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Spironolactone Versus Amiloride as an Add on Agent in Resistant Hypertension

Information source: VA Salt Lake City Health Care System
Information obtained from ClinicalTrials.gov on October 04, 2010
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Resistant Hypertension

Intervention: spironolactone (Drug); amiloride (Drug)

Phase: N/A

Status: Not yet recruiting

Sponsored by: VA Salt Lake City Health Care System

Official(s) and/or principal investigator(s):
Richard S Rose, MD, Principal Investigator, Affiliation: Univ of Utah Division of General Internal Medicine; VAMC SLC Internal Medicine

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


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.

Clinical Details

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

Study design: Allocation: Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 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)


Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.


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

Locations and Contacts

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

VAMC SLC - George Wahlen VA, SLC, Utah 84148, United States
Additional Information

Related publications:

Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, White A, Cushman WC, White W, Sica D, Ferdinand K, Giles TD, Falkner B, Carey RM; American Heart Association Professional Education Committee. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008 Jun 24;117(25):e510-26.

Moser M, Setaro JF. Clinical practice. Resistant or difficult-to-control hypertension. N Engl J Med. 2006 Jul 27;355(4):385-92. Review. No abstract available.

Nishizaka MK, Zaman MA, Calhoun DA. Efficacy of low-dose spironolactone in subjects with resistant hypertension. Am J Hypertens. 2003 Nov;16(11 Pt 1):925-30.

Lane DA, Shah S, Beevers DG. Low-dose spironolactone in the management of resistant hypertension: a surveillance study. J Hypertens. 2007 Apr;25(4):891-4.

Lane DA, Beevers DG. Amiloride 10 mg is less effective than spironolactone 25 mg in patients with hypertension resistant to a multidrug regime including an angiotensin-blocking agent. J Hypertens. 2007 Dec;25(12):2515-6. No abstract available.

Starting date: October 2008
Last updated: July 2, 2008

Page last updated: October 04, 2010

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