Clinical trial NCT05170061: 24 Hour Ambulatory Cardiac Oxygen Consumption
Official title: Ambulatory 24-Hour Cardiac Oxygen Consumption and Blood Pressure-Heart Rate Variability: Effects of Nebivolol and Valsartan Alone and in Combination
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Keywords: Myocardial oxygen consumption
Systolic blood pressure
Diastolic blood pressure
Variability in hemodynamic indicators
Valsartan
Nebivolol
IEM ambulatory monitoring
Lead sponsor: State University of New York at Buffalo
Sponsor class: OTHER
First posted: 2021-12-27
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Random-order-entry 3-way crossover of active treatments; all participants receive all 3 active treatments with 6 possible experimental sequences (arms)
Primary purpose: TREATMENT

Brief summary: A randomized,double-blind, 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.

Eligibility criteria: 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

Primary outcomes:
measure: ACRPP: 24-hour Ambulatory Central Rate-pressure Product (Also Called TTI, CTTI)
timeFrame: measurement after 4 weeks in each treatment arm
Secondary outcomes:
measure: Cuff SBP
timeFrame: After 4 weeks in each treatment arm
measure: Cuff DBP
timeFrame: After 4 weeks in each treatment arm
measure: Ambulatory Brachial Double Product
timeFrame: After 4 weeks in each treatment arm
measure: Ambulatory Mean Heart Rate
timeFrame: After 4 weeks in each treatment arm
measure: Ambulatory Mean Central Diastolic BP
timeFrame: After 4 weeks in each treatment arm
measure: 24-hour Brachial Systolic BP
timeFrame: 4 weeks
measure: 24-hour Brachial Diastolic BP
timeFrame: After 4 weeks in each treatment arm
measure: Daytime ACRPP (Ambulatory Central Rate-Pressure Product (Also Called TTI, CTTI)
timeFrame: After 4 weeks in each treatment arm
measure: Nighttime ACRPP
timeFrame: After 4 weeks in each treatment arm
measure: Daytime Heart Rate
timeFrame: After 4 weeks in each treatment arm
measure: Nighttime Heart Rate
timeFrame: 4 weeks
measure: Daytime Central Systolic Pressure
timeFrame: After 4 weeks in each treatment arm
measure: Nighttime Central Systolic Pressure
timeFrame: 4 weeks
measure: Daytime Brachial Systolic Pressure
timeFrame: After 4 weeks in each treatment arm
measure: Nighttime Brachial Systolic Pressure
timeFrame: 4 weeks
measure: Daytime Central Diastolic Pressure
timeFrame: 4 weeks
measure: Nighttime Central Diastolic Pressure
timeFrame: After 4 weeks in each treatment arm
measure: Daytime Brachial Diastolic Pressure
timeFrame: 4 weeks
measure: Nighttime Brachial Diastolic Pressure
timeFrame: After 4 weeks in each treatment arm
measure: Ambulatory Daytime Brachial Rate-pressure Product
timeFrame: After 4 weeks in each treatment arm
measure: Ambulatory Nighttime Brachial Rate-pressure Product
timeFrame: After 4 weeks in each treatment arm
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Erie County Medical Center
state: New York
Study officials:
affiliation: SUNY Buffalo
name: Joseph L Izzo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.2015.03.009. Epub 2015 Mar 28.