Combining spironolactone and chlorthalidone for better blood pressure control in chronic kidney disease

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

This study is testing if combining two blood pressure medications, spironolactone and chlorthalidone, can help people with chronic kidney disease better control their blood pressure without causing too much potassium in their blood.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 19 Years to 110 Years
• Sex: All
• Sponsor: Indiana Institute for Medical Research (Academic / other)
• Locations: 1 site (Indianapolis, Indiana)
• Trial ID: NCT05222191 on ClinicalTrials.gov

What this trial studies

This pilot study investigates the effects of combining spironolactone, a medication for resistant hypertension, with chlorthalidone, a thiazide-like diuretic, in patients with chronic kidney disease (CKD) and poorly controlled hypertension. The study is designed as a placebo-controlled, double-blind, randomized controlled trial, aiming to determine if this combination can improve blood pressure control while minimizing the risk of hyperkalemia, a common side effect of spironolactone. Over a 12-week period, participants will receive either the combination treatment or a placebo, with careful monitoring of their blood pressure and serum potassium levels.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with CKD (GFR < 45 ml/min/1.73 m2) and poorly controlled hypertension (BP ≥ 130/80 mmHg).

Not a fit: Patients who have recently used certain diuretics or potassium supplements, or those expected to require renal replacement therapy soon, may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a safer and more effective treatment option for patients with CKD and hypertension.

How similar studies have performed: While the combination of these medications is a novel approach, previous studies have shown success with spironolactone in hypertension management, indicating potential for this strategy.

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

Where this trial is running

Indianapolis, Indiana

• Richard L Roudebush VA Medical Center — Indianapolis, Indiana, United States (Recruiting)

Study contacts

• Principal investigator: Rajiv Agarwal, MD — Indiana Institute for Medical Research; Roudebush VA Medical Center
• Study coordinator: Rajiv Agarwal, MD

Conditions Renal Insufficiency; Chronic Hypertension; Spironolactone; Chlorthalidone; Chronic Kidney Disease; Hypertension; Thiazide Diuretic; Potassium Sparring Diuretic