24 Hour Ambulatory Cardiac Oxygen Consumption

NCT05170061 | Completed Phase 3 Results DMC

• 1 other identifier: BYS-IT-76
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension

Keywords

Myocardial oxygen consumption; Systolic blood pressure; Diastolic blood pressure; Variability in hemodynamic indicators; Valsartan; Nebivolol; IEM ambulatory monitoring

Outcome Measures

Primary Outcomes (1)

• ACRPP: 24-hour Ambulatory Central Rate-pressure Product (Also Called TTI, CTTI)

  ACRPP is the product of estimated aortic mean systolic pressure (mean aortic pressure estimated using a transfer function applied to brachial cuff blood pressure) during the systolic time interval adjusted for heart rate. Units are (mmHg\*beats/min).

  measurement after 4 weeks in each treatment arm

Secondary Outcomes (21)

• Cuff SBP

  After 4 weeks in each treatment arm

• Cuff DBP

  After 4 weeks in each treatment arm

• Ambulatory Brachial Double Product

  After 4 weeks in each treatment arm

• Ambulatory Mean Heart Rate

  After 4 weeks in each treatment arm

• Ambulatory Mean Central Diastolic BP

  After 4 weeks in each treatment arm

Study Arms (6)

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

ACTIVE COMPARATOR

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

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

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

ACTIVE COMPARATOR

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

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

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

ACTIVE COMPARATOR

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;

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

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

ACTIVE COMPARATOR

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;

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

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

ACTIVE COMPARATOR

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;

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

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

ACTIVE COMPARATOR

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

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

Interventions

Nebivolol DRUG

Nebivolol 20 mg daily (1 week) followed by nebivolol 40 mg daily (3 weeks) followed by nebivolol 20 mg daily (1 week)

Also known as: Bystolic

Sequence 1: Nebivolol first, then valsartan, then combination of nebivolol/valsartan; Sequence 2: Nebivolol first, then combination of nebivolol/valsartan; then valsartan; Sequence 3: Valsartan first, then Nebivolol, then combination of nebivolol/valsartan,; Sequence 4: Valsartan first, then combination of nebivolol/valsartan, then Nebivolol,; Sequence 5: Combination of nebivolol/valsartan first, then Nebivolol, then Valsartan,; Sequence 6: Combination of nebivolol/valsartan first, then Valsartan, then Nebivolol, ,

Valsartan DRUG

Valsartan 160 mg daily (1 week) followed by valsartan 320 mg daily (3 weeks) followed by valsartan 160 mg daily (1 week).

Also known as: Diovan

Sequence 1: Nebivolol first, then valsartan, then combination of nebivolol/valsartan; Sequence 2: Nebivolol first, then combination of nebivolol/valsartan; then valsartan; Sequence 3: Valsartan first, then Nebivolol, then combination of nebivolol/valsartan,; Sequence 4: Valsartan first, then combination of nebivolol/valsartan, then Nebivolol,; Sequence 5: Combination of nebivolol/valsartan first, then Nebivolol, then Valsartan,; Sequence 6: Combination of nebivolol/valsartan first, then Valsartan, then Nebivolol, ,

Nebivolol/valsartan combination DRUG

Valsartan/Nebivolol, 160/20 mg daily (1 week) followed by valsartan/nebivolol 320/40 mg daily (3 weeks) followed by valsartan/nebivolol 160/20 mg daily (1 week)

Also known as: Diovan/Bystolic

Sequence 1: Nebivolol first, then valsartan, then combination of nebivolol/valsartan; Sequence 2: Nebivolol first, then combination of nebivolol/valsartan; then valsartan; Sequence 3: Valsartan first, then Nebivolol, then combination of nebivolol/valsartan,; Sequence 4: Valsartan first, then combination of nebivolol/valsartan, then Nebivolol,; Sequence 5: Combination of nebivolol/valsartan first, then Nebivolol, then Valsartan,; Sequence 6: Combination of nebivolol/valsartan first, then Valsartan, then Nebivolol, ,

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• State University of New York at Buffalo: lead

Study Sites (1)

Erie County Medical Center

Buffalo, New York, 14215, United States

Location

Related 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.2015.03.009. Epub 2015 Mar 28.

  PMID: 26116459 RESULT

MeSH Terms

Conditions

Hypertension

Interventions

Nebivolol; Valsartan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tetrazoles; Azoles; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Limitations and Caveats

Relatively small sample size limits extrapolation. Small number of non-blacks precludes racial stratification.

Results Point of Contact

• Title: Joseph Izzo MD
• Organization: SUNYBuffalo

jizzo@buffalo.edu

7168985625

Study Officials

• Joseph L Izzo, MD

  SUNY Buffalo

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blinded: drugs formulated into capsules by an outside research pharmacist who held the codes until study completion
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Random-order-entry 3-way crossover of active treatments; all participants receive all 3 active treatments with 6 possible experimental sequences (arms)

Study Record Dates

• First Submitted: December 22, 2014
• First Posted: December 27, 2021
• Study Start: February 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: December 1, 2014
• Last Updated: June 8, 2025
• Results First Posted: June 8, 2025

Record last verified: 2025-05

Locations

US (1)