Diuretics and Volume Overload in Early CKD

NCT05171686 | Completed Phase 4 DMC FDA Drug

• 2 other identifiers: NEPH-001-21S1IK2CX002368-01A1
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

Almost 15% of Americans have chronic kidney disease (CKD), with an even higher rate in Veterans due to common risk factors such as high blood pressure and diabetes. People with CKD have a high risk of cardiovascular (CV) diseases, such as heart attacks, heart failure, and strokes. Extra fluid in the body, called volume overload, may lead to CV disease in people with CKD. It is unknown if volume overload develops in the earliest stages of CKD, when treating it with common, inexpensive medicines called diuretics may improve long-term CV outcomes. This study will lay important groundwork to answer this question in Veterans with early CKD by comparing two ways to measure volume overload and studying the change in common symptoms like fatigue and short-term CV function after treatment with diuretic medicines.

Conditions

Chronic Kidney Disease; Hypertension

Keywords

diuretic; chronic kidney disease; hypertension; extracellular volume; natriuretic peptides

Outcome Measures

Primary Outcomes (1)

• Change in NT-pro-BNP

  Change in NT-pro-BNP from baseline to 4 weeks after intervention

  4 weeks

Secondary Outcomes (11)

• Change in BNP

  4 weeks

• Change in FACIT-F score

  4 weeks

• Change in QIDS-SR16

  4 weeks

• Change in KDQOL

  4 weeks

• Change in total peripheral resistance index

  4 weeks

Study Arms (1)

Diuretic augmentation

EXPERIMENTAL

The participant's blood pressure medication regimen will be altered to initiate a thiazide-type or loop diuretic in those not already prescribed a diuretic, or to increase the dose if one is already prescribed.

Drug: Diuretic augmentation (hydrochlorothiazide, chlorthalidone, furosemide, torsemide, or bumetanide)

Interventions

Diuretic augmentation (hydrochlorothiazide, chlorthalidone, furosemide, torsemide, or bumetanide) DRUG

The participant's blood pressure medication regimen will then be altered to initiate a thiazide-type (hydrochlorothiazide or chlorthalidone) or loop diuretic (furosemide, bumetanide, or torsemide) in those not already prescribed a diuretic, or to increase the dose if one is already prescribed

Diuretic augmentation

Eligibility Criteria

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

You may qualify if:

• Male or female Veterans age 18 years or older. There will be no upper age limit.
• The presence of CKD stages 1, 2, or 3, as defined below by Kidney Disease Improving Global Outcomes guidelines, for a period of at least 3 months.
• Stage 1: eGFR 90 mL/min/1.73 m2 and spot urine albumin-to-creatinine ratio 30 mg/g.
• Stage 2: eGFR 60-89 mL/min/1.73 m2 and spot urine albumin-to-creatinine ratio 30 mg/g.
• Stage 3: eGFR 30-59 mL/min/1.73 m2.
• Measured blood pressure either \>140 mmHg systolic or \>90 mmHg diastolic at the two most recent clinic visits.
• Able to understand and sign informed consent after the nature of the study has been fully explained.

You may not qualify if:

• Unable to understand or provide informed consent.
• Unwilling or unable to participate in the protocol or comply with any of its components.
• CKD stages 4-5, defined as eGFR \<30 mL/min/1.73 m2.
• Receiving chronic hemodialysis or peritoneal dialysis.
• Recipient of a kidney transplant.
• Serum potassium \<3.5 mEq/L at baseline.
• Known left ventricular ejection fraction \<40% on visual estimate based on chart review of available echocardiogram data.
• Known hepatic cirrhosis.
• Major limb amputation.
• Known pregnancy.
• Presence of a pacemaker or defibrillator.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030-4211, United States

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Hypertension

Interventions

Hydrochlorothiazide; Chlorthalidone; Furosemide; Torsemide; Bumetanide

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; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Benzenesulfonamides; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Benzophenones; Phthalimides; Imides; Ketones; Isoindoles; Sulfanilamides; Aniline Compounds; Amines; Pyridines; Heterocyclic Compounds, 1-Ring; meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids

Study Officials

• Lucile P Gregg, MD MS

  Michael E. DeBakey VA Medical Center, Houston, TX

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Open label single arm clinical trial

Study Record Dates

• First Submitted: December 1, 2021
• First Posted: December 29, 2021
• Study Start: February 1, 2023
• Primary Completion: October 2, 2025
• Study Completion: October 2, 2025
• Last Updated: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)