24 Hour Ambulatory Cardiac Oxygen Consumption

Hypertension Clinical Trial

Official title:

Ambulatory 24-Hour Cardiac Oxygen Consumption and Blood Pressure-Heart Rate Variability: Effects of Nebivolol and Valsartan Alone and in Combination

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05170061
• Other study ID #: BYS-IT-76
• Status: Completed
• Phase: Phase 3
• Start date: February 2013
• Est. completion date: December 2014

Study information

• Verified date: December 2021
• Source: State University of New York at Buffalo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A randomized,double-blind,double-dummy,active controlled,15 week study to evaluate the effects of nebivolol and valsartan alone and in combination on 24-hour ambulatory cardiac work and variability of heart rate-mean central systolic pressure product.

Description:

Subjects with hypertension (systolic blood pressure (SBP) >140 or diastolic blood pressure (DBP)>90, n=26) were studied using a double-blinded, forced-titration, sequence-controlled, crossover design with 3 experimental periods: Valsartan 320, nebivolol 40, and nebivolol/valsartan 320/40 mg daily. After 4 weeks of each drug, ambulatory pulse wave analysis (IEM MobilOGraph) was performed every 20 min for 24-hours. The primary hypothesis was that nebivolol/valsartan combination therapy would be superior to valsartan monotherapy in reducing mean 24-hour mean myocardial oxygen consumption determined by 24-hour ambulatory heart rate-central systolic pressure product [ACRPP]. A secondary hypothesis was that the combination would also reduce the variability of 24-hour myocardial oxygen consumption.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: December 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects with chronic hypertension, treated or untreated

• Males and females, 18 years or older

• Seated clinic systolic BP 145-184 mmHg inclusive or

• Seated clinic diastolic BP 92-119 mmHg, inclusive.

Exclusion Criteria:

• Subjects with any of the following conditions will be excluded:

• Any acute or chronic medical condition that, in the judgment of the investigator, renders the subject unable to complete the study, would interfere with optimal participation in the study, or cause significant risk to the subject

• Concomitant or probable need for treatment with other cardiovascular or antihypertensive drugs that may affect blood pressure or influence the effects of study drugs, (e.g. NSAIDs, beta-agonist inhalers therapy for bronchospastic asthma, diuretics); other stable chronic medications that have little effect on study drugs (e.g. diabetes medications, hormone replacements, chronic pain medications. osteoporosis drugs, vitamins, cholesterol drugs, etc.) are permitted if continued at stable doses throughout study.

• History of clinically significant adverse events with beta-blocker or angiotensin-receptor blocker

• Known or suspected secondary hypertension (e.g., renovascular hypertension, primary hyperaldosteronism, etc.)

• Known ischemic heart disease requiring continuous beta-blocker therapy (includes angina, prior transmural myocardial infarction, coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty or stenting within 6 months prior to study entry).

• Dilated cardiomyopathy (NYHA Functional Class III-IV)

• Clinically significant valvular heart disease or obstructive hypertrophic cardiomyopathy

• Presence of clinically significant ventricular or supraventricular arrhythmias (e.g. atrial fibrillation/flutter), pre-excitation syndrome, second or third degree atrioventricular block, other conduction defects necessitating the implantation of a permanent cardiac pacemaker, or sick sinus syndrome.

• Chronic kidney disease (serum creatinine >2.5 mg/dL)

• Uncontrolled diabetes mellitus (hemoglobin A1c > 10%)

• History of alcohol or other drug abuse within 6 months prior to enrollment

• Positive pregnancy test or failure to practice adequate contraception in women of child-bearing potential

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Valsartan
Valsartan 160 mg PO daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1 week down-titration to 160 mg daily
• Nebivolol
Nebivolol 20 mg daily for 1 week followed by 40 mg daily for 3 weeks, followed by 1 week down-titration to 20 mg daily
• Nebivolol/valsartan
Valsartan/Nebivolol, 160/20 mg daily for 1 week followed by 320/40 mg daily for 3 weeks, followed by 1 week down-titration to 160/20 mg daily

Locations

Country	Name	City	State
United States	Erie County Medical Center	Buffalo	New York

Sponsors (1)

Lead Sponsor	Collaborator
State University of New York at Buffalo

Country where clinical trial is conducted

United States, 

References & Publications (1)

Izzo JL Jr, Khan SU, Saleem O, Osmond PJ. Ambulatory 24-hour cardiac oxygen consumption and blood pressure-heart rate variability: effects of nebivolol and valsartan alone and in combination. J Am Soc Hypertens. 2015 Jul;9(7):526-35. doi: 10.1016/j.jash.2 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	24-hour myocardial oxygen consumption	Determined by 24-hour ambulatory heart rate-central systolic pressure product [ACRPP] at the end of each study phase (units)	15 weeks
Primary	Standard deviation of 24-hour myocardial oxygen consumption	Standard deviation of ACRPP	15 weeks
Secondary	Clinical peripheral systolic blood pressure	Seated office blood pressure (mmHg)	15 weeks
Secondary	Clinical peripheral diastolic blood pressure	Seated brachial office blood pressure (mmHg)	15 weeks
Secondary	Brachial heart rate-systolic pressure product	heart rate*systolic pressure (units)	15 weeks
Secondary	24-hour mean heart rate	Ambulatory heart rate averaged over 24 hours (bpm)	15 weeks
Secondary	24-hour central systolic pressure	Ambulatory pressure averaged over 24 hours (mmHg)	15 weeks
Secondary	24-hour central diastolic pressure	Ambulatory pressure averaged over 24 hours (mmHg)	15 weeks
Secondary	24-hour peripheral Systolic pressure	Ambulatory pressure averaged over 24 hours (mmHg)	15 weeks
Secondary	24-hour peripheral diastolic pressure	Ambulatory pressure averaged over 24 hours (mmHg)	15 weeks
Secondary	24-hour mean heart rate systolic pressure product	Ambulatory heart rate*systolic pressure averaged over 24 hours	15 weeks
Secondary	Daytime myocardial oxygen consumption	Determined by ambulatory heart rate-central systolic pressure product (hours 6:00-21:59) at the end of each study phase (units)	15 weeks
Secondary	Nighttime myocardial oxygen consumption	Determined by ambulatory heart rate-central systolic pressure product (hours 22:00-05:59) at the end of each study phase (units)	15 weeks
Secondary	Daytime heart rate	Mean ambulatory heart rate (hours 6:00-21:59) (bpm)	15 weeks
Secondary	Nighttime heart rate	Mean ambulatory heart rate (hours 22:00-05:59) (bpm)	15 weeks
Secondary	Daytime central systolic pressure	Mean ambulatory central systolic pressure (hours 6:00-21:59) (mmHg)	15 weeks
Secondary	Nighttime central systolic pressure	Mean ambulatory central systolic pressure (hours 22:00-05:59) (mmHg)	15 weeks
Secondary	Daytime peripheral systolic pressure	Mean ambulatory peripheral systolic pressure (hours 6:00-21:59) (mmHg)	15 weeks
Secondary	Nighttime peripheral systolic pressure	Mean ambulatory peripheral systolic pressure (hours 22:00-05:59) (mmHg)	15 weeks
Secondary	Daytime central diastolic pressure	Mean ambulatory central diastolic pressure (hours 6:00-21:59) (mmHg)	15 weeks
Secondary	Nighttime central diastolic pressure	Mean ambulatory central diastolic pressure (hours 22:00-05:59) (mmHg)	15 weeks
Secondary	Daytime peripheral diastolic pressure	Mean ambulatory peripheral diastolic pressure (hours 6:00-21:59) (mmHg)	15 weeks
Secondary	Nighttime peripheral diastolic pressure	Mean ambulatory peripheral diastolic pressure (hours 22:00-05:59) (mmHg)	15 weeks
Secondary	Daytime heart rate systolic blood pressure product	Mean ambulatory heart rate systolic blood pressure product (hours 6:00-21:59) (units)	15 weeks
Secondary	Nighttime heart rate systolic blood pressure product	Mean ambulatory heart rate systolic blood pressure product (hours 22:00-5:59) (units)	15 weeks