Patiromer to Enable Spironolactone Use in the Treatment of Patients with Resistant Hypertension and Chronic Kidney Disease: Rationale and Design of the AMBER Study

Abstract

Background: While chronic kidney disease (CKD) is common in resistant hypertension (RHTN), prior studies -evaluating mineralocorticoid receptor antagonists excluded patients with reduced kidney function due to risk of hyperkalemia. AMBER (ClinicalTrials.gov identifier NCT03071263) will evaluate if the potassium-binding polymer patiromer used concomitantly with spironolactone in patients with RHTN and CKD prevents hyperkalemia and allows more persistent spironolactone use for hypertension management.

Methods: Randomized, double-blind, placebo-controlled parallel group 12-week study of patiromer and spironolactone versus placebo and spironolactone in patients with uncontrolled RHTN and CKD. RHTN is defined as unattended systolic automated office blood pressure (AOBP) of -135-160 mm Hg during screening despite taking ≥3 antihypertensives, including a diuretic, and an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker -(unless not tolerated or contraindicated). The CKD inclusion criterion is an estimated glomerular filtration rate (eGFR) of 25 to ≤45 mL/min/1.73 m2. Screening serum potassium must be 4.3-5.1 mEq/L. The primary efficacy endpoint is the between-group difference (spironolactone plus patiromer versus spironolactone plus placebo) in the proportion of patients remaining on spironolactone at Week 12.

Results: Baseline characteristics have been analyzed as of March 2018 for 146 (of a targeted 290) patients. Mean (SD) baseline age is 69.3 (10.9) years; 52.1% are male, 99.3% White, and 47.3% have diabetes. Mean (SD) baseline serum potassium is 4.68 (0.25) mEq/L, systolic AOBP is 144.3 (6.8) mm Hg, eGFR is 35.7 (7.7) mL/min/1.73 m2.

Conclusion: AMBER will define the ability of patiromer to facilitate the use of spironolactone, an effective antihypertensive therapy for patients with RHTN and CKD.

Keywords: Chronic kidney disease; Hyperkalemia; Patiromer; Resistant hypertension; Spironolactone.

Fig. 1

AMBER study design. AOBP, automated office blood pressure; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HBP, home blood pressure. * To ensure eligibility criteria, stable medication, and competent use of HBP monitor.

Fig. 2

Spironolactone dosing algorithm. AOBP, automated office blood pressure; K⁺, potassium; PI, principal investigator. * Investigator determined. ^†If spironolactone is discontinued, patiromer/placebo must be discontinued at the same time.

Fig. 3

Patiromer dosing algorithm. K⁺, potassium. * Each packet contains patiromer (4.2 g) or microcrystalline cellulose placebo. ^†All dose increases should be made no less than 1 week apart. ^‡ After discontinuation, hyperkalemia may be treated at any time using standard of care per Investigator judgment.