | |||||||
| Singh A et al. (2021) | 35 countries | 02879305 | Phase 3, randomized, open-label, active-controlled, parallel-group, multicenter | T: Daprodustat (started between 4 and 12 mg and then adjusted within the range of 1–24 mg) once daily for 52 weeks | DD-CKD | 52 weeks | Oral or IV | T: 1487 (851/636) | T: 58 (48–67)b |
| C: rhEPO (started based on the previous dose and hemoglobin level at the time of randomization. Dose stepped changes were predefined, and most steps increased the dose by 25–33%.) | C: 1477 (847/630) | C: 59 (47–68)b |
Abbreviations: C, control group; CKD, chronic kidney disease; DD, dialysis-dependent; IV, intravenous; M/F, male/female; NCT, national clinical trial; NDD, non-dialysis-dependent; rhEPO, recombinant human erythropoietin; T, treatment group; TIW, three times weekly; aMean±standard deviation.