LOw DosE Spironolactone, chlorThAlidone oR Combination in CKD Trial

NCT07645300 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: NEPH-011-25F
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypertension Treated With Antihypertensive Drugs; Chronic Kidney Disease, 3B and 4

Keywords

hypertension; chronic kidney disease

Outcome Measures

Primary Outcomes (3)

• Unattended systolic automated office blood pressure in phase 2A

  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

  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

  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 Outcomes (1)

• Mediation of BP lowering by volume markers

  12 weeks

Study Arms (8)

placebo

PLACEBO COMPARATOR

phase 2A

Drug: phase 2A Chlorthalidone; Drug: phase 2A Spironolactone; Drug: phase 2A Chlorthalidone + Spironolactone

Chlorthalidone

EXPERIMENTAL

phase 2A Chlorthalidone(CTD) very low dose (VLD) x 6 weeks

Drug: phase 2A Chlorthalidone

Spironolactone

EXPERIMENTAL

phase 2A Spironolactone(SPL) very low dose (VLD) x 6 weeks

Drug: phase 2A Spironolactone

CTD + SPL

EXPERIMENTAL

phase 2A Chlorthalidone(CTD) VLD + Spironolactone(SPL) VLD x 6 weeks

Drug: phase 2A Chlorthalidone + Spironolactone

2B CTD

ACTIVE COMPARATOR

phase 2B Chlorthalidone(CTD) low dose (LD) x 12 weeks

Drug: phase 2B Chlorthalidone LD + Spironolactone LD

2B SPL

ACTIVE COMPARATOR

phase 2B Spironolactone(SPL) low dose (LD) x 12 weeks

Drug: phase 2B Chlorthalidone LD + Spironolactone LD

2B VLD CTD + VLD SPL

EXPERIMENTAL

phase 2B Chlorthalidone(CTD) VLD + Spironolactone(SPL) VLD x 12 weeks

Drug: phase 2B Chlorthalidone LD + Spironolactone LD

2B LD CTD + LD SPL

EXPERIMENTAL

phase 2B Chlorthalidone(CTD) LD + Spironolactone(SPL) LD x 12 weeks

Drug: phase 2B Chlorthalidone LD + Spironolactone LD

Interventions

phase 2A Chlorthalidone DRUG

very low dose (VLD) x 6 weeks then low dose (LD) x 6 weeks

Chlorthalidone; placebo

phase 2A Spironolactone DRUG

very low dose (VLD) x 6 weeks then low dose (LD) x 6 weeks

Spironolactone; placebo

phase 2B Chlorthalidone LD + Spironolactone LD DRUG

compare combination LD with SPL LD at 12 weeks

2B CTD; 2B LD CTD + LD SPL; 2B SPL; 2B VLD CTD + VLD SPL

phase 2A Chlorthalidone + Spironolactone DRUG

very low dose (VLD) x 6 weeks then low dose (LD) x 6 weeks

CTD + SPL; placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Michael E. DeBakey VA Medical Center: collaborator
• VA Salt Lake City Health Care System: collaborator

Study Sites (1)

Richard L. Roudebush VA Medical Center, Indianapolis, IN

Indianapolis, Indiana, 46202-2884, United States

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Hypertension

Interventions

Spironolactone

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)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Rajiv Agarwal, MD MBBS

  Richard L. Roudebush VA Medical Center, Indianapolis, IN

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rajiv Agarwal, MD MBBS

CONTACT

(317) 988-2241; rajiv.agarwal@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double dummy, double blind, placebo controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: phase 2 A: Arm 1: placebo + placebo; Arm 2: placebo + spironolactone (SPL) very low dose (VLD); Arm 3: placebo + chlorthalidone (CTD) VLD; Arm 4: spironolactone VLD + chlorthalidone VLD. At 6 weeks, dose is doubled for further 6 weeks. phase 2 B: Arm 1: placebo + SPL LD; Arm 2: placebo + CTD LD; Arm 3: CTD VLD + SPL VLD; Arm 4: CTD LD + SPL LD all give 12 weeks

Study Record Dates

• First Submitted: June 8, 2026
• First Posted: June 12, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): March 31, 2032
• Study Completion (Estimated): June 30, 2032
• Last Updated: June 12, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)