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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called Darbepoetin, used to treat anemia, to determine its effect on blood pressure in people with chronic kidney disease and anemia. Researchers aim to find out if Darbepoetin raises diastolic blood pressure (the bottom number in a blood pressure reading) over 12 weeks. Some participants will start the treatment immediately, while others will begin after 12 weeks. The trial seeks individuals with stage 3 or 4 chronic kidney disease, controlled high blood pressure, and no treatment with similar drugs in the past three months. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that darbepoetin is likely to be safe for humans?

Research has shown that darbepoetin, also known as Aranesp®, has been tested in patients with chronic kidney disease. In these studies, high blood pressure commonly occurred as a side effect and was sometimes difficult to manage.

A large safety review revealed that about 44.4% of patients experienced unwanted effects, and 7.1% had reactions to the drug. Controlled trials identified serious risks, including a higher chance of death, major heart problems, and stroke.

This information underscores the importance of monitoring blood pressure and other health factors for those considering participation in a trial involving darbepoetin. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for high blood pressure in chronic kidney disease?

Unlike the standard treatments for high blood pressure in chronic kidney disease, which often include medications like ACE inhibitors or ARBs, Darbepoetin offers a unique approach by using a synthetic form of erythropoietin. This treatment is primarily known for stimulating red blood cell production, but researchers are exploring its potential benefits in managing blood pressure. By targeting a different mechanism, Darbepoetin might provide an alternative for those who do not respond well to traditional therapies. Researchers are excited about its potential to address both anemia and high blood pressure simultaneously, offering a novel solution for complex kidney disease management.

What evidence suggests that darbepoetin might be an effective treatment for high blood pressure in chronic kidney disease?

Research has shown that darbepoetin effectively treats anemia in people with chronic kidney disease (CKD). Studies have found that it safely maintains stable hemoglobin levels, which is crucial for managing anemia. However, some patients may experience high blood pressure. In this trial, participants will be assigned to different treatment arms: one group will receive darbepoetin immediately at randomization (Early start), while another group will begin treatment 12 weeks after randomization (Delayed start). Regarding safety, many patients have successfully used darbepoetin for an extended period. While it does not reduce the risk of other health issues like heart problems, its effectiveness in managing anemia is well-supported. ^{1 3 6 7 8}

Who Is on the Research Team?

Rajiv Agarwal, MD MBBS

Principal Investigator

Richard L. Roudebush VA Medical Center, Indianapolis, IN

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6510805/

Safety and effectiveness of long-term use of darbepoetin alfa ... This PMS study showed the safety and effectiveness of long-term use of darbepoetin in a large number of patients. Patients with Hb ≥ 11 g/dL ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa0907845

A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic ... The use of darbepoetin alfa in patients with diabetes, chronic kidney disease, and moderate anemia who were not undergoing dialysis did not reduce the risk of ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07025460

Darbepoetin Alfa Once Monthly Dosing Schedule ... This trial demonstrates that once-monthly darbepoetin alfa is non-inferior to biweekly dosing for maintaining hemoglobin in Korean patients with ND-CKD. These ...

4. aranesp.com aranesp.com/professional/oncology/efficacy_safety

Aranesp® (darbepoetin alfa) | Efficacy and Safety High blood pressure is a common side effect of Aranesp® in people with chronic kidney disease. Your blood pressure may go up or be difficult to control with ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0025619611612305

Darbepoetin Alfa Administration to Achieve and Maintain ... Darbepoetin alfa initiated every other week safely and effectively treated anemia and maintained hemoglobin for 1 year in patients with CKD who were not ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/darbepoetin-alfa-injection-route/description/drg-20068072

Darbepoetin alfa (injection route) - Side effects & dosage It has no effect on kidney disease, cancer, or any other medical problem that needs regular medical attention. Even if you are feeling much ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2011/103951orig1s5173_103951orig1s5258lbl.pdf

Aranesp (Darbepoetin alfa) Label - accessdata.fda.gov Chronic Kidney Disease: • In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when.

8. amgenesas.com amgenesas.com/aranesp/dialysis

ARANESP® (darbepoetin alfa) Dialysis HCP Information Chronic Kidney Disease: In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when ...