24 Hour Ambulatory Cardiac Oxygen Consumption (ACRPP)

University at Buffalo (UB)

Status and phase: Completed; Phase 3

Conditions: Hypertension

Treatments: Drug: Nebivolol/valsartan combination; Drug: Valsartan; Drug: Nebivolol

Study type: Interventional

Funder types: Other

Identifiers

NCT05170061

BYS-IT-76

Details and patient eligibility

About

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.

Full 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.

Enrollment: 26 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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26 participants in 6 patient groups

Sequence 1: Nebivolol first, then valsartan, then combination of nebivolol/valsartan

Active Comparator group

Description:

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; then 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; then 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

Treatment:

Drug: Nebivolol

Drug: Valsartan

Drug: Nebivolol/valsartan combination

Sequence 2: Nebivolol first, then combination of nebivolol/valsartan; then valsartan

Active Comparator group

Description:

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; then 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; then 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

Treatment:

Drug: Nebivolol

Drug: Valsartan

Drug: Nebivolol/valsartan combination

Sequence 3: Valsartan first, then Nebivolol, then combination of nebivolol/valsartan,

Active Comparator group

Description:

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; then 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; then 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;

Treatment:

Drug: Nebivolol

Drug: Valsartan

Drug: Nebivolol/valsartan combination

Sequence 4: Valsartan first, then combination of nebivolol/valsartan, then Nebivolol,

Active Comparator group

Description:

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; then 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; then 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;

Treatment:

Drug: Nebivolol

Drug: Valsartan

Drug: Nebivolol/valsartan combination

Sequence 5: Combination of nebivolol/valsartan first, then Nebivolol, then Valsartan,

Active Comparator group

Description:

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; then 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; then 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;

Treatment:

Drug: Nebivolol

Drug: Valsartan

Drug: Nebivolol/valsartan combination

Sequence 6: Combination of nebivolol/valsartan first, then Valsartan, then Nebivolol, ,

Active Comparator group

Description:

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; then 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; then 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; then

Treatment:

Drug: Nebivolol

Drug: Valsartan

Drug: Nebivolol/valsartan combination