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Spironolactone Versus Amiloride as an Add on Agent in Resistant Hypertension

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ClinicalTrials.gov Identifier: NCT00709137
Recruitment Status : Withdrawn (lack of enrollment)
First Posted : July 3, 2008
Last Update Posted : May 28, 2014
Information provided by (Responsible Party):

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
Hypertension Drug: spironolactone Drug: amiloride

Detailed Description:

Study Design

Study Type : Interventional  (Clinical Trial)
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 : October 2008
Primary Completion Date : October 2010
Study Completion Date : November 2010

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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 Name: 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 Name: midamor

Outcome Measures

Primary Outcome Measures :
  1. 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 ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00709137

United States, Utah
VAMC SLC - George Wahlen VA
SLC, Utah, United States, 84148
Sponsors and Collaborators
VA Salt Lake City Health Care System
Principal Investigator: Richard S Rose, MD Univ of Utah Division of General Internal Medicine; VAMC SLC Internal Medicine
More Information

Responsible Party: Richard Rose, Assistant Professor, VA Salt Lake City Health Care System
ClinicalTrials.gov Identifier: NCT00709137     History of Changes
Other Study ID Numbers: IRB_00027466
First Posted: July 3, 2008    Key Record Dates
Last Update Posted: May 28, 2014
Last Verified: May 2014

Keywords provided by Richard Rose, VA Salt Lake City Health Care System:
resistant hypertensions
ambulatory blood pressure monitoring

Additional relevant MeSH terms:
Vascular Diseases
Cardiovascular Diseases
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Natriuretic Agents
Acid Sensing Ion Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Epithelial Sodium Channel Blockers