Combined Renin Inhibition/Beta-blockade

NCT00627861 | Terminated Results

• 1 other identifier: 0712009564
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Antihypertensive drug treatment is effective in only about 50% of patients. One mechanism responsible for treatment failure is a drug related stimulation of the renin-angiotension-aldosterone-system (RAAS). Several classes of medications that treat hypertension by blocking the RAAS system have been developed. However, the kidney responds to these drug treatments by producing greater amounts of renin. This high level of renin can reduce the effectiveness of some of these medications, ultimately causing the blood pressure to rise. This is one reason why blood pressure can be difficult to control in a certain percentage of patients. The hypothesis to be tested in the proposed study is that beta-adrenergic blockade (β-blockade), when superimposed upon aliskiren, a drug that competitively inhibits plasma renin activity (PRA) but stimulates the release of renin by the kidneys (plasma renin concentration \[PRC\]), can suppress the reactive increase in PRC that occurs during aliskiren monotherapy. The primary aim of this study is to measure plasma renin concentration (PRC) and plasma renin activity (PRA) levels during renin inhibition with aliskiren and combined renin inhibition/β-blocker treatment to determine whether the addition of a β-blocker attenuates the rise in plasma renin concentration (PRC). A secondary aim is to determine whether combined treatment further suppresses PRA and blood pressure.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (1)

• Plasma Renin Concentration

  5th, 6th, 7th, 9th, 10th, 11th, 12th weeks

Secondary Outcomes (2)

• Plasma Renin Activity

  screening, 4th, 6th, 7th, 9th, 10th, 11th, 12th weeks

• Blood Pressure

  all visits (weekly for 12 weeks)

Study Arms (1)

Aliskiren and metoprolol succinate

EXPERIMENTAL

Drug: Aliskiren; Drug: Extended-release metoprolol

Interventions

Aliskiren DRUG

150mg orally daily for 6 weeks. Dose may increase to 300mg orally daily dependent upon blood pressure parameters set by the protocol.

Also known as: Tekturna

Aliskiren and metoprolol succinate

Extended-release metoprolol DRUG

50mg orally daily for 1 week, dose will increase to 100mg orally daily or decrease to 25mg daily for a second week dependent upon blood pressure parameters set by the protocol. Subjects will take metoprolol for a total of 2 weeks, then be tapered off of it over 5-7 days.

Also known as: Toprol-XL

Aliskiren and metoprolol succinate

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-80 years
• Stage 1 (systolic 140-159 mm Hg or diastolic 90-99 mmHg) or Stage 2 (systolic \>160 mm Hg or diastolic \>100 mmHg) or current treatment with antihypertensive medication.
• PRA ≥0.65 ng/ml/h. If PRA is below this level during the screening period, due to treatment with a beta-blocker or central α2-receptor agonist, the subject may be enrolled and the PRA level re-checked after treatment is tapered off.

You may not qualify if:

• History of diabetes requiring pharmacologic treatment with an oral or parenteral hypoglycemic agent, including insulin
• TIA, stroke or myocardial infarction
• History of asthma or COPD
• Cockcroft Gault estimated GFR \<60 ml/min/1.73 m2
• Previous adverse events during treatment with a β-blocker or aliskiren
• ALT level twice normal
• Secondary forms of hypertension (e.g., renovascular, primary aldosteronism)
• PRA\<0.65 ng/ml/h after discontinuation of antihypertensive medication
• Systolic BP\>180 mm Hg, diastolic BP\>105 mm Hg
• Pregnant or breastfeeding, or planning pregnancy during the study period

Sponsors & Collaborators

• The Rogosin Institute: lead

Study Sites (1)

The Rogosin Institute

New York, New York, 10021, United States

Location

Related Publications (5)

• Staessen JA, Li Y, Richart T. Oral renin inhibitors. Lancet. 2006 Oct 21;368(9545):1449-56. doi: 10.1016/S0140-6736(06)69442-7.

  PMID: 17055947 BACKGROUND

• Nussberger J, Wuerzner G, Jensen C, Brunner HR. Angiotensin II suppression in humans by the orally active renin inhibitor Aliskiren (SPP100): comparison with enalapril. Hypertension. 2002 Jan;39(1):E1-8. doi: 10.1161/hy0102.102293.

  PMID: 11799102 RESULT

• Sealey JE, Laragh JH. Aliskiren, the first renin inhibitor for treating hypertension: reactive renin secretion may limit its effectiveness. Am J Hypertens. 2007 May;20(5):587-97. doi: 10.1016/j.amjhyper.2007.04.001.

  PMID: 17485026 RESULT

• Oparil S, Yarows SA, Patel S, Fang H, Zhang J, Satlin A. Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial. Lancet. 2007 Jul 21;370(9583):221-229. doi: 10.1016/S0140-6736(07)61124-6.

  PMID: 17658393 RESULT

• Blumenfeld JD, Sealey JE, Mann SJ, Bragat A, Marion R, Pecker MS, Sotelo J, August P, Pickering TG, Laragh JH. Beta-adrenergic receptor blockade as a therapeutic approach for suppressing the renin-angiotensin-aldosterone system in normotensive and hypertensive subjects. Am J Hypertens. 1999 May;12(5):451-9. doi: 10.1016/s0895-7061(99)00005-9.

  PMID: 10342782 RESULT

MeSH Terms

Conditions

Hypertension

Interventions

aliskiren; Metoprolol

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Results Point of Contact

• Title: Warren Bobb, N.P.
• Organization: The Rogosin Institute

wab9006@nyp.org

212-746-9114

Study Officials

• Jon D Blumenfeld, M.D.

  The Rogosin Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2008
• First Posted: March 4, 2008
• Study Start: November 1, 2008
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: November 24, 2015
• Results First Posted: September 28, 2011

Record last verified: 2015-10

Locations

US (1)