Spironolactone Versus Amiloride as an Add on Agent in Resistant Hypertension

This study has been withdrawn prior to enrollment.
(lack of enrollment)
Sponsor:
Information provided by (Responsible Party):
Richard Rose, VA Salt Lake City Health Care System
ClinicalTrials.gov Identifier:
NCT00709137
First received: July 1, 2008
Last updated: May 27, 2014
Last verified: May 2014
  Purpose

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 Intervention
Hypertension
Drug: spironolactone
Drug: amiloride

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Trial of Spironolactone Versus Amiloride as an Add on Agent in Resistant Hypertension

Resource links provided by NLM:


Further study details as provided by VA Salt Lake City Health Care System:

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) [ Time Frame: 2-6 months ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: October 2008
Study Completion Date: November 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

m/a

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00709137

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

Publications:
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
Study First Received: July 1, 2008
Last Updated: May 27, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by VA Salt Lake City Health Care System:
resistant hypertensions
spironolactone
amiloride
ambulatory blood pressure monitoring

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

ClinicalTrials.gov processed this record on August 20, 2014