Spironolactone Versus Amiloride as an Add on Agent in Resistant Hypertension

May 27, 2014 updated by: Richard Rose, VA Salt Lake City Health Care System

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

m/a

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Utah
      • SLC, Utah, United States, 84148
        • VAMC SLC - George Wahlen VA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
2-6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2008

Primary Completion (ACTUAL)

October 1, 2010

Study Completion (ACTUAL)

November 1, 2010

Study Registration Dates

First Submitted

July 1, 2008

First Submitted That Met QC Criteria

July 2, 2008

First Posted (ESTIMATE)

July 3, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

May 28, 2014

Last Update Submitted That Met QC Criteria

May 27, 2014

Last Verified

May 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB_00027466

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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