Association of Diuretics With Change in Extracellular Volume, Natriuretic Peptides, Symptoms, and Cardiovascular Outcomes in CKD

NCT04192110 | Withdrawn Phase 4 DMC FDA Drug

• 2 other identifiers: NEPH-025-19S1IK2CX002030-01
• Study Type: interventional
• Target: N/A
• 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

Keywords

Chronic kidney disease; Diuretics; Volume overload; Natriuretic peptides; Bioimpedance spectroscopy; Cardiovascular disease

Outcome Measures

Primary Outcomes (2)

• NT-pro-BNP

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

  4 weeks

• Total peripheral resistance index

  The change from baseline to 4 weeks in total peripheral resistance index will be measured using Non-Invasive Cardiac Output Monitoring (Cheetah)

  4 weeks

Secondary Outcomes (10)

• BNP

  4 weeks

• Fatigue

  4 weeks

• Depression

  4 weeks

• Quality of Life - Kidney Disease Quality of Life (KDQOL)

  4 weeks

• Hospitalizations

  6 months

Other Outcomes (1)

• Evolume

  4 weeks

Study Arms (1)

Diuretic initiation or augmentation

EXPERIMENTAL

Participants will either initiate or increase the dose of a loop or thiazide-type diuretic

Drug: Diuretic initiation or augmentation

Interventions

Diuretic initiation or augmentation 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 initiation or augmentation

Eligibility Criteria

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

You may qualify if:

• The presence of CKD stages 1, 2, or 3, as defined below by National Kidney Foundation 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.
• Rationale: The investigators' unpublished preliminary data show that blood pressure correlates with both BNP and NT-pro-BNP more strongly in those with CKD than those without CKD. Thus, selecting hypertensive individuals is more likely to identify those with elevated natriuretic peptides in the CKD group.
• Furthermore, starting or increasing a diuretic medication is part of standard of care to treat blood pressures \>140/90 mmHg, so the study intervention will be consistent with appropriate care for the Veteran and avoid hypotension.
• 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 mg/dL 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.
• Presence of metal prostheses.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX

Dallas, Texas, 75216, United States

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Edema; Cardiovascular Diseases

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; Signs and Symptoms

Study Officials

• Lucile P Gregg, MD

  VA North Texas Health Care System Dallas VA Medical Center, Dallas, 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: Single group open label initiation or dose increase of loop or thiazide-type diuretics

Study Record Dates

• First Submitted: December 6, 2019
• First Posted: December 10, 2019
• Study Start: August 11, 2020
• Primary Completion: August 11, 2020
• Study Completion: August 11, 2020
• Last Updated: December 9, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)