The Effect of Nebivolol in Hypertensive Patients With Coronary Arterial Spasm
Primary Purpose
Coronary Vasospasm
Status
Completed
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Nebivolol
Diltiazem
Nebivolol+Diltiazem
Sponsored by
About this trial
This is an interventional treatment trial for Coronary Vasospasm focused on measuring Nebivolol
Eligibility Criteria
Inclusion Criteria:
- hypertension (stage I-2: Systolic blood pressure 140-179mmHg and diastolic blood pressure 90-109mmHg)
- 20 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
Exclusion Criteria:
- 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
Sites / Locations
- Korea University Anam Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Placebo Comparator
Placebo Comparator
Arm Label
Nebivolol group
Diltiazem group
Nebivolol+Diltiazem group
Arm Description
Oral Nebivolol 5mg / day (2 weeks) -> 10mg / day (10 weeks)
Oral Diltiazem 90mg / day (2 weeks) -> 180mg / day (10 weeks)
Oral Nebivolol 2.5mg / day + Oral Diltiazem 45mg / day (2 weeks) -> Oral Nebivolol 5mg / day + Oral Diltiazem 90mg / day (10 weeks)
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Changes in Quality of Life
Changes in Quality of Life based on Seattle Angina Questionnaire
Changes in mean sitting systolic blood pressure and mean sitting diastolic blood pressure
Changes in mean sitting systolic blood pressure and mean sitting diastolic blood pressure
Percentage of target blood pressure reached
Percentage of target blood pressure reached from baseline to 6, 12 weeks
Full Information
NCT ID
NCT03930433
First Posted
April 24, 2019
Last Updated
March 8, 2020
Sponsor
Korea University Anam Hospital
Collaborators
Korea University Guro Hospital, Korea University Ansan Hospital, Severance Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03930433
Brief Title
The Effect of Nebivolol in Hypertensive Patients With Coronary Arterial Spasm
Official Title
The Effect of Nebivolol in Hypertensive Patients With Coronary Arterial Spasm
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
January 1, 2018 (Actual)
Primary Completion Date
March 31, 2019 (Actual)
Study Completion Date
March 31, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Korea University Anam Hospital
Collaborators
Korea University Guro Hospital, Korea University Ansan Hospital, Severance Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Vasospasm
Keywords
Nebivolol
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Group 1: Nebivolol group Group 2: Diltiazem group Group 2: Nebivolol + Diltiazem group
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
51 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Nebivolol group
Arm Type
Active Comparator
Arm Description
Oral Nebivolol 5mg / day (2 weeks) -> 10mg / day (10 weeks)
Arm Title
Diltiazem group
Arm Type
Placebo Comparator
Arm Description
Oral Diltiazem 90mg / day (2 weeks) -> 180mg / day (10 weeks)
Arm Title
Nebivolol+Diltiazem group
Arm Type
Placebo Comparator
Arm Description
Oral Nebivolol 2.5mg / day + Oral Diltiazem 45mg / day (2 weeks) -> Oral Nebivolol 5mg / day + Oral Diltiazem 90mg / day (10 weeks)
Intervention Type
Drug
Intervention Name(s)
Nebivolol
Intervention Description
Patients are randomly assigned to a ratio of 1: 1: 1, divided into 3 groups.
Intervention Type
Drug
Intervention Name(s)
Diltiazem
Intervention Description
Patients are randomly assigned to a ratio of 1: 1: 1, divided into 3 groups.
Intervention Type
Drug
Intervention Name(s)
Nebivolol+Diltiazem
Intervention Description
Patients are randomly assigned to a ratio of 1: 1: 1, divided into 3 groups.
Primary Outcome Measure Information:
Title
Changes in coronary spasm
Description
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.
Time Frame
Baseline to 12 weeks
Secondary Outcome Measure Information:
Title
Changes in Quality of Life
Description
Changes in Quality of Life based on Seattle Angina Questionnaire
Time Frame
Baseline to 12 weeks
Title
Changes in mean sitting systolic blood pressure and mean sitting diastolic blood pressure
Description
Changes in mean sitting systolic blood pressure and mean sitting diastolic blood pressure
Time Frame
Baseline to 6, 12 weeks
Title
Percentage of target blood pressure reached
Description
Percentage of target blood pressure reached from baseline to 6, 12 weeks
Time Frame
Baseline to 6, 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
hypertension (stage I-2: Systolic blood pressure 140-179mmHg and diastolic blood pressure 90-109mmHg)
20 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
Exclusion Criteria:
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
Facility Information:
Facility Name
Korea University Anam Hospital
City
Seoul
ZIP/Postal Code
02841
Country
Korea, Republic of
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
The Effect of Nebivolol in Hypertensive Patients With Coronary Arterial Spasm
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