SPICE PILOT: Spironolactone in CKD Enabled by Chlorthalidone: PILOT

Sponsor

Indiana Institute for Medical Research (Other)

Overall Status

Recruiting

CT.gov ID

NCT05222191

Collaborator

(none)

Enrollment

Location

Arms

10.3

Anticipated Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Renal Insufficiency Chronic Hypertension	Drug: Spironolactone Drug: Chlorthalidone Drug: Placebo	Phase 2

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Spironolactone in Chronic Kidney Disease Enabled by Chlorthalidone: A Pilot Randomized Control Trial

Anticipated Study Start Date :

Feb 1, 2022

Anticipated Primary Completion Date :

Dec 12, 2022

Anticipated Study Completion Date :

Dec 12, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: 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). 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).
Experimental: 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.	Drug: 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). 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).

Arm

Intervention/Treatment

Active Comparator: 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.

Drug: 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).

Drug: Placebo

Experimental: Spironolactone + Chlorthalidone

Drug: Spironolactone

Drug: Chlorthalidone

Outcome Measures

Primary Outcome Measures

Change in Systolic Automated Office Blood Pressure from baseline to 12 weeks between arms [Baseline to 12 Weeks]

Secondary Outcome Measures

Change in logarithmically transformed albumin/creatinine ratio from baseline to 12 weeks between arms [Baseline to 12 Weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 110 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age greater than 18 years.
GFR estimated by CKD-EPI formula < 45 ml/min/1.73 m2 but ≥ 15 mL/min/1.73 m2 using IDMS-calibrated creatinine.
Hypertension. Using AOBP monitoring, BP of ≥ 130/80 mmHg.
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. In patients with eGFR < 45 ml/min/1.73 m2 and serum K > 5.2 mEq/L

Exclusion Criteria:

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.
Expected to receive renal replacement therapy within the next 6 months.
Myocardial infarction, heart failure hospitalization, or stroke ≤ 12 weeks prior to randomization.
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).
Known hypersensitivity to thiazide or spironolactone.
Clinic AOBP <110 mmHg systolic at their first visit