Spironolactone Versus Amiloride as an Add on Agent in Resistant Hypertension

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00709137
• Other study ID #: IRB_00027466
• Status: Withdrawn
• Phase: N/A
• First received: July 1, 2008
• Last updated: May 27, 2014
• Start date: October 2008
• Est. completion date: November 2010

Study information

• Verified date: May 2014
• Source: VA Salt Lake City Health Care System
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Description:

m/a

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Hypertension

Intervention

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

Locations

Country	Name	City	State
United States	VAMC SLC - George Wahlen VA	SLC	Utah

Sponsors (1)

Lead Sponsor	Collaborator
VA Salt Lake City Health Care System

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. doi: 10.1161/CIRCULATIONAHA.108.189141. — View Citation

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. — View Citation

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. — View Citation

Moser M, Setaro JF. Clinical practice. Resistant or difficult-to-control hypertension. N Engl J Med. 2006 Jul 27;355(4):385-92. Review. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)		2-6 months	No