Spironolactone in CKD Enabled by Chlorthalidone: PILOT

Renal Insufficiency Clinical Trial

— SPICE PILOT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05222191
• Other study ID #: 12672
• Status: Recruiting
• Phase: Phase 2
• Start date: February 1, 2022
• Est. completion date: December 12, 2023

Study information

• Verified date: August 2023
• Source: Indiana Institute for Medical Research
• Contact: Rajiv Agarwal, MD
• Phone: 317-988-2241
• Email: ragarwal[@]iu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: December 12, 2023
• Est. primary completion date: December 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 110 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hypertension
• Hypertension
• Renal Insufficiency

Intervention

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).
• 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).
• 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).

Locations

Country	Name	City	State
United States	Richard L Roudebush VA Medical Center	Indianapolis	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Indiana Institute for Medical Research

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Systolic Automated Office Blood Pressure from baseline to 12 weeks between arms		Baseline to 12 Weeks
Secondary	Change in logarithmically transformed albumin/creatinine ratio from baseline to 12 weeks between arms		Baseline to 12 Weeks