HypertensionNCT00834600
Renin Profiling in Selection of Initial Antihypertensive Drug
A study testing olmesartan, hydrochlorothiazide, amlodipine and hydrochlorothiazide (HCTZ) or olmesartan in people with Hypertension, run by The Louis & Rachel Rudin Foundation at 5 sites in United States.
Trial summary
The purpose of this research study is to determine whether a simple blood test measuring a hormone called renin can better determine which first drug would be most effective in controlling blood pressure, in comparison with the more traditional approach recommended by JNC7 (Joint National Committee on Prevention… Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Hypertension
- What is being tested?
- olmesartan, hydrochlorothiazide, amlodipine and hydrochlorothiazide (HCTZ) or olmesartan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 185 participants
- Where
- 5 sitesUnited States
- Study dates
- Dec 2005to Oct 2011
- 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 40 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females, 40 to 85 years of age
- Sustained systolic blood pressure between 140-180 mm Hg
- Free of antihypertensive therapy at randomization for at least 4 weeks
Who cannot join
- Ages <40, or >85 years
- Systolic blood pressure >180 mm Hg
- Blood pressure >180/105 mm Hg during the washout period
- Require antihypertensive agents for non-blood pressure indications
- Taking clonidine
- On a beta-blocker drug and have known or suspected coronary artery disease
Show all 14Show fewer
- Documented history of a heart attack, new onset of chest pain, or a coronary revascularization procedure within the past year, congestive heart failure
- Serious intercurrent illness
- An active ulcer
- Have certain abnormal laboratory tests (elevated serum creatinine >1.5 mg/dl, transaminase > 2 times upper limit of normal or active liver disease),
- Hypersensitivity, allergy or have an intolerance to angiotensin II receptor blockers (olmesartan), hydrochlorothiazide or amlodipine
- Mentally or legally unable to participate
- Have or are currently abusing alcohol, have abused drugs within the past 2 years
- Have been in another drug study in the past month.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Lincoln Medical and Mental Health Center
The Bronx, New York, 10451
Albert Einstein College of Medicine - GCRC
The Bronx, New York, 10461
Jacobi Medical Center
The Bronx, New York, 10461
Bronx Nephrology Hypertension, PC
The Bronx, New York, 10467
Ralph Yung, MD
The Bronx, New York, 10467
About this study
Official title: A Clinical Trial of Renin Profiling in Selection of Initial Antihypertensive Drug
The purpose of this research study is to determine whether a simple blood test measuring a hormone called renin can better determine which first drug would be most effective in controlling blood pressure, in comparison with the more traditional approach recommended by JNC7 (Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure).
Read the detailed description
Hypothesis: That antihypertensive drug selection guided by activity of the renin angiotensin system will be superior to the strategy advocated in JNC 7 in achieving blood pressure control on monotherapy.
Background: the National Heart, Lung, and Blood Institute, through the Joint National Committee on the Detection, Treatment and Control of Hypertension (JNC 7) has recommended that most hypertensive patients begin therapy with a diuretic and sequentially add other classes of drugs until blood pressure is controlled. This approach appears to assume homogeneity in the mechanism by which BP is controlled in different patients. When this standardized strategy has been rigidly applied in Clinical Trials, a majority of patients generally require 2 or more agents to achieve blood pressure control.
The pioneering work of Laragh, Sealey and their colleagues, widely confirmed by others, suggests instead that heterogeneity, in fact, characterizes patterns of blood pressure control in populations. This heterogeneity can be exposed through assessment of the activity of the renin angiotensin system (RAS). Specifically, volume and vasoconstriction determine blood pressure control. Patients in whom volume predominates have suppressed RAS, and, conversely, those in whom vasoconstriction predominates will have an activated RAS. This can be simply and accurately determined by estimation of plasma renin activity (PRA).
It has been demonstrated that volume and vasoconstriction dependent hypertensive patients respond best to different drugs. By exploitation of the RAS it is possible to provide rational therapy to each patients according to the mechanism by which blood pressure is controlled. The result is that appropriate therapy can be both more effective and more efficient. A specific system the Laragh Method has been designed to translate this physiologically based paradigm into a practical scheme or patient management.
The purpose of this trial is to determine whether the Laragh Method will lead to better and more efficient blood pressure control in a general population of hypertensive patients than does the existing treatment strategy. The measure by which this hypothesis will be tested is percentage of hypertensive patients achieving blood pressure control on monotherapy.
The significance of this trial is enormous for both individuals and society. Some 50 million Americans have hypertension and more than 25 million are currently in treatment. If the Laragh Method leads to more parsimonious and effective care, it will mean literally millions of individual patients will be spared the burden of unnecessary polypharmacy. Moreover, the strain on health care costs associated with antihypertensive therapy will be redu
- Conditions
- Hypertension
- Being tested
- olmesartan, hydrochlorothiazide, amlodipine, hydrochlorothiazide (HCTZ) or olmesartan
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
olmesartan, hydrochlorothiazide, amlodipineDrug
Also called Renin guided selection of treatment
hydrochlorothiazide (HCTZ) 25mg OD, increased to 50 mg OD at 3 weeks. Olmesartan 20 mg OD, to be increased to 40 mg at 3 weeks. Amlodipine 5 mg, may be added at 6 weeks, if BP >140 mmHg
hydrochlorothiazide (HCTZ) or olmesartanDrug
Also called Standard Therapy
HCTZ 25 mg, increasing to 50 mg at 3-4 weeks or Olmesartan 20 mg, increasing to 40 mg at 3-4 weeks. If blood pressure >140/90 mmHg at 6 weeks, amlodipine 5 mg may be added
| Study group | Role | What they receive |
|---|---|---|
| HCTZ , ARB | Experimental | Patients randomized to the Experimental Arm have initial drug choice determined by Plasma Renin Activity level. Low renin subjects are assigned to the diuretic hydrochlorothothiazide. Those with PRA >.65 ng/hr are assigned to the angiotensin receptor blocker, olmesartan. Receives: Drug: olmesartan, hydrochlorothiazide, amlodipine; Drug: hydrochlorothiazide (HCTZ) or olmesartan |
| Conventional antihypertensive therapy | Active comparator | All patients randomized to Active Comparator Arm received hydrochlorothiazide 25 mg, which is increased to 50 mg at 3-4 weeks. At 6 weeks, olmesartan may be added if BP > 140 mmHg Receives: Drug: olmesartan, hydrochlorothiazide, amlodipine; Drug: hydrochlorothiazide (HCTZ) or olmesartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of patients with BP <140/90 mmHg and on monotherapy at the 5th visit.
Measured: 3-4 months
Secondary outcomes (2)
Will include change in blood pressure, percent of patients with blood pressure <140/mmHg, total number of classes of antihypertensive agents taken, adverse events and discontinuation of therapy.
Measured: 3-4 months
In addition, we will be able to determine the reproducibility of PRA determination in this clinical setting. Finally, it will be possible to demonstrate the value of "in-treatment" PRA as a guide to treatment modification.
Measured: 3-4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2009 (estimated)
- Study startDec 2005
- Primary completionOct 2011
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 185 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Louis & Rachel Rudin Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- Daiichi Sankyo
- Responsible party
- Principal investigator, Michael H. Alderman, The Louis & Rachel Rudin Foundation
- Investigators
- Michael H Alderman, M.D., Principal investigator, Albert Einstein College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00834600
- Sponsor's protocol ID
- 04-074
- Other IDs
- MMC #05-02-054
- Status last verified
- Oct 2010
- First submitted
- 30 Jan 2009
- Last updated
- 19 Apr 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003 Dec;42(6):1206-52. doi: 10.1161/01.HYP.0000107251.49515.c2. Epub 2003 Dec 1.
PubMed 14656957Laragh JH: Laragh's Lessons in Renin System Pathophysiology for Treating Hypertension and its Fatal Cardiovascular Consequences. Elsevier Science Inc.,2002,N.Y.
Laragh JH, Sealey JE. Renin system understanding for analysis and treatment of hypertensive patients: a means to quantify the vasoconstrictor elements, diagnose curable renal and adrenal causes, assess risk of cardiovascular morbidity, and find the best-fit drug regimen. Chapter 107, In: Hypertension:Pathophysiology Diagnosis and Management, 2nd Edition, Edited by JH Laragh and BM Brunner. Raven Press,Ltd.,New York 1995.
Sealey JE. Measurement of the hormones of the renin system in hypertensive patients. Clin Biochem. 1981 Oct;14(5):273-81. doi: 10.1016/s0009-9120(81)91000-6. No abstract available.
PubMed 6120769
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Trial of Renin Profiling in Selection of Initial Antihypertensive Drug
- ClinicalTrials.gov ID
- NCT00834600
- Acronym / sponsor ID
- 04-074
- Conditions
- Hypertension
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 185 participants (actual)
- Lead sponsor
- The Louis & Rachel Rudin FoundationUniversity, hospital or other
- Collaborators
- Daiichi Sankyo
- Study start
- Dec 2005
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 3 Feb 2009 (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.
The purpose of this research study is to determine whether a simple blood test measuring a hormone called renin can better determine which first drug would be most effective in controlling blood pressure, in comparison with the more traditional approach recommended by JNC7 (Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure).
Detailed description
Hypothesis: That antihypertensive drug selection guided by activity of the renin angiotensin system will be superior to the strategy advocated in JNC 7 in achieving blood pressure control on monotherapy.
Background: the National Heart, Lung, and Blood Institute, through the Joint National Committee on the Detection, Treatment and Control of Hypertension (JNC 7) has recommended that most hypertensive patients begin therapy with a diuretic and sequentially add other classes of drugs until blood pressure is controlled. This approach appears to assume homogeneity in the mechanism by which BP is controlled in different patients. When this standardized strategy has been rigidly applied in Clinical Trials, a majority of patients generally require 2 or more agents to achieve blood pressure control.
The pioneering work of Laragh, Sealey and their colleagues, widely confirmed by others, suggests instead that heterogeneity, in fact, characterizes patterns of blood pressure control in populations. This heterogeneity can be exposed through assessment of the activity of the renin angiotensin system (RAS). Specifically, volume and vasoconstriction determine blood pressure control. Patients in whom volume predominates have suppressed RAS, and, conversely, those in whom vasoconstriction predominates will have an activated RAS. This can be simply and accurately determined by estimation of plasma renin activity (PRA).
It has been demonstrated that volume and vasoconstriction dependent hypertensive patients respond best to different drugs. By exploitation of the RAS it is possible to provide rational therapy to each patients according to the mechanism by which blood pressure is controlled. The result is that appropriate therapy can be both more effective and more efficient. A specific system the Laragh Method has been designed to translate this physiologically based paradigm into a practical scheme or patient management.
The purpose of this trial is to determine whether the Laragh Method will lead to better and more efficient blood pressure control in a general population of hypertensive patients than does the existing treatment strategy. The measure by which this hypothesis will be tested is percentage of hypertensive patients achieving blood pressure control on monotherapy.
The significance of this trial is enormous for both individuals and society. Some 50 million Americans have hypertension and more than 25 million are currently in treatment. If the Laragh Method leads to more parsimonious and effective care, it will mean literally millions of individual patients will be spared the burden of unnecessary polypharmacy. Moreover, the strain on health care costs associated with antihypertensive therapy will be redu
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HCTZ , ARB | Experimental | Drug: olmesartan, hydrochlorothiazide, amlodipine, Drug: hydrochlorothiazide (HCTZ) or olmesartanPatients randomized to the Experimental Arm have initial drug choice determined by Plasma Renin Activity level. Low renin subjects are assigned to the diuretic hydrochlorothothiazide. Those with PRA >.65 ng/hr are assigned to the angiotensin receptor blocker, olmesartan. |
| Conventional antihypertensive therapy | Active comparator | Drug: olmesartan, hydrochlorothiazide, amlodipine, Drug: hydrochlorothiazide (HCTZ) or olmesartanAll patients randomized to Active Comparator Arm received hydrochlorothiazide 25 mg, which is increased to 50 mg at 3-4 weeks. At 6 weeks, olmesartan may be added if BP > 140 mmHg |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Males and females, 40 to 85 years of age
- Sustained systolic blood pressure between 140-180 mm Hg
- Free of antihypertensive therapy at randomization for at least 4 weeks
Key exclusion criteria (14 listed)
- Ages <40, or >85 years
- Systolic blood pressure >180 mm Hg
- Blood pressure >180/105 mm Hg during the washout period
- Require antihypertensive agents for non-blood pressure indications
- Taking clonidine
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 |
|---|---|---|
| olmesartan, hydrochlorothiazide, amlodipineAlso: Renin guided selection of treatmenthydrochlorothiazide (HCTZ) 25mg OD, increased to 50 mg OD at 3 weeks. Olmesartan 20 mg OD, to be increased to 40 mg at 3 weeks. Amlodipine 5 mg, may be added at 6 weeks, if BP >140 mmHg | Drug | Conventional antihypertensive therapy, HCTZ , ARB |
| hydrochlorothiazide (HCTZ) or olmesartanAlso: Standard TherapyHCTZ 25 mg, increasing to 50 mg at 3-4 weeks or Olmesartan 20 mg, increasing to 40 mg at 3-4 weeks. If blood pressure >140/90 mmHg at 6 weeks, amlodipine 5 mg may be added | Drug | Conventional antihypertensive therapy, HCTZ , ARB |
Primary outcome
Percent of patients with BP <140/90 mmHg and on monotherapy at the 5th visit.
Time frame: 3-4 months
2 secondary outcomes
Will include change in blood pressure, percent of patients with blood pressure <140/mmHg, total number of classes of antihypertensive agents taken, adverse events and discontinuation of therapy.
Time frame: 3-4 months
In addition, we will be able to determine the reproducibility of PRA determination in this clinical setting. Finally, it will be possible to demonstrate the value of "in-treatment" PRA as a guide to treatment modification.
Time frame: 3-4 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2012.
- Background: PubMed 14656957Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003 Dec;42(6):1206-52. doi: 10.1161/01.HYP.0000107251.49515.c2. Epub 2003 Dec 1.
- BackgroundLaragh JH: Laragh's Lessons in Renin System Pathophysiology for Treating Hypertension and its Fatal Cardiovascular Consequences. Elsevier Science Inc.,2002,N.Y.
- BackgroundLaragh JH, Sealey JE. Renin system understanding for analysis and treatment of hypertensive patients: a means to quantify the vasoconstrictor elements, diagnose curable renal and adrenal causes, assess risk of cardiovascular morbidity, and find the best-fit drug regimen. Chapter 107, In: Hypertension:Pathophysiology Diagnosis and Management, 2nd Edition, Edited by JH Laragh and BM Brunner. Raven Press,Ltd.,New York 1995.
- Background: PubMed 6120769Sealey JE. Measurement of the hormones of the renin system in hypertensive patients. Clin Biochem. 1981 Oct;14(5):273-81. doi: 10.1016/s0009-9120(81)91000-6. 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.
Michael H Alderman, M.D. principal investigator
Albert Einstein College of Medicine
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing olmesartan, hydrochlorothiazide, amlodipine and hydrochlorothiazide (HCTZ) or olmesartan in people with Hypertension, run by The Louis & Rachel Rudin Foundation at 5 sites 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 3 inclusion and 14 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: finished, as of the sponsor's last update on 19 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Percent of patients with BP <140/90 mmHg and on monotherapy at the 5th visit. (time frame: 3-4 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 NCT00834600, which also lists 4 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 19 Apr 2012.