Official Title: “Randomized Trial of Spironolactone Versus Amiloride as an Add on Agent in Resistant Hypertension”

Joint National Committee 7 (JNC-7) defines resistant hypertension as a persistent elevation of blood pressure (BP) above goal - ≥ 140/90 mm Hg for the general hypertensive population or ≥ 130/80 mm Hg for persons with diabetes mellitus or chronic kidney disease - for at least three months despite treatment with three or more optimally dosed antihypertensive agents, including a diuretic. The exact prevalence of resistant hypertension is uncertain but may include 5-20% of hypertensive persons in primary care settings and 15-35% of the older, higher cardiovascular risk hypertensive patients incorporated into recent clinical trials of antihypertensive therapy. Observational studies demonstrate that patients with resistant hypertension experience a higher rate of cardiovascular and renal target organ damage such as left ventricular hypertrophy, microalbuminuria, and renal insufficiency and more cardiovascular disease (CVD) events than patients whose hypertension is well-controlled.

Additionally, resistant hypertension patients may be subjected to the considerable expense of multiple office visits, diagnostic testing for secondary causes of hypertension, and referral to hypertension specialists. Because multiple factors can contribute to resistant hypertension, an explicit, sequential approach to evaluation and management is essential to optimize blood pressure, reduce cardiorenal morbidity and mortality, and avoid unnecessary expense. A number of observational studies have suggested the potential efficacy of both spironolactone and amiloride when added to a 3 drug antihypertensive regimen, but to date no randomized study has directly compared the two agents. The goal of this study is to determine whether spironolactone or amiloride is the more effective fourth agent to add to a three drug regimen in patients with resistant hypertension.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: October 2010

Intervention(s) in this Clinical Trial

• Drug: spironolactone
  • tablet form. doses used range from 12.5-50mg po QDAY. Total duration would be until completion or study or medication intolerance.
• Drug: amiloride
  • amiloride 2.5-10 mg po QDAY. Duration until completion of study or until tolerance

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • this arm will include patients with resistant hypertension who are on 3 reasonably dosed agents (one being an appropriately dosed diuretic) and spironolactone will be added (dose range 12.5mg-50mg)
• Active Comparator: 2
  • this arm will include patients with resistant hypertension who are on 3 reasonably dosed agents (one being an appropriately dosed diuretic) and amiloride will be added (dose range 2.5-10mg)

Primary Measures

• Dose titration of spironolactone and amiloride will cease once the ABPM study reveals a goal 24 hour mean BP below 130/80 in the general hypertensive patients or below 120/70 in patients with diabetes mellitus or chronic kidney disease (eGFR < 60)
  • Time Frame: 2-6 months
    Safety Issue?: No

Inclusion Criteria:

• Participants will be selected from a broad range of medical clinics at the Salt Lake
• City VA Medical Center and surrounding community based outpatient clinics (CBOCs).
• The participants will be referred to a resistant hypertension clinic by either their primary care provider or by a subspecialist. The referrals are made via a computerized system that is used in the Veterans Affairs Medical Center (VA) called
• Computerized Patient Record System (CPRS).
• Patients are referred if their blood pressure is above goal as defined by JNC 7 and they are on 3 antihypertensive medications with one of the agents being a diuretic.
• All patients age 18 -80 years old.

Exclusion Criteria:

• Patients that will be excluded from the study if they have had a documented adverse reaction to either spironolactone or amiloride.
• diagnosis of primary hyperaldosteronism
• inability to adhere to frequent laboratory monitoring
• estimated glomerular filtration rate (GFR) < 45 ml/min/1.73m2
• baseline serum potassium above 5.0 mEq/L
• type 4 renal tubular acidosis
• pregnancy
• heart failure that meets criteria for using either eplerenone or spironolactone
• current unstable renal function

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: VA Salt Lake City Health Care System

Overall Clinical Trial Officials and Contacts

Richard S Rose, MD Principal Investigator Univ of Utah Division of General Internal Medicine; VAMC SLC Internal Medicine  

Overall Contact: Richard S Rose, MD 801-953-3004 richard.rose@hsc.utah.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00709137

Study ID Number: IRB_00027466

ClinicalTrials.gov Identifier: NCT00709137

Health Authority: United States: Federal Government