Spironolactone in CKD Enabled by Chlorthalidone: PILOT

NCT05222191 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: 12672
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Insufficiency; Chronic Hypertension

Keywords

Spironolactone; Chlorthalidone; Chronic Kidney Disease; Hypertension; Thiazide Diuretic; Potassium Sparring Diuretic

Outcome Measures

Primary Outcomes (1)

• Change in Systolic Automated Office Blood Pressure from baseline to 12 weeks between arms

  Baseline to 12 Weeks

Secondary Outcomes (1)

• Change in logarithmically transformed albumin/creatinine ratio from baseline to 12 weeks between arms

  Baseline to 12 Weeks

Study Arms (2)

Spironolactone + Placebo

ACTIVE COMPARATOR

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; Drug: Placebo

Spironolactone + Chlorthalidone

EXPERIMENTAL

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; Drug: Chlorthalidone

Interventions

Spironolactone 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; Spironolactone + Placebo

Chlorthalidone 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

Placebo 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 + Placebo

Eligibility Criteria

• Age: 19 Years - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Indiana Institute for Medical Research: lead

Study Sites (1)

Richard L Roudebush VA Medical Center

Indianapolis, Indiana, 46202, United States

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency; Renal Insufficiency, Chronic; Hypertension

Interventions

Spironolactone; Chlorthalidone

Condition Hierarchy (Ancestors)

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; Benzenesulfonamides; Sulfonamides; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Benzophenones; Phthalimides; Imides; Ketones; Sulfones; Sulfur Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Rajiv Agarwal, MD

  Indiana Institute for Medical Research; Roudebush VA Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rajiv Agarwal, MD

CONTACT

317-988-2241; ragarwal@iu.edu

Timothy l Ramsey, MS/MBA

CONTACT

317-988-9544; timothy.ramsey2@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 18, 2022
• First Posted: February 3, 2022
• Study Start: February 1, 2022
• Primary Completion: December 12, 2023
• Study Completion: December 12, 2023
• Last Updated: August 14, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)