Spironolactone Versus Amiloride as an Add on Agent in Resistant Hypertension

NCT00709137 | Withdrawn DMC

• 1 other identifier: IRB_00027466
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension

Keywords

resistant hypertensions; spironolactone; amiloride; ambulatory blood pressure monitoring

Outcome Measures

Primary Outcomes (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)

  2-6 months

Study Arms (2)

1

ACTIVE COMPARATOR

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

2

ACTIVE COMPARATOR

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

Interventions

spironolactone DRUG

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

Also known as: aldactone

1

amiloride DRUG

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

Also known as: midamor

2

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Salt Lake City Health Care System: lead

Study Sites (1)

VAMC SLC - George Wahlen VA

Salt Lake City, Utah, 84148, United States

Location

Related 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.

  PMID: 18574054 BACKGROUND

• Moser M, Setaro JF. Clinical practice. Resistant or difficult-to-control hypertension. N Engl J Med. 2006 Jul 27;355(4):385-92. doi: 10.1056/NEJMcp041698. No abstract available.

  PMID: 16870917 BACKGROUND

• 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. doi: 10.1016/s0895-7061(03)01032-x.

  PMID: 14573330 BACKGROUND

• 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. doi: 10.1097/HJH.0b013e328014954d.

  PMID: 17351384 BACKGROUND

• 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. doi: 10.1097/HJH.0b013e3282f254d9. No abstract available.

  PMID: 17984678 BACKGROUND

MeSH Terms

Conditions

Hypertension

Interventions

Spironolactone; Amiloride

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Richard S Rose, MD

  Univ of Utah Division of General Internal Medicine; VAMC SLC Internal Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 1, 2008
• First Posted: July 3, 2008
• Study Start: October 1, 2008
• Primary Completion: October 1, 2010
• Study Completion: November 1, 2010
• Last Updated: May 28, 2014

Record last verified: 2014-05

Locations

US (1)