Can Nebivolol Reverse Inappropriate Left Ventricular Mass in Hypertensive Patients?

• Sponsor: Mayo Clinic (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01605370
• Collaborator: Forest Laboratories (Industry)
• Enrollment: 1
• Location: 1
• Arms: 2
• Duration (Months): 9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate if a drug called nebivolol can reverse inappropriate left ventricular mass (LVM) when compared to the standard of care drug metoprolol.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Nebivolol; Drug: Metoprolol succinate	Phase 4

Detailed Description

In response to chronic pressure overload by arterial hypertension, the cardiac left ventricle undergoes hypertrophy, that is, increases its wall thickness and, therefore, its mass, to sustain the elevated workload. Such anatomical remodeling can be considered adaptive or appropriate. However, in a considerable number of patients with arterial hypertension, the increase in the left ventricular mass is excessive and, thus, inappropriate.

Ventricular mass is inappropriate when its amount surpasses the physical need of the ventricle to sustain the elevated workload. Therefore, ventricular mass can be inappropriate even in patients without arterial hypertension or without hypertrophy identified by echocardiography (echo). We can mathematically predict an appropriate amount of mass and observe the actual mass in individual patients based on ventricular workload and wall thickness, respectively, noninvasively evaluated by echo. By comparing the observed ventricular mass to the predicted one, we determine whether its amount is inappropriate. It follows that by therapeutically normalizing blood pressure in hypertension and thus eliminating the elevated workload, then any ventricular hypertrophy represents an inappropriate mass.

Inappropriate ventricular mass is proven to have a detrimental effect on long-term cardiovascular event-free survival, and ventricular hypertrophy is increasingly recognized as a potent risk factor of cardiovascular morbidity and mortality, and all-cause mortality. Ventricular performance is altered in hypertension with inappropriate mass, but this alteration can be subtle enough to escape detection using current echocardiography measures. Hence, patients with hypertension, who have inappropriate left ventricular mass, need to be specifically identified by analysis of the predicted and observed ventricular mass, and the therapeutic goal must include management of elevated blood pressure as well as reversal of the excessive ventricular mass.

In this double-blind prospective study, patients with hypertension and inappropriate ventricular mass will be randomized to therapy with nebivolol or metoprolol to find out whether nebivolol could reverse inappropriate left ventricular mass, thus providing a benefit beyond what is achieved by mere blood pressure reduction alone. If confirmed, this will represent a significant ancillary ability of nebivolol and be a key step towards therapy of inappropriate ventricular mass, which is a so far unmanaged cardiovascular risk and a poor event-free prognostic factor.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: Can Nebivolol Reverse Inappropriate Left Ventricular Mass in Hypertensive Patients?
• Study Start Date: Jun 1, 2012
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nebivolol Subjects randomized to this arm will receive Nebivolol 2.5 mg once daily.	Drug: Nebivolol; Nebivolol 2.5 mg once daily; Other Names: Bystolic
Other: Metoprolol succinate Subjects randomized to this arm will receive metoprolol succinate 50 mg once daily.	Drug: Metoprolol succinate; Metoprolol succinate 50 mg once daily; Other Names: Toprol XL

Outcome Measures

Primary Outcome Measures

1. Change in Inappropriate Left Ventricular Mass (LVM) [baseline, 6 months]

   LVM will be measured by echocardiography exam. LVM is inappropriate when observed LVM (oLVM) exceeds predicted LVM (pLVM) by more than 28%, that is, 100×(oLVM/pLVM) >128%.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

All candidates must have previously untreated hypertension. The candidates will be picked from patients with stage-1 hypertension (systolic BP 140-159 mm Hg or diastolic BP 90-99 mm Hg) and those with stage-2 hypertension (systolic BP ≥160 mm Hg or diastolic BP ≥100), based on the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines (JNC-7).

Inclusion Criteria:

• Presence of inappropriate LVM.

• Presence of phenotype of inappropriate LVM.

Exclusion Criteria:

The criteria will assure that only patients with hypertension are enrolled, that is, excluded will be subjects with systolic BP < 140 or diastolic BP < 90 (ie, prehypertension or normal BP), but without complications or any indication (or suspicion) of end-organ damage based on a physical exam, clinical history, or laboratory tests.

Specific exclusion criteria are:

• Reactive airways disease including asthma.

• Diabetes mellitus or hypoglycemia; thyrotoxicosis.

• LV dysfunction (ejection fraction < 50%) or heart failure.

• Present or previously documented coronary heart disease or angina.

• Acute myocardial infarction, or history of myocardial infarction.

• Severe bradycardia, heart block greater than first degree or sick sinus syndrome (unless a permanent pacemaker is in place).

• Hepatic insufficiency or history of cirrhosis.

• Chronic renal failure or renovascular dysfunction.

• Cerebrovascular dysfunction.

• Peripheral vascular disease.

• Pregnant or nursing women; women of childbearing age will be required to take a pregnancy test at the time of enrollment and use an acceptable method of birth control.

• Poor echo image quality.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Arizona	Scottsdale	Arizona	United States	85259

Sponsors and Collaborators

• Mayo Clinic
• Forest Laboratories

Investigators

• Principal Investigator: Marek Belohlavek, MD, PhD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Marek Belohlavek, MD, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01605370
• Other Study ID Numbers: 11-007035
• First Posted: May 24, 2012
• Last Update Posted: May 19, 2014
• Last Verified: May 1, 2014

• Keywords provided by Marek Belohlavek, MD, Mayo Clinic: Hypertension, Left Ventricular Mass
• Additional relevant MeSH terms: Hypertension; Metoprolol; Nebivolol

Study Results

Participant Flow

Arm/Group Title	Nebivolol	Metoprolol Succinate
Arm/Group Description	Subjects randomized to this arm will receive Nebivolol 2.5 mg once daily. Nebivolol: Nebivolol 2.5 mg once daily	Subjects randomized to this arm will receive metoprolol succinate 50 mg once daily. Metoprolol succinate: Metoprolol succinate 50 mg once daily
Period Title: Overall Study
STARTED	1	0
COMPLETED	0	0
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Nebivolol	Metoprolol Succinate	Total
Arm/Group Description	Subjects randomized to this arm will receive Nebivolol 2.5 mg once daily. Nebivolol: Nebivolol 2.5 mg once daily	Subjects randomized to this arm will receive metoprolol succinate 50 mg once daily. Metoprolol succinate: Metoprolol succinate 50 mg once daily	Total of all reporting groups
Overall Participants	1	0	1
Age (participants) [Number]
<=18 years	0 0%	0 NaN
Between 18 and 65 years	1 100%	1 Infinity
>=65 years	0 0%	0 NaN
Gender (participants) [Number]
Female	0 0%	0 NaN
Male	1 100%	1 Infinity
Region of Enrollment (participants) [Number]
United States	1 100%	1 Infinity

Outcome Measures

1. Primary Outcome

Title	Change in Inappropriate Left Ventricular Mass (LVM)
Description	LVM will be measured by echocardiography exam. LVM is inappropriate when observed LVM (oLVM) exceeds predicted LVM (pLVM) by more than 28%, that is, 100×(oLVM/pLVM) >128%.
Time Frame	baseline, 6 months

Outcome Measure Data

Analysis Population Description

Data were not collected for the single participant, so no analysis was performed.

Arm/Group Title	Nebivolol	Metoprolol Succinate
Arm/Group Description	Subjects randomized to this arm will receive Nebivolol 2.5 mg once daily. Nebivolol: Nebivolol 2.5 mg once daily	Subjects randomized to this arm will receive metoprolol succinate 50 mg once daily. Metoprolol succinate: Metoprolol succinate 50 mg once daily
Measure Participants	0	0

Adverse Events

Arm/Group Title	Nebivolol		Metoprolol Succinate
Arm/Group Description	Subjects randomized to this arm will receive Nebivolol 2.5 mg once daily. Nebivolol: Nebivolol 2.5 mg once daily		Subjects randomized to this arm will receive metoprolol succinate 50 mg once daily. Metoprolol succinate: Metoprolol succinate 50 mg once daily
All Cause Mortality
	Nebivolol		Metoprolol Succinate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Nebivolol		Metoprolol Succinate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Nebivolol		Metoprolol Succinate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		0/0 (NaN)
Respiratory, thoracic and mediastinal disorders
Wheezing	1/1 (100%)	1	0/0 (NaN)	0

Limitations/Caveats

The study was terminated early due to the difficulty in identifying subjects satisfying the inclusion criteria. Only 1 subject was enrolled.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.