Darbepoetin for High Blood Pressure in Chronic Kidney Disease

(EPIC Trial)

Overseen By Jazmyn H Dickinson, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must be taking: Antihypertensives

Disqualifiers: Recent transfusion, Heart attack, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

27 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that your high blood pressure is controlled with at least one antihypertensive medication. It seems likely you can continue your current blood pressure medication.

What data supports the effectiveness of the drug Darbepoetin for high blood pressure in chronic kidney disease?

Darbepoetin is effective in treating anemia (a condition where you don't have enough healthy red blood cells) in patients with chronic kidney disease, which can help improve overall health and quality of life. While it is not directly studied for high blood pressure, its ability to manage anemia might indirectly benefit patients with chronic kidney disease. ^{1 2 3 4 5}

Is darbepoetin safe for humans?

Darbepoetin has been studied for treating anemia in patients with chronic kidney disease, and these studies generally found it to be safe, with no significant adverse effects reported. ^{6 7 8 9 10}

How does the drug Darbepoetin differ from other treatments for high blood pressure in chronic kidney disease?

Darbepoetin is unique because it is a long-acting version of erythropoietin, allowing for less frequent dosing (once weekly or every other week) compared to other treatments that require more frequent administration. This can improve patient compliance and reduce healthcare visits. ^{3 4 10 11 12}

What is the purpose of this trial?

The investigators hypothesize that compared to untreated controls, erythropoietin (EPO) therapy in anemic patients with chronic kidney disease will raise diastolic blood pressure (BP). The magnitude of increase in diastolic BP at 12 weeks after treatment will be related to two factors. First, endothelial dysfunction and worsening of endothelial function from baseline to 4 weeks and second, the change of forearm blood flow in response to breathing oxygen and the change in this measure from baseline to 4 weeks. Study procedures include fasting blood draws, ambulatory blood pressure, urine collection, and forearm blood flow tests. The study hopes to accrue 160 subjects.

Research Team

Rajiv Agarwal, MD MBBS

Principal Investigator

Richard L. Roudebush VA Medical Center, Indianapolis, IN

Eligibility Criteria

This trial is for anemic patients with stage 3 or 4 chronic kidney disease who have a hemoglobin level between 8 and 10 g/dL, haven't used erythropoiesis-stimulating agents recently, and have controlled high blood pressure treated with medication. It's not for those who've had recent heart issues or transfusions, or other conditions affecting red blood cell production.

Inclusion Criteria

My high blood pressure is under control with medication and is below 140/90 mmHg.

I haven't taken any drugs to increase red blood cells in the last 3 months.

Your hemoglobin level is between 8 and 10 grams per deciliter.

Exclusion Criteria

I have not had a heart attack, stroke, or been hospitalized for heart failure in the last 2 months.

You have a medical condition that might affect how your body makes red blood cells.

I needed a blood transfusion in the last 2 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive EPO therapy to assess its impact on diastolic blood pressure and endothelial function

12 weeks

Frequent clinic visits for blood pressure and endothelial function assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Regular follow-up visits to monitor blood pressure changes

Extension

Participants in the delayed start group begin EPO therapy to compare outcomes with the immediate start group

12 weeks

Treatment Details

Interventions

• Darbepoetin

Trial Overview The study tests if EPO therapy raises diastolic blood pressure in anemic patients with chronic kidney disease over a period of 12 weeks. It will also examine the relationship between this potential increase and changes in endothelial function as well as forearm blood flow response to oxygen.

Participant Groups

Group I: Early start Active Control 1 Intervention

Participants given study drug immediately at randomization

Group II: Delayed start Active Control 1 Intervention

Participants given study drugs 12 weeks after randomization

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

Effect of darbepoetin alfa administered once monthly on maintaining hemoglobin levels in older patients with chronic kidney disease. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Greater potency of darbepoetin-α than erythropoietin in suppression of serum hepcidin-25 and utilization of iron for erythropoiesis in hemodialysis patients. [2022]

3. Spain pubmed.ncbi.nlm.nih.gov

Darbepoetin alfa: a novel erythropoiesis-stimulating protein. [2019]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Darbepoetin alfa: its use in anemia associated with chronic kidney disease. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Dosing patterns, hematologic outcomes, and costs of erythropoietic agents in predialysis chronic kidney disease patients with anemia. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Anemia treatment with Q2W darbepoetin alfa in patients with chronic kidney disease naïve to erythropoiesis-stimulating agents. [2021]

7. Japan pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of long-term use of darbepoetin alfa in non-dialysis patients with chronic kidney disease: a post-marketing surveillance study in Japan. [2020]

8. Germany pubmed.ncbi.nlm.nih.gov

De novo weekly and biweekly darbepoetin alfa dosing in pediatric patients with chronic kidney disease. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Darbepoetin alfa administration to achieve and maintain target hemoglobin levels for 1 year in patients with chronic kidney disease. [2015]

10. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Initiation of darbepoetin for management of anemia in non-dialysis-dependent patients with chronic kidney disease. [2019]

11. Korea (South) pubmed.ncbi.nlm.nih.gov

Pretreatment with darbepoetin attenuates renal injury in a rat model of cisplatin-induced nephrotoxicity. [2022]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Darbepoetin alfa. [2018]