HypertensionNCT00709137
Spironolactone Versus Amiloride as an Add on Agent in Resistant Hypertension
A study testing spironolactone and amiloride in people with Hypertension, run by VA Salt Lake City Health Care System at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypertension
- What is being tested?
- spironolactone and amiloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2008to Nov 2010
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- pregnancy
- heart failure that meets criteria for using either eplerenone or spironolactone
- current unstable renal function
Trial locations and contacts
1 site in 1 country.
United States1 site
VAMC SLC - George Wahlen VA
Salt Lake City, Utah, 84148
About this study
Official title: 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.
Read the detailed description
m/a
- Conditions
- Hypertension
- Being tested
- spironolactone, amiloride
- Keywords
- resistant hypertensions, spironolactone, amiloride, ambulatory blood pressure monitoring
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
spironolactoneDrug
Also called aldactone
tablet form. doses used range from 12.5-50mg po QDAY. Total duration would be until completion or study or medication intolerance.
amilorideDrug
Also called midamor
amiloride 2.5-10 mg po QDAY. Duration until completion of study or until tolerance
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Drug: amiloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 2-6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2008 (estimated)
- Study startOct 2008
- Primary completionOct 2010
- Study completionNov 2010
Why it stopped: lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Salt Lake City Health Care System
- Sponsor type
- US federal agency
- Responsible party
- Principal investigator, Richard Rose, VA Salt Lake City Health Care System
- Investigators
- Richard S Rose, MD, Principal investigator, Univ of Utah Division of General Internal Medicine; VAMC SLC Internal Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00709137
- Sponsor's protocol ID
- IRB_00027466
- Status last verified
- May 2014
- First submitted
- 1 Jul 2008
- Last updated
- 28 May 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 18574054Moser 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.
PubMed 16870917Nishizaka 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.
PubMed 14573330Lane 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.
PubMed 17351384Lane 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.
PubMed 17984678
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Spironolactone Versus Amiloride as an Add on Agent in Resistant Hypertension
- ClinicalTrials.gov ID
- NCT00709137
- Acronym / sponsor ID
- IRB_00027466
- Conditions
- Hypertension
- Keywords
- resistant hypertensions, spironolactone, amiloride, ambulatory blood pressure monitoring
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: lack of enrollment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- VA Salt Lake City Health Care SystemUS federal agency
- Study start
- Oct 2008
- Primary completion
- Oct 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 3 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
m/a
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: spironolactonethis 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) |
| 2 | Active comparator | Drug: amiloridethis 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) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| spironolactoneAlso: aldactonetablet form. doses used range from 12.5-50mg po QDAY. Total duration would be until completion or study or medication intolerance. | Drug | 1 |
| amilorideAlso: midamoramiloride 2.5-10 mg po QDAY. Duration until completion of study or until tolerance | Drug | 2 |
Primary outcome
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2014.
- Background: PubMed 18574054Calhoun 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.
- Background: PubMed 16870917Moser 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.
- Background: PubMed 14573330Nishizaka 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.
- Background: PubMed 17351384Lane 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.
- Background: PubMed 17984678Lane 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard S Rose, MD principal investigator
Univ of Utah Division of General Internal Medicine; VAMC SLC Internal Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing spironolactone and amiloride in people with Hypertension, run by VA Salt Lake City Health Care System at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 28 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00709137, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2014.