24 Hour Ambulatory Cardiac Oxygen Consumption

Phase 3

Completed

• Conditions: Hypertension
• Interventions: Drug: Nebivolol; Drug: Nebivolol/valsartan; Drug: Valsartan

• Registration Number: NCT05170061
• Lead Sponsor: State University of New York at Buffalo

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2013-02
• Primary Completion: 2014-09
• Study Completion: 2014-12
• Study First Submitted: 2014-12-22
• Status Verified: 2021-12
• Study First Submitted QC: 2021-12-21
• Last Update Submitted: 2021-12-21
• Study First Posted: 2021-12-27
• Last Update Posted: 2021-12-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Nebivolol	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	Nebivolol/valsartan	Combination of nebivolol/valsartan 20/160 mg daily for 1 week followed by 40/320 mg daily for 3 weeks, followed by 1-week down-titration to 20/160 mg daily
Valsartan	Valsartan	Valsartan, 160 mg daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1-week down-titration to 160 mg daily

Primary Outcome Measures

Name	Time	Method
Standard deviation of 24-hour myocardial oxygen consumption	15 weeks	Standard deviation of ACRPP
24-hour myocardial oxygen consumption	15 weeks	Determined by 24-hour ambulatory heart rate-central systolic pressure product \[ACRPP\] at the end of each study phase (units)

Secondary Outcome Measures

Name	Time	Method
Clinical peripheral systolic blood pressure	15 weeks	Seated office blood pressure (mmHg)
Clinical peripheral diastolic blood pressure	15 weeks	Seated brachial office blood pressure (mmHg)
24-hour peripheral Systolic pressure	15 weeks	Ambulatory pressure averaged over 24 hours (mmHg)
Daytime peripheral systolic pressure	15 weeks	Mean ambulatory peripheral systolic pressure (hours 6:00-21:59) (mmHg)
24-hour mean heart rate	15 weeks	Ambulatory heart rate averaged over 24 hours (bpm)
24-hour central systolic pressure	15 weeks	Ambulatory pressure averaged over 24 hours (mmHg)
Brachial heart rate-systolic pressure product	15 weeks	heart rate\*systolic pressure (units)
Daytime myocardial oxygen consumption	15 weeks	Determined by ambulatory heart rate-central systolic pressure product (hours 6:00-21:59) at the end of each study phase (units)
Nighttime myocardial oxygen consumption	15 weeks	Determined by ambulatory heart rate-central systolic pressure product (hours 22:00-05:59) at the end of each study phase (units)
24-hour central diastolic pressure	15 weeks	Ambulatory pressure averaged over 24 hours (mmHg)
24-hour peripheral diastolic pressure	15 weeks	Ambulatory pressure averaged over 24 hours (mmHg)
Nighttime heart rate	15 weeks	Mean ambulatory heart rate (hours 22:00-05:59) (bpm)
Daytime central systolic pressure	15 weeks	Mean ambulatory central systolic pressure (hours 6:00-21:59) (mmHg)
Daytime central diastolic pressure	15 weeks	Mean ambulatory central diastolic pressure (hours 6:00-21:59) (mmHg)
Nighttime central diastolic pressure	15 weeks	Mean ambulatory central diastolic pressure (hours 22:00-05:59) (mmHg)
Daytime peripheral diastolic pressure	15 weeks	Mean ambulatory peripheral diastolic pressure (hours 6:00-21:59) (mmHg)
Daytime heart rate systolic blood pressure product	15 weeks	Mean ambulatory heart rate systolic blood pressure product (hours 6:00-21:59) (units)
Nighttime heart rate systolic blood pressure product	15 weeks	Mean ambulatory heart rate systolic blood pressure product (hours 22:00-5:59) (units)
24-hour mean heart rate systolic pressure product	15 weeks	Ambulatory heart rate\*systolic pressure averaged over 24 hours
Daytime heart rate	15 weeks	Mean ambulatory heart rate (hours 6:00-21:59) (bpm)
Nighttime central systolic pressure	15 weeks	Mean ambulatory central systolic pressure (hours 22:00-05:59) (mmHg)
Nighttime peripheral systolic pressure	15 weeks	Mean ambulatory peripheral systolic pressure (hours 22:00-05:59) (mmHg)
Nighttime peripheral diastolic pressure	15 weeks	Mean ambulatory peripheral diastolic pressure (hours 22:00-05:59) (mmHg)

Trial Locations

Locations (1)

Erie County Medical Center; 🇺🇸 Buffalo, New York, United States