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. 2025 Feb 25;35(2):129–167. doi: 10.25259/ijn_389_23

Table 35:

Evidence profile for vadadustat as an alternative to ESA in DD-CKD patients

Population: Anemia in dialysis-dependent chronic kidney disease

Intervention: Vadadustat

Comparator: Darbepoetin alpha

Outcome

Time frame

Study results and measurements Absolute effect estimates

Certainty of the evidence

Plain language summary
Darbepoetin alpha Vadadustat
Need for iron supplementation No studies were found that viewed the need for iron supplementation.
All-cause mortality up to 116 weeks

Odds ratio: 1.00

(CI 95% 0.83–1.21)

Based on data from 3902 participants in one study

129

per 1000

129

per 1000

Very low

Due to very serious risk of bias, due to serious imprecision1

We are uncertain whether vadadustat has little or no difference on all-cause mortality up to 116 weeks.

Difference: 0 fewer per 1000

(CI 95% 20 fewer–23 more)

All-cause mortality up to 52 weeks

Odds ratio: 2.00

(CI 95% 0.18–22.28)

Based on data from 323 participants in one study

6

per 1000

11

per 1000

Very low

Due to serious risk of bias, due to very serious imprecision, due to serious indirectness2

We are uncertain whether vadadustat increases all-cause mortality up to 52 weeks.

Difference: 6 more per 1000

(CI 95% 5 fewer–113 more)

Need for ESA in incident dialysis group up to 116 weeks

Odds ratio: 1.75

(CI 95% 0.83–3.71)

Based on data from 265 participants in one study

93

per 1000

152

per 1000

Very low

Due to very serious risk of bias, due to serious indirectness, due to very serious imprecision3

We are uncertain whether vadadustat increases the need for ESA in an incident dialysis group up to 116 weeks.

Difference: 59 more per 1000

(CI 95% 15 fewer–183 more)

Incidences of MACE up to 116 weeks Odds ratio: 0.93 (CI 95% 0.79–1.10) Based on data from 3902 participants in one study

193

per 1000

181

per 1000

Very low

Due to very serious risk of bias, due to serious imprecision4

We are uncertain whether vadadustat decreases incidences of MACE up to 116 weeks.
Difference: 11 fewer per 1000 (CI 95% 34 fewer–15 more)
Need for ESA in prevalent dialysis group up to 116 weeks Odds ratio: 1.25 (CI 95% 1.03–1.51) Based on data from 2792 participants in one study 175 per 1000 209 per 1000 Low Due to very serious risk of bias5 Vadadustat may increase need for ESA in prevalent dialysis group up to 116 weeks.

Difference: 35 more per 1000

(CI 95% 4 more–68 more)

Any adverse event in incident dialysis group up to 116 weeks

Odds ratio: 0.88

(CI 95% 0.50–1.55)

Based on data from 365 participants in one study

855

per 1000

838

per 1000

Very low

Due to very serious risk of bias, due to very serious imprecision6

We are uncertain whether vadadustat decreases any adverse events in an incident dialysis group up to 116 weeks.

Difference: 17 fewer per 1000

(CI 95% 108 fewer–46 more)

Any adverse event in prevalent dialysis group up to 116 weeks

Odds ratio: 0.91

(CI 95% 0.74–1.12)

Based on data from 3537 participants in one study

893

per 1000

883

per 1000

Very low

Due to very serious risk of bias, due to serious imprecision7

We are uncertain whether vadadustat decreases any adverse event in prevalent dialysis group up to 116 weeks.

Difference: 9 fewer per 1000

(CI 95% 32 fewer–10 more)

Adverse event up to 52 weeks Odds ratio: 0.37 (CI 95% 0.10–1.40) Based on data from 323 participants in one study

981

per 1000

950

per 1000

Very low

Due to serious risk of bias, due to serious indirectness, due to serious imprecision8

We are uncertain whether vadadustat decreases any adverse event up to 52 weeks.
Difference: 31 fewer per 1000 (CI 95% 143 fewer–5 more)
Incidence of MACE plus up to 116 weeks

Odds ratio: 0.92

(CI 95% 0.79–1.07)

Based on data from 3902 participants in one study

230

per 1000

215

per 1000

Very low

Due to very serious risk of bias, due to serious imprecision9

We are uncertain whether vadadustat decreases incidence of MACE plus (expanded MACE) up to 116 weeks.

Difference: 14 fewer per 1000

(CI 95% 39 fewer–12 more)

Change in hemoglobin levels from baseline up to 52 weeks

Measured by:

Scale: High better

Based on data from 4243 participants in three studies

Mean

Mean

Low

Due to very serious risk of bias10

Vadadustat may decrease hemoglobin levels from baseline up to 52 weeks.

Difference: 0.15 lower (MD)

(CI 95% 0.24 lower–0.07 lower)

QoL No studies were found that viewed QoL.
Fatigue No studies were found that viewed fatigue.

Risk of Bias: very serious. Inadequate concealment of allocation during randomization process, resulting in potential for selection bias, inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias, missing intention-to-treat analysis; Imprecision: serious. The 95% CI of the included study overlaps line of no effect (i.e., CI includes 1.0) rate, wide confidence intervals; Publication bias: not serious. Mostly commercially funded studies. Risk of Bias: serious. Missing intention-to-treat analysis; Indirectness: serious. The included study was from non-South Asian countries and was downgraded for lack of directness by one level; Imprecision: very serious. Due to less events (< 400) and inadequate optimal information size (OIS), the 95% CI of the included study overlaps line of no effect, wide confidence intervals; Publication bias: not serious. Mostly commercially funded studies. Risk of Bias: very serious. Missing intention-to-treat analysis; inadequate concealment of allocation during randomization process, resulting in potential for selection bias, inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias; Indirectness: serious. The included study was from non-South Asian countries and was downgraded for lack of directness by one level; Imprecision: very serious. Due to less events (< 400) and inadequate optimal information size (OIS), the 95% CI of the included study overlaps line of no effect, wide confidence intervals; Publication bias: not serious. Mostly commercially funded studies. Risk of Bias: very serious. Missing intention-to-treat analysis, inadequate concealment of allocation during randomization process, resulting in potential for selection bias, inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias; Imprecision: serious. Only data from one study, the 95% CI of the included study overlaps line of no effect (i.e., CI includes 1.0) rate; Publication bias: not serious. Mostly commercially funded studies. Risk of Bias: very serious. Inadequate concealment of allocation during randomization process, resulting in potential for selection bias, inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias; missing intention-to-treat analysis; Publication bias: not serious. Mostly commercially funded studies. Risk of Bias: very serious. Inadequate concealment of allocation during randomization process, resulting in potential for selection bias, inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias; missing intention-to-treat analysis; Imprecision: very serious. Due to less events (< 400) and inadequate optimal information size (OIS), the 95% CI of the included study overlaps line of no effect (i.e., CI includes 1.0) rate, wide confidence intervals; Publication bias: not serious. Mostly commercially funded studies. Risk of Bias: very serious. Inadequate concealment of allocation during randomization process, resulting in potential for selection bias, inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias; missing intention-to-treat analysis; Imprecision: serious. The 95% CI of the included study overlaps line of no effect (i.e., CI includes 1.0) rate, wide confidence intervals; Publication bias: not serious. Mostly commercially funded studies. Risk of Bias: serious. Missing intention-to-treat analysis; Indirectness: serious. The included study was from non-South Asian country and was downgraded for lack of directness by one level; Imprecision: serious. Due to less events (< 400) and inadequate optimal information size (OIS), wide confidence intervals, the 95% CI of the included study overlaps line of no effect (i.e. CI includes 1.0) rate; Publication bias: not serious. Mostly commercially funded studies. Risk of Bias: very serious. Missing intention-to-treat analysis, inadequate concealment of allocation during randomization process, resulting in potential for selection bias, inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias; Imprecision: serious. The 95% CI of the included study overlaps line of no effect (i.e., CI includes 1.0) rate; Publication bias: not serious. Mostly commercially funded studies. Risk of Bias: very serious. Missing intention-to-treat analysis; inadequate concealment of allocation during randomization process, resulting in potential for selection bias, inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias; Publication bias: not serious. Mostly commercially funded studies. DD: Dialysis-Dependent, CKD: Chronic kidney disease, ESA: Eythropoiesis-stimulating agents, MACE: Major adverse cardiovascular events, QoL: Quality of life, GDG: Guideline development group, CI: Confidence interval