Spironolactone in CKD Enabled by Chlorthalidone: PILOT

NCT ID: NCT05222191

Last Updated: 2023-08-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-01
• Study Completion Date: 2023-12-12

Brief Summary

Highly prevalent among patients with chronic kidney disease (CKD) and poorly controlled blood pressure (BP), is a modifiable risk factor to abrogate both kidney failure progression and cardiovascular (CV) disease. Spironolactone (SPL), a mineralocorticoid receptor antagonist, is widely used to treat resistant hypertension, however one of the most common side effects is an increase of serum potassium (K). This side effect occurs frequently in those who suffer from CKD. Alternatively, chlorthalidone (CTD) is a thiazide-like diuretic used for treating hypertension and decreases serum K. In this pilot study, our goal is to assess whether the combination of SPL and CTD can improve BP control, while also reducing the risk of hyperkalemia over a period of 12 weeks. We hypothesize that among patients with CKD and poorly controlled hypertension, compared to SPL and placebo, treatment over 12 weeks with CTD will counter the hyperkalemia effect of SPL, and therefore the combination of SPL with CTD will result in a lower BP. This pilot study will be performed at Richard L. Roudebush VA in Indianapolis, Indiana.

Detailed Description

This is a placebo-controlled, double-blind, randomized controlled trial of spironolactone (SPL) and chlorthalidone (CTD) in patients with CKD and poorly controlled hypertension

Conditions

Renal Insufficiency; Chronic Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Spironolactone + Placebo

Subjects with stage 3B/4 chronic kidney disease and poorly controlled hypertension will be randomized into two groups: one receiving spironolactone and placebo and one receiving spironolactone and chlorthalidone. At randomization, subjects will begin at 25 mg spironolactone and 6.25 mg placebo/chlorthalidone daily.

Group Type: ACTIVE_COMPARATOR

Spironolactone

Intervention Type: DRUG

Study drugs will be increased if goal blood pressure is not achieved and/or serum potassium is not in safe clinical range (dosage of chlorthalidone/placebo not to exceed 25 mg daily; dosage of spironolactone not to exceed 50 mg daily).

Placebo

Intervention Type: DRUG

Study drugs will be increased if goal blood pressure is not achieved and/or serum potassium is not in safe clinical range (dosage of chlorthalidone/placebo not to exceed 25 mg daily; dosage of spironolactone not to exceed 50 mg daily).

Spironolactone + Chlorthalidone

Subjects with stage 3B/4 chronic kidney disease and poorly controlled hypertension will be randomized into two groups: one receiving spironolactone and placebo and one receiving spironolactone and chlorthalidone. At randomization, subjects will begin at 25 mg spironolactone and 6.25 mg placebo/chlorthalidone daily.

Group Type: EXPERIMENTAL

Spironolactone

Intervention Type: DRUG

Study drugs will be increased if goal blood pressure is not achieved and/or serum potassium is not in safe clinical range (dosage of chlorthalidone/placebo not to exceed 25 mg daily; dosage of spironolactone not to exceed 50 mg daily).

Chlorthalidone

Intervention Type: DRUG

Study drugs will be increased if goal blood pressure is not achieved and/or serum potassium is not in safe clinical range (dosage of chlorthalidone/placebo not to exceed 25 mg daily; dosage of spironolactone not to exceed 50 mg daily).

Interventions

Spironolactone

Study drugs will be increased if goal blood pressure is not achieved and/or serum potassium is not in safe clinical range (dosage of chlorthalidone/placebo not to exceed 25 mg daily; dosage of spironolactone not to exceed 50 mg daily).

Intervention Type: DRUG

Chlorthalidone

Study drugs will be increased if goal blood pressure is not achieved and/or serum potassium is not in safe clinical range (dosage of chlorthalidone/placebo not to exceed 25 mg daily; dosage of spironolactone not to exceed 50 mg daily).

Intervention Type: DRUG

Placebo

Study drugs will be increased if goal blood pressure is not achieved and/or serum potassium is not in safe clinical range (dosage of chlorthalidone/placebo not to exceed 25 mg daily; dosage of spironolactone not to exceed 50 mg daily).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age greater than 18 years.

2. GFR estimated by CKD-EPI formula < 45 ml/min/1.73 m2 but ≥ 15 mL/min/1.73 m2 using IDMS-calibrated creatinine.

3. Hypertension. Using AOBP monitoring, BP of ≥ 130/80 mmHg.

4. 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.

5. Serum K 3.5 to 5.2 mEq/L at the time of randomization. In patients with eGFR < 45 ml/min/1.73 m2 and serum K > 5.2 mEq/L

Exclusion Criteria

1. Use of spironolactone, eplerenone, amiloride, triamterene, thiazides, or thiazide-like drugs or the use of K supplements or K binders in the previous 12 weeks.

2. Expected to receive renal replacement therapy within the next 6 months.

3. Myocardial infarction, heart failure hospitalization, or stroke ≤ 12 weeks prior to randomization.

4. Pregnant or breastfeeding women or women who are planning to become pregnant or those not using a reliable form of contraception (oral contraceptives. condoms and diaphragms will be considered reliable).

5. Known hypersensitivity to thiazide or spironolactone.

6. Clinic AOBP <110 mmHg systolic at their first visit

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 110 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Indiana Institute for Medical Research

OTHER

Sponsor Role: lead

Responsible Party

Rajiv Agarwal

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rajiv Agarwal, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana Institute for Medical Research; Roudebush VA Medical Center

Locations

Richard L Roudebush VA Medical Center

Indianapolis, Indiana, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Rajiv Agarwal, MD

Role: CONTACT

ragarwal@iu.edu

317-988-2241

Timothy l Ramsey, MS/MBA

Role: CONTACT

timothy.ramsey2@va.gov

317-988-9544

Facility Contacts

Timothy l ramsey, ms

Role: primary

timothy.ramsey2@va.gov

317-988-9544

Other Identifiers

12672

Identifier Type: -

Identifier Source: org_study_id