LOw DosE Spironolactone, chlorThAlidone oR Combination in CKD Trial (LODESTAR)

June 8, 2026 updated by: VA Office of Research and Development

LOw DosE Spironolactone, chlorThAlidone oR Combination in CKD (LODESTAR) Trial

The purpose of this research is to gather information on the safety and effectiveness of spironolactone and chlorthalidone for treatment of high blood pressure in patients with moderate to advanced CKD. Both drugs have been approved by the Food and Drug Administration (FDA) for the treatment of high blood pressure since 1960.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Highly prevalent among patients with chronic kidney disease (CKD) , poor blood pressure (BP) control is a modifiable risk factor for both kidney failure progression and cardiovascular (CV) disease. Although the mineralocorticoid receptor antagonist (MRA) spironolactone (SPL) is recommended to treat resistant hypertension in patients with CKD, 34% discontinue SPL within 12 weeks, mostly due to hyperkalemia. The potassium (K) binding agent patiromer reduced the discontinuation rate to 14%, but the added expense and potential drug interactions are of concern. SPL, a steroidal MRA, reduces albuminuria and rates of decline in eGFR. In type 2 diabetes and CKD, the non-steroidal MRA finerenone reduces kidney failure and CV outcomes but is not indicated for the treatment of hypertension. Due to concern of hyperkalemia, SPL is barely prescribed in these patients. In 2021, the investigators reported that chlorthalidone (CTD) in people with advanced CKD was effective in lowering BP and albuminuria by 50%. However, reversible changes in kidney function and hypokalemia were common. The investigators believe that a very low dose combination strategy of CTD + SPL will be effective in lowering BP, maintaining K, and providing target organ protection. However, the optimal dose to maintain K and lower BP remains unclear. To test this hypothesis, the investigators propose a pilot proof-of-concept study (phase 2A) followed by a larger phase 2B study. Proof of Concept, phase 2A: To test the hypothesis that low or very low dose CTD combined with SPL will improve BP, the investigators will perform a pilot, single-center, placebo-controlled, double-blind, randomized trial among patients with CKD and poorly controlled hypertension. After a two-week, patient-blind, placebo run-in, the investigators will randomize 50 hypertensive people to one of 4 groups in equal numbers: placebo; CTD very low dose; SPL very low dose QD; or a combination of CTD very low dose + SPL very low dose for 6 weeks. At 6 weeks, doses will be doubled for a further 6 weeks. The primary endpoint will be assessed by change from baseline to 6 weeks and 12 weeks in systolic AOBP and serum K for the combination group compared to placebo. If CTD + SPL is more effective than placebo, the investigators will perform the phase 2B trial. In this trial, the investigators will test the hypothesis that among patients with moderate to advanced CKD and poorly controlled hypertension, compared to add-on SPL or add-on CTD, treatment over 12 weeks with add-on combination of spironolactone (SPL) and chlorthalidone (CTD) will more effectively lower unattended systolic automated office blood pressure (uAOBP). Furthermore, combination therapy will reduce albuminuria more than either drug alone providing evidence for target organ protection. CTD will produce these effects by further reducing extracellular fluid volume in combination with SPL.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
160

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202-2884
        • Richard L. Roudebush VA Medical Center, Indianapolis, IN
        • Principal Investigator:
          • Rajiv Agarwal, MD MBBS
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Study is limited to US Veterans
  • GFR estimated by race-independent CKD-EPI formula < 45 ml/min/1.73m2 but 15 mL/min/1.73m2

  • Hypertension

    • The investigators will use clinic AOBP of at least 135/85 to define hypertension

  • Treatment with antihypertensive drugs

    • This would require the use of at least one antihypertensive drug
    • One of the drugs should be either an ACE inhibitor or ARB or a beta-blocker at the time of randomization
  • Serum K 3.5 to 5.2 mEq/L at the time of randomization

Exclusion Criteria:

  • Clinic AOBP of >=160/100 mmHg

  • Use of:

    • SPL
    • eplerenone
    • amiloride
    • triamterene
    • finerenone
    • thiazide
    • thiazide-like drugs (CTD, HCTZ, metolazone, indapamide) or the use of K binders or fludrocortisone in the previous 4 weeks
    • K supplementation would be allowed
  • Myocardial infarction, heart failure hospitalization, or stroke 8 weeks prior to randomization
  • If the patient is only on an alpha blocker, as the sole antihypertensive drug, they will be excluded
  • Pregnant or breastfeeding women or women who are planning to become pregnant or those not using a reliable form of contraception
  • Known hypersensitivity or a prior documented adverse reaction to CTD or SPL

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: placebo
phase 2A
Drug: phase 2A Chlorthalidone
very low dose (VLD) x 6 weeks then low dose (LD) x 6 weeks
Drug: phase 2A Spironolactone
very low dose (VLD) x 6 weeks then low dose (LD) x 6 weeks
Drug: phase 2A Chlorthalidone + Spironolactone
very low dose (VLD) x 6 weeks then low dose (LD) x 6 weeks
Experimental: Chlorthalidone
phase 2A Chlorthalidone(CTD) very low dose (VLD) x 6 weeks
Drug: phase 2A Chlorthalidone
very low dose (VLD) x 6 weeks then low dose (LD) x 6 weeks
Experimental: Spironolactone
phase 2A Spironolactone(SPL) very low dose (VLD) x 6 weeks
Drug: phase 2A Spironolactone
very low dose (VLD) x 6 weeks then low dose (LD) x 6 weeks
Experimental: CTD + SPL
phase 2A Chlorthalidone(CTD) VLD + Spironolactone(SPL) VLD x 6 weeks
Drug: phase 2A Chlorthalidone + Spironolactone
very low dose (VLD) x 6 weeks then low dose (LD) x 6 weeks
Active Comparator: 2B CTD
phase 2B Chlorthalidone(CTD) low dose (LD) x 12 weeks
Drug: phase 2B Chlorthalidone LD + Spironolactone LD
compare combination LD with SPL LD at 12 weeks
Active Comparator: 2B SPL
phase 2B Spironolactone(SPL) low dose (LD) x 12 weeks
Drug: phase 2B Chlorthalidone LD + Spironolactone LD
compare combination LD with SPL LD at 12 weeks
Experimental: 2B VLD CTD + VLD SPL
phase 2B Chlorthalidone(CTD) VLD + Spironolactone(SPL) VLD x 12 weeks
Drug: phase 2B Chlorthalidone LD + Spironolactone LD
compare combination LD with SPL LD at 12 weeks
Experimental: 2B LD CTD + LD SPL
phase 2B Chlorthalidone(CTD) LD + Spironolactone(SPL) LD x 12 weeks
Drug: phase 2B Chlorthalidone LD + Spironolactone LD
compare combination LD with SPL LD at 12 weeks

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Unattended systolic automated office blood pressure in phase 2A
Time Frame: 12 weeks
phase 2A: the primary endpoint will be assessed by change from baseline to 6 weeks and 12 weeks in systolic AOBP for the combination group compared to placebo.
12 weeks
Serum K phase 2A
Time Frame: 12 weeks
phase 2A: the primary endpoint will be assessed by change from baseline to 12 weeks in serum K for the combination group compared to placebo.
12 weeks
Unattended systolic automated office blood pressure in phase 2B
Time Frame: 12 weeks
phase 2B: the primary endpoint will be assessed by change from baseline to 12 weeks in systolic AOBP for the combination LD group compared to SPL.
12 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mediation of BP lowering by volume markers
Time Frame: 12 weeks
The investigators will evaluate changes from baseline in the following markers: B-type natriuretic peptide (BNP), seated plasma renin activity and plasma aldosterone, and 24h urinary aldosterone. The investigators will use a mediation model to ascertain the mechanism of BP lowering whether it is via reduction of volume or blockade of the renin-angiotensin system. Each of the 4 mediation variables will be analyzed individually and then in aggregate as prespecified in the statistical analysis plan.
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
VA Office of Research and Development

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Michael E. DeBakey VA Medical Center
VA Salt Lake City Health Care System

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Rajiv Agarwal, MD MBBS, Richard L. Roudebush VA Medical Center, Indianapolis, IN

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 31, 2032

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2032

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 8, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 8, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 12, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 12, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 8, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NEPH-011-25F

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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