Mechanisms of EPO-induced Hypertension

NCT03810911 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: NEPH-005-18S052387
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Kidney Disease; Blood Pressure; Anemia

Keywords

Flow mediated dilatation

Outcome Measures

Primary Outcomes (2)

• Change in Diastolic Blood Pressure in EPO Treated Patients Compared to Delayed Start Controls

  In the delayed start group (the control group), the investigators will measure the change in diastolic blood pressure from 0 weeks to 12 weeks compared to the change in diastolic BP from 0 to 12 weeks in the immediate start group.

  Baseline to 12 weeks

• Within Group Change in Diastolic Blood Pressure in the Delayed Start Group

  Within group change in diastolic blood pressure from 12 weeks to 24 weeks compared to change in diastolic blood pressure from baseline to 12 weeks in the delayed start group

  12 to 24 weeks compared to baseline to 12 weeks

Secondary Outcomes (5)

• Change in Systolic Blood Pressure in EPO Treated Patients Compared to Delayed Start Controls

  Baseline to 12 weeks

• Number of Participants With Worsened Hypertension Status in Immediate Start Group Compared to Delayed Start Controls

  Baseline to 12 weeks

• Number of Participants With Worsened Hypertension Status in Delayed Start Group Participants When They Were Not on EPO Compared to When They Were on EPO

  baseline to 12 weeks vs 12 weeks to 24 weeks

• Change in Endothelial Function in Those Treated With EPO Compared to the Waitlisted Group

  Baseline to 4 weeks

• Change in Urine Albumin to Urine Creatinine Ratio in the Delayed Start Group

  Baseline to 16 weeks, baseline to 20 weeks, and baseline to 24 weeks

Study Arms (2)

Early start

ACTIVE COMPARATOR

Participants given study drug immediately at randomization

Drug: Darbepoetin

Delayed start

NO INTERVENTION

Participants given study drugs 12 weeks after randomization

Interventions

Darbepoetin DRUG

Used to treat anemia. In the group labeled no intervention, the intervention is simply delayed 12 weeks after randomization as noted in the description.

Also known as: EPO

Early start

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stage 3 or 4 chronic kidney disease
• Controlled hypertension with 24 hour ambulatory blood pressure monitoring less than 140/90 mmHg at baseline and treatment with at least 1 antihypertensive medication
• Hemoglobin between 8 and 10 g/dL
• No treatment with erythropoiesis-stimulating agents (ESA) within 3 previous months

You may not qualify if:

• Need for packed red blood cells (RBC) transfusion in the previous 2 months
• Myocardial infarction, stroke or hospitalization for heart failure in the past 2 months
• In the assessment of the investigator, have hematologic, inflammatory, infectious, or other conditions that might interfere with the erythropoietic response

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Richard L. Roudebush VA Medical Center, Indianapolis, IN

Indianapolis, Indiana, 46202-2884, United States

Location

Related Publications (1)

• Georgianos PI, Agarwal R. Resistant Hypertension in Dialysis: Epidemiology, Diagnosis, and Management. J Am Soc Nephrol. 2024 Apr 1;35(4):505-514. doi: 10.1681/ASN.0000000000000315. Epub 2024 Jan 16.

  PMID: 38227447 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Anemia

Interventions

Darbepoetin alfa

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins

Limitations and Caveats

The trial was limited by the absence of enough patients to observe a meaningful change in 24-hour ambulatory BP or endothelial function.

Results Point of Contact

• Title: Dr. Rajiv Agarwal MD MS
• Organization: Richard L. Roudebush Veterans Affairs Medical Center

ragarwal@iu.edu

(317) 988-2241

Study Officials

• Rajiv Agarwal, MD MBBS

  Richard L. Roudebush VA Medical Center, Indianapolis, IN

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The groups are randomized not the study drug. The groups will be known by both the participant and the investigator.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: All subjects will receive darbepoetin during the study. One group, the immediate start group, will receive the drug the day of randomization. The other group, the delayed start group, will receive the drug 12 weeks later.

Study Record Dates

• First Submitted: January 7, 2019
• First Posted: January 22, 2019
• Study Start: January 4, 2021
• Primary Completion: December 31, 2024
• Study Completion: July 31, 2025
• Last Updated: December 15, 2025
• Results First Posted: December 15, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)