Table 1.

Characteristics of the included trials.

Reference	Trial phase	Design	Trial drugs	Control	Study population	No. of enrolled subjects		Follow-up (weeks)	Mean age (years)		Primary end point
						Intervention	Control		Intervention	Control
Akizawa et al. [30]	2	Double-blind, placebo-controlled	Daprodustat	Placebo	HD	97	19	8	62.2	63.48	Hb change from baseline (CFB) at week 4
Holdstock et al. [31]	2b	Randomized, controlled, open-label, parallel-group, multicenter	Daprodustat	rhEPO and its analogs	CKD stages 3-5	252	44	28	66.5	65.4	Hb concentration at week 24
Meadowcroft et al. [32]	2b	Randomized, controlled, open-label, parallel-group, multicenter	Daprodustat	Placebo	HD	216	177	28	59.6	59.7	Hb change from baseline at week 4
Holdstock et al. [23]	2a	Randomized, controlled parallel-group, multicenter	Daprodustat	Placebo	CKD stages 3–5	73	19	6	68.3	69.2	Modeled change in Hb from baseline over 4 weeks of treatment
				rhEPO	HD	83	21	6	55.7	64.2
Martin et al. [27]	2a	Multicenter, randomized, double-blind	Vadadustat	Placebo	CKD stages 3-4	191	19	6	65.7	64.9	Mean absolute change in Hb from baseline to the end of treatment
Pergola et al. [20]	2b	Double-blind, randomized, placebo-controlled	Vadadustat	Placebo	nondialysis dependent CKD	138	72	20	66.6	65.9	The percentage of patients achieved or maintained a mean Hb level of 11.0 g/dl or an increase in Hb of 1.2 g/dl over the predose average (average of the 2 Hb values obtained before dosing at screening and baseline) during the last 2 weeks of treatment
Akizawa et al. [25]	2	Randomized, double-blind	Roxadustat	Placebo	non-dialysis-dependent CKD	80	27	24	64.4	61.9	The rate of rise in Hb from baseline to the final assessment in the fixed-dose period (EOF)
Besarab et al. [34]	2a	Single-blind, randomized placebo-controlled dose-ranging and pharmacodynamics	Roxadustat	Placebo	non-dialysis-dependent CKD	88	28	12	65.8	68.6	Maximum Hb change from baseline at any time from baseline to 8 weeks of treatment
Chen et al. [35]	2	Double-blinded	Roxadustat	Placebo	CKD stages 3-5, not on dialysis, with baseline Hb < 10g/dl	61	30	8	49.7	51.4	The percentage of subjects with successful dose conversion defined as a Hb level maintained at no <0.5g/dL below mean baseline value during the last 2 weeks of the 6-week dosing period
		Open-label		Epoetin alfa	HD with Hb 9-12g/dl	74	22	6	50.8	53.8
Chen et al. [22]	3	Randomized, open-label	Roxadustat	Epoetin alfa	HD	305	101	27	47.6	51	Mean change in Hb level from baseline to the average level during weeks 23 through 27
Chen et al. [22]	3	Randomized, double-blind	Roxadustat	Placebo	CKD	154	52	8	54.7	53.2	Mean change from baseline in the Hb level, averaged over weeks 7 through 9
Provenzano et al. [36]	2	Randomized, open-label	Roxadustat	Epoetin alfa	HD	54	13	8	55.8	59.5	The proportion of participants whose Hb levels did not decrease by > 0.5 g/dL from baseline (defined as the mean of the last 3 Hb values obtained prior to the first dose of study treatment)
				Epoetin alfa	HD	90	23	4	56.9	57	The proportion of participants whose mean Hb level was ≥11 g/dL averaged over the last 4 weeks (weeks 16 through 19)
Akizawa et al. [38]	2b	Randomized, double-blind	Enarodustat	Placebo	CKD ESA-naïve patients	94	23	6	NR	65.3	Hb level increase rate per week for the correction group
				Placebo	CKD ESA-treated patients	107	24	6	NR	66.2	The proportion of subjects maintained a change from baseline Hb level within ± 1.0 g/dL at the evaluation point for the conversion group
Akizawa et al. [25]	2b	Randomized, double-blind	Enarodustat	Placebo	HD	121	22	6	NR	60.7	The percentage of subjects with a change in the Hb level within ± 1.0 g/dL from baseline to the evaluation-point
Parmar et al. [24]	2	Multicentric, randomized, double-blind	Desidustat	Placebo	CKD stages 1-4	117	30	6	48.48	46.9	Hb increase in a dose-related manner across all the doses after 6 weeks of treatment
Macdougall et al. [26]	2b	Randomized, double-blind	Molidustat	Placebo	CKD stages 3-5, not on dialysis, ESA-naïve patients, with mean Hb < 10.5g/dl	101	19	12	69	67	The change in Hb level between baseline and the evaluation phase
		Open-label		Darbepoetin	CKD stages 3-5, not no dialysis, stable darbepoetin treated, with mean Hb 9-12g/dl	92	28	12	68	69
		Open-label		Epoetin	On dialysis, stable epoetin treated, mean Hb 9-11.5g/dL	157	39	13	59	59
Akizawa et al. [38]	2b	Controlled, parallel-group, open-label, multicenter	Molidustat	Darbepoetin	Not on dialysis	164	42	52	70	69	The change in blood Hb level from baseline to each post-baseline visit during the main phase of the study
				Epoetin	On dialysis	88	30	52	61	59

HD: hemodialysis; Hb: hemoglobin; rhEPO: recombinant human erythropoietin; CKD: chronic kidney disease; NR: not reported.