The Effect of Nebivolol in Hypertensive Patients With Coronary Arterial Spasm

NCT03930433 | Completed Phase 4 DMC

• 1 other identifier: NevibololSpasm
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

The correlation between endothelial dysfunction and the risk of coronary heart disease is well known through previous studies. The degradation of the function of nitric oxide acting on the endothelium of blood vessels is mainly explained by reduction of synthesis, loss due to oxidative stress, and decreased sensitivity to vascular dilatation action. In particular, patients with high blood pressure have been known to have impaired vascular endothelial function through animal experiments and several clinical studies, mainly due to increased biomechanical friction in the blood vessels and decreased biological availability of nitric oxide, which in turn causes incongruity in the production of nitric monoxide and changes in normal vascular dilatation. There have also been reports recently that early diagnosis and treatment may improve endothelial dysfunction and prevent the progression of coronary artery disease. However, the reality is that the drugs available in vasospastic angina patients with endothelial dysfunction are very limited. Until recently, beta-blockers were reported to inhibit vascular dilatation of adrenaline stimuli, a drug corresponding to relative contraindications in vasospastic angina patients, with one study reporting that propranolol cannot, but rather exacerbates, vasospastic angina. However, a series of reports on the vascular dilatation of the recently developed third-generation beta-blockers have reinvented the role of beta-blockers in vasospastic angina, especially nebivolol (selective, continuous beta-blockers) is known to act on β-1 adrenaline receptor blockings and endothelium to create vascular dilatation, and also to stimulate β-3 adrenaline receptors to cause nitric oxide generation and antioxidant effects in the endothelium of blood vessels. Therefore, this clinical trial seeks to find whether nebivolol will inhibit vascular contraction in hypertensive patients and will work in angiospastic angina patients.

Conditions

Coronary Vasospasm

Keywords

Nebivolol

Outcome Measures

Primary Outcomes (1)

• Changes in coronary spasm

  The descriptive statistics (mean subject number, standard deviation, median value, minimum value, and maximum value) of changes in the baseline and 12-week outcomes will be presented for each treatment group, and the comparison between the three groups for ANOVA or ANOVA Kruskal-Wallis test. Changes in each group will be analyzed using Paired t-test or Wilcoxon signed rank test. An ANCOVA analysis will be performed when there are more influencing factors.

  Baseline to 12 weeks

Secondary Outcomes (3)

• Changes in Quality of Life

  Baseline to 12 weeks

• Changes in mean sitting systolic blood pressure and mean sitting diastolic blood pressure

  Baseline to 6, 12 weeks

• Percentage of target blood pressure reached

  Baseline to 6, 12 weeks

Study Arms (3)

Nebivolol group

ACTIVE COMPARATOR

Oral Nebivolol 5mg / day (2 weeks) -\> 10mg / day (10 weeks)

Drug: Nebivolol

Diltiazem group

PLACEBO COMPARATOR

Oral Diltiazem 90mg / day (2 weeks) -\> 180mg / day (10 weeks)

Drug: Diltiazem

Nebivolol+Diltiazem group

PLACEBO COMPARATOR

Oral Nebivolol 2.5mg / day + Oral Diltiazem 45mg / day (2 weeks) -\> Oral Nebivolol 5mg / day + Oral Diltiazem 90mg / day (10 weeks)

Drug: Nebivolol+Diltiazem

Interventions

Nebivolol DRUG

Patients are randomly assigned to a ratio of 1: 1: 1, divided into 3 groups.

Nebivolol group

Diltiazem DRUG

Patients are randomly assigned to a ratio of 1: 1: 1, divided into 3 groups.

Diltiazem group

Nebivolol+Diltiazem DRUG

Patients are randomly assigned to a ratio of 1: 1: 1, divided into 3 groups.

Nebivolol+Diltiazem group

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• hypertension (stage I-2: Systolic blood pressure 140-179mmHg and diastolic blood pressure 90-109mmHg)
• to 80 years old
• diagnosed with vasospastic angina through coronary angiography and provocation test
• available to outpatient treatment
• voluntarily signed a written consent to participate in the clinical trial

You may not qualify if:

• Previous history of hypersensitivity to beta blockers or calcium channel blockers
• History of dementia or accompanying psychiatric illness or history of drug abuse
• Those who participated in other clinical trials within 1 month before screening
• A person who is unable to perform compliance with the plan and procedures, or who has been judged by the tester to be in a medical condition inappropriate for participation
• Study subjects who are taking drugs that can affect the study drug efficacy evaluation (ACE inhibitors, angiotensin blockers, beta blockers other than clinical trial drugs, calcium antagonists other than clinical trial drugs, diuretics other than indapamide). These subjects are allowed to participate after a wash-out period of at least 2 weeks
• Malignant hypertension (with retinal hemorrhage or papilledema) or known moderate or severe retinopathy (retinal hemorrhage within the last 6 months, visual disturbance, retinal microaneurysm)
• A history of secondary hypertension and all suspected secondary hypertension: coarctation of the aorta, hyperaldosteronism, renal artery stenosis, Cushing's disease, chromatin-positive cell tumor, polycystic kidney disease, etc.
• Patients with orthostatic hypotension with symptoms
• Patients with severe heart disease (heart failure New York Heart Association class 3 and 4), recent 6-month ischemic heart disease (angina pectoris, myocardial infarction), percutaneous coronary intervention, or coronary artery bypass surgery)
• Patients with severe cerebrovascular disease (stroke, cerebral infarction, cerebral hemorrhage within the last 6 months)
• Patients with anuria or severe renal failure (creatinine clearance \<30 mL / min)
• Severe liver failure or AST or ALT\> 3 times the upper limit of normal, biliary obstruction, biliary cirrhosis, cholestasis
• Gastrointestinal diseases and surgery patients that may affect the absorption, distribution, metabolism, and excretion of drugs, current active gastritis and gastrointestinal / rectal bleeding that the tester considers clinically significant, active inflammatory bowel syndrome within the last 12 months
• Pregnant and lactating women, those who have a pregnancy plan during the trial and do not agree with the appropriate method of contraception

Sponsors & Collaborators

• Korea University Anam Hospital: lead
• Korea University Guro Hospital: collaborator
• Korea University Ansan Hospital: collaborator
• Severance Hospital: collaborator

Study Sites (1)

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

MeSH Terms

Conditions

Coronary Vasospasm

Interventions

Nebivolol; Diltiazem

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular 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; Benzazepines

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Group 1: Nebivolol group Group 2: Diltiazem group Group 2: Nebivolol + Diltiazem group

Study Record Dates

• First Submitted: April 24, 2019
• First Posted: April 29, 2019
• Study Start: January 1, 2018
• Primary Completion: March 31, 2019
• Study Completion: March 31, 2019
• Last Updated: March 10, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)