Trial · NCT02680574
Efficacy and Safety Study to Evaluate Vadadustat for the Maintenance Treatment of Anemia in Participants With Non-dialysis-dependent Chronic Kidney Disease (NDD-CKD)
NCT02680574, Phase 3, Completed, Akebia Therapeutics; results first posted 2022-06-27
3 sourcestrials-2026-11-12-0.5.0
Download JSON
Cite this record
ConductScience Library. Efficacy and Safety Study to Evaluate Vadadustat for the Maintenance Treatment of Anemia in Participants With Non-dialysis-dependent Chronic Kidney Disease (NDD-CKD). Trials, record NCT02680574. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT02680574
On this page
Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Efficacy and Safety Study to Evaluate Vadadustat for the Maintenance Treatment of Anemia in Participants With Non-dialysis-dependent Chronic Kidney Disease (NDD-CKD)
- NCT number
- NCT02680574
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 1,725 participants, actual
- Lead sponsor
- Akebia Therapeutics
- Conditions
- Anemia, Non-Dialysis-Dependent Chronic Kidney Disease
- Interventions
- Vadadustat, Darbepoetin alfa
- First posted
- 2016-02-11
- Last updated
- 2022-06-27
- Other registries' IDs
- eudract:2015-004774-14
- Results first posted
- 2022-06-27
Source ClinicalTrials.gov
Registered outcomes17
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36) | Baseline; Weeks 24 to 36 | The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Primary Efficacy Period was calculated as the average Hb value over Weeks 24 to 36. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with Baseline hemoglobin concentration (\<10.0 versus ≥10.0 g/dL), geographic region (United States \[US\] versus European Union \[EU\] versus Rest of World \[ROW\]), and New York Heart Association congestive heart failure (NYHA CHF) class (Class 0 \[no CHF\] or I versus II or III) as covariates. |
| Primary | Median Time to First Major Adverse Cardiovascular Event (MACE) | Up to Week 208 | MACE was defined as all-cause mortality, non-fatal myocardial infarction (MI), or non-fatal stroke. The primary safety outcome was positively adjudicated first MACE, which was defined as any death, Endpoint Adjudication Committee (EAC)-confirmed non-fatal MI, or EAC-confirmed non-fatal stroke occurring between the first dose date and each participant's last participation date. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure. |
| Secondary | Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52) | Baseline; Weeks 40 to 52 | The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Secondary Efficacy Period was calculated as the average Hb value over Weeks 40 to 52. Analysis was conducted using an ANCOVA model with multiple imputation for missing data with Baseline hemoglobin concentration (\<10.0 versus ≥10.0 g/dL), geographic region (US versus EU versus ROW), and NYHA CHF class (Class 0 \[no CHF\] or I versus II or III) as covariates. |
| Secondary | Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis | Up to Week 208 | MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Hospitalization for EAC adjudicated heart failure included presentation of participants to an acute care facility requiring an overnight hospitalization (change in calendar day) with an exacerbation of heart failure requiring treatment. EAC confirmed thromboembolic events for this secondary outcome measure included arterial thrombosis, deep vein thrombosis, and pulmonary embolism. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure. |
| Secondary | Median Time to First Cardiovascular MACE | Up to Week 208 | MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Cardiovascular MACE analysis differed from the primary MACE endpoint as it included only deaths adjudicated by the EAC as cardiovascular deaths (i.e, only EAC-confirmed cardiovascular deaths) in addition to first events of non-fatal MI or non-fatal stroke. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure. |
| Secondary | Median Time to First Cardiovascular Death | Up to Week 208 | Cardiovascular death included EAC adjudicated fatal MI, pump failure, sudden death, presumed sudden death, fatal stroke, fatal pulmonary embolism, cardiovascular procedure-related death, other cardiovascular death, and presumed cardiovascular death. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure. |
| Secondary | Median Time to First All-cause Mortality | Up to Week 208 | Only events that were positively adjudicated and confirmed by the EAC were included in the MACE analyses. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure. |
| Other | Exploratory - Proportion of Participants With Hb Values Within the Target Range During the Primary Evaluation Period (Weeks 24 to 36) | Weeks 24 to 36 | |
| Other | Exploratory - Proportion of Time With Hb Values Within the Target Range During the Primary Evaluation Period (Weeks 24 to 36) | Weeks 24 to 36 | |
| Other | Exploratory - Proportion of Time With Hb Values Within the Target Range During the Secondary Evaluation Period (Weeks 40 to 52) | Weeks 40 to 52 |
1 to 10 of 17Source ClinicalTrials.gov
See all 17 registered outcomesOutcomes17
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36) | Baseline; Weeks 24 to 36 | Randomized Population: All participants randomized. Analyses of this population were based on the randomized treatment. | Grams per deciliter (g/dL) | LEAST_SQUARES_MEAN |
| PRIMARY | Median Time to First Major Adverse Cardiovascular Event (MACE) | Up to Week 208 | Safety Population (PRO2TECT): All participants from the PRO2TECT (Non-dialysis-dependent chronic kidney disease \[NDD-CKD\]) population who received 1 or more doses of study drug. Only those participants with MACE events were analyzed for this outcome measure. | Weeks | MEDIAN |
| SECONDARY | Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52) | Baseline; Weeks 40 to 52 | Randomized Population. Analyses of this population were based on the randomized treatment. | g/dL | LEAST_SQUARES_MEAN |
| SECONDARY | Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis | Up to Week 208 | Safety Population (PRO2TECT). Only those participants with MACE plus hospitalization for heart failure or thromboembolic event excluding vascular access thrombosis were analyzed for this outcome measure. | Weeks | MEDIAN |
| SECONDARY | Median Time to First Cardiovascular MACE | Up to Week 208 | Safety Population (PRO2TECT). Only those participants with cardiovascular MACE events were analyzed for this outcome measure. | Weeks | MEDIAN |
| SECONDARY | Median Time to First Cardiovascular Death | Up to Week 208 | Safety Population (PRO2TECT). Only those participants with cardiovascular death were analyzed for this outcome measure. | Weeks | MEDIAN |
| SECONDARY | Median Time to First All-cause Mortality | Up to Week 208 | Safety Population (PRO2TECT). Only those participants with all-cause mortality were analyzed for this outcome measure. | Weeks | MEDIAN |
| OTHER_PRE_SPECIFIED | Exploratory - Proportion of Participants With Hb Values Within the Target Range During the Primary Evaluation Period (Weeks 24 to 36) | Weeks 24 to 36 | |||
| OTHER_PRE_SPECIFIED | Exploratory - Proportion of Time With Hb Values Within the Target Range During the Primary Evaluation Period (Weeks 24 to 36) | Weeks 24 to 36 | |||
| OTHER_PRE_SPECIFIED | Exploratory - Proportion of Time With Hb Values Within the Target Range During the Secondary Evaluation Period (Weeks 40 to 52) | Weeks 40 to 52 |
1 to 10 of 17Source ClinicalTrials.gov
See all 17 outcomesResults by group14
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36) | Vadadustat | 0.41 | Standard Error 0.036 | Grams per deciliter (g/dL) | |
| Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36) | Darbepoetin Alfa | 0.42 | Standard Error 0.037 | Grams per deciliter (g/dL) | |
| Median Time to First Major Adverse Cardiovascular Event (MACE) | Vadadustat | 53.21 | Inter-Quartile Range 30.64 to 81.43 | Weeks | |
| Median Time to First Major Adverse Cardiovascular Event (MACE) | Darbepoetin Alfa | 58.00 | Inter-Quartile Range 31.07 to 99.21 | Weeks | |
| Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52) | Vadadustat | 0.43 | Standard Error 0.044 | g/dL | |
| Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52) | Darbepoetin Alfa | 0.44 | Standard Error 0.044 | g/dL | |
| Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis | Vadadustat | 48.29 | Inter-Quartile Range 22.71 to 72.71 | Weeks | |
| Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis | Darbepoetin Alfa | 49.29 | Inter-Quartile Range 20.14 to 86.43 | Weeks | |
| Median Time to First Cardiovascular MACE | Vadadustat | 45.57 | Inter-Quartile Range 20.14 to 67.57 | Weeks | |
| Median Time to First Cardiovascular MACE | Darbepoetin Alfa | 50.29 | Inter-Quartile Range 18.29 to 83.29 | Weeks |
1 to 10 of 14Source ClinicalTrials.gov
See all 14 results by groupParticipant flow6
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Vadadustat | 862 | |
| Overall Study | STARTED | Darbepoetin Alfa | 863 | |
| Overall Study | COMPLETED | Vadadustat | 704 | |
| Overall Study | COMPLETED | Darbepoetin Alfa | 711 | |
| Overall Study | NOT COMPLETED | Vadadustat | 158 | |
| Overall Study | NOT COMPLETED | Darbepoetin Alfa | 152 |
Source ClinicalTrials.gov
Adverse events1,256
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Hypertension | Vascular disorders | Vadadustat | 120 | 861 | |
| other | Hypertension | Vascular disorders | Darbepoetin Alfa | 123 | 862 | |
| other | Urinary tract infection | Infections and infestations | Vadadustat | 93 | 861 | |
| other | Urinary tract infection | Infections and infestations | Darbepoetin Alfa | 113 | 862 | |
| other | Diarrhoea | Gastrointestinal disorders | Vadadustat | 117 | 861 | |
| other | Diarrhoea | Gastrointestinal disorders | Darbepoetin Alfa | 76 | 862 | |
| other | Oedema peripheral | General disorders | Vadadustat | 84 | 861 | |
| other | Oedema peripheral | General disorders | Darbepoetin Alfa | 85 | 862 | |
| other | Hyperkalaemia | Metabolism and nutrition disorders | Vadadustat | 71 | 861 | |
| other | Hyperkalaemia | Metabolism and nutrition disorders | Darbepoetin Alfa | 78 | 862 |
1 to 10 of 1,256Source ClinicalTrials.gov
See all 1,256 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Vadadustat | 139 | 861 |
| Total, all-cause mortality | Darbepoetin Alfa | 139 | 862 |
| Total, other adverse events | Vadadustat | 482 | 861 |
| Total, other adverse events | Darbepoetin Alfa | 436 | 862 |
| Total, serious adverse events | Vadadustat | 504 | 861 |
| Total, serious adverse events | Darbepoetin Alfa | 488 | 862 |
Source ClinicalTrials.gov
Papers4
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons2
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison | Source |
|---|---|
| Vadadustat vs Darbepoetin Alfa: deaths from any cause | Trial comparisons |
| Vadadustat vs Darbepoetin Alfa: serious adverse events | Trial comparisons |
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT02680574
GET https://conductscience.org/api/trials/v1/NCT02680574/events?page=2