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