Coronary VasospasmPhase 4NCT03930433
The Effect of Nebivolol in Hypertensive Patients With Coronary Arterial Spasm
A Phase 4 study testing Nebivolol, Diltiazem and Nebivolol+Diltiazem in people with Coronary Vasospasm, run by Korea University Anam Hospital at 1 site in South Korea.
Trial 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… Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Coronary Vasospasm
- What is being tested?
- Nebivolol, Diltiazem and Nebivolol+Diltiazem
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 51 participants
- Where
- 1 siteSouth Korea
- Study dates
- 1 Jan 2018to 31 Mar 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
- Being tested
- Nebivolol, Diltiazem, Nebivolol+Diltiazem
- Keywords
- Nebivolol
- Medical subject headings
- Coronary Vasospasm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NebivololDrug
Patients are randomly assigned to a ratio of 1: 1: 1, divided into 3 groups.
DiltiazemDrug
Patients are randomly assigned to a ratio of 1: 1: 1, divided into 3 groups.
Nebivolol+DiltiazemDrug
Patients are randomly assigned to a ratio of 1: 1: 1, divided into 3 groups.
| Study group | Role | What they receive |
|---|---|---|
| Nebivolol group | Active comparator | Oral Nebivolol 5mg / day (2 weeks) -> 10mg / day (10 weeks) Receives: Drug: Nebivolol |
| Diltiazem group | Placebo comparator | Oral Diltiazem 90mg / day (2 weeks) -> 180mg / day (10 weeks) Receives: 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) Receives: Drug: Nebivolol+Diltiazem |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to 12 weeks
Secondary outcomes (3)
Changes in Quality of Life
Changes in Quality of Life based on Seattle Angina Questionnaire
Measured: Baseline to 12 weeks
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
Measured: Baseline to 6, 12 weeks
Percentage of target blood pressure reached
Percentage of target blood pressure reached from baseline to 6, 12 weeks
Measured: Baseline to 6, 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2019
- Study start1 Jan 2018
- Primary completion31 Mar 2019
- Study completion31 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary VasospasmStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Group 1: Nebivolol group Group 2: Diltiazem group Group 2: Nebivolol + Diltiazem group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Korea University Anam Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Korea University Guro Hospital, Korea University Ansan Hospital, Severance Hospital
- Responsible party
- Principal investigator, Soon Jun Hong, Korea University Anam Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03930433
- Sponsor's protocol ID
- NevibololSpasm
- Status last verified
- Mar 2020
- First submitted
- 24 Apr 2019
- Last updated
- 10 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Nebivolol in Hypertensive Patients With Coronary Arterial Spasm
- ClinicalTrials.gov ID
- NCT03930433
- Acronym / sponsor ID
- NevibololSpasm
- Conditions
- Coronary Vasospasm
- Keywords
- Nebivolol
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Korea University Anam HospitalUniversity, hospital or other
- Collaborators
- Korea University Guro Hospital, Korea University Ansan Hospital, Severance Hospital
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 31 Mar 2019 (actual)
- Study completion
- 31 Mar 2019 (actual)
- First posted
- 29 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- Group 1: Nebivolol group Group 2: Diltiazem group Group 2: Nebivolol + Diltiazem group
| Arm | Type | Receives |
|---|---|---|
| Nebivolol group | Active comparator | Drug: NebivololOral Nebivolol 5mg / day (2 weeks) -> 10mg / day (10 weeks) |
| Diltiazem group | Placebo comparator | Drug: DiltiazemOral Diltiazem 90mg / day (2 weeks) -> 180mg / day (10 weeks) |
| Nebivolol+Diltiazem group | Placebo comparator | Drug: Nebivolol+DiltiazemOral Nebivolol 2.5mg / day + Oral Diltiazem 45mg / day (2 weeks) -> Oral Nebivolol 5mg / day + Oral Diltiazem 90mg / day (10 weeks) |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NebivololPatients are randomly assigned to a ratio of 1: 1: 1, divided into 3 groups. | Drug | Nebivolol group |
| DiltiazemPatients are randomly assigned to a ratio of 1: 1: 1, divided into 3 groups. | Drug | Diltiazem group |
| Nebivolol+DiltiazemPatients are randomly assigned to a ratio of 1: 1: 1, divided into 3 groups. | Drug | Nebivolol+Diltiazem group |
Primary outcome
Changes in coronary spasm
Time frame: Baseline to 12 weeks
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.
3 secondary outcomes
Changes in Quality of Life
Time frame: Baseline to 12 weeks
Changes in mean sitting systolic blood pressure and mean sitting diastolic blood pressure
Time frame: Baseline to 6, 12 weeks
Percentage of target blood pressure reached
Time frame: Baseline to 6, 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nebivolol, Diltiazem and Nebivolol+Diltiazem in people with Coronary Vasospasm, run by Korea University Anam Hospital at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in coronary spasm (time frame: Baseline to 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2020.