Spironolactone Versus Amiloride as an Add on Agent in Resistant Hypertension

Sponsor

VA Salt Lake City Health Care System (U.S. Fed)

Overall Status

Withdrawn

CT.gov ID

NCT00709137

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: spironolactone Drug: amiloride	N/A

Detailed Description

m/a

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2008

Actual Primary Completion Date :

Oct 1, 2010

Actual Study Completion Date :

Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
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)	Drug: spironolactone tablet form. doses used range from 12.5-50mg po QDAY. Total duration would be until completion or study or medication intolerance. Other Names: aldactone
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)	Drug: amiloride amiloride 2.5-10 mg po QDAY. Duration until completion of study or until tolerance Other Names: midamor

Arm

Intervention/Treatment

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)

Drug: spironolactone

tablet form. doses used range from 12.5-50mg po QDAY. Total duration would be until completion or study or medication intolerance.

Other Names:

aldactone

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)

Drug: amiloride

amiloride 2.5-10 mg po QDAY. Duration until completion of study or until tolerance

Other Names:

midamor

Outcome Measures

Primary Outcome 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) [2-6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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