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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-004717-12 | EudraCT Number |
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| Name | Class |
|---|---|
| Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK) | OTHER |
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EXAMINE-CAD-DZHK22 is a prospective, randomized, double-blind, placebo-controlled, crossover trial investigating the efficacy of beta blocker (bisoprolol) and calcium channel blocker (diltiazem) therapy in symptomatic patients with non-obstructed coronary arteries according to coronary physiological testing results.
Patients presenting with recurrent angina but non-obstructed coronary arteries are increasingly recognized and have a high morbidity and symptomatic burden. These patients are often misdiagnosed and discharged without further investigation or treatment. Current European Society of Cardiology (ESC) guidelines for the management of patients with chronic coronary syndromes recommend beta blockers or calcium channel blockers, depending on the presence of abnormal vasodilatation or abnormal vasoconstriction. Scientific evidence to support this recommendation, however, is scarce and no randomized clinical trial of this differential therapy has been performed in these patients. The aim of the EXAMINE-CAD-DZHK22 trial is therefore to compare for the first time the efficacy of beta blocker (bisoprolol) and calcium channel blocker (diltiazem) therapy in reducing angina symptoms in symptomatic patients with non-obstructed coronary arteries according to coronary physiology testing results. This study is the first to investigate whether coronary physiology testing can guide therapeutic management of these patients depending on whether abnormalities of vasodilatation or vasoconstriction are present. The EXAMINE-CAD-DZHK22 trial will thus fill an important knowledge and evidence gap in the treatment of these highly symptomatic patients, and has the potential to pave the way for future large-scale clinical trials in symptomatic patients with non-obstructed coronary arteries.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| bisoprolol first, diltiazem second | Experimental | Crossover Design: bisoprolol first, diltiazem second, placebo third |
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| bisoprolol first, placebo second | Experimental | Crossover Design: bisoprolol first, placebo second, diltiazem third |
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| diltiazem first, bisoprolol second | Experimental | Crossover Design: diltiazem first, bisoprolol second, placebo third |
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| diltiazem first, placebo second | Experimental | Crossover Design: diltiazem first, placebo second, bisoprolol third |
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| placebo first, bisoprolol second | Experimental | Crossover Design: placebo first, bisoprolol second, diltiazem third |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bisoprolol | Drug | beta-adrenergic receptor blocker |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in angina symptom severity as measured by the Seattle Angina Questionnaire (SAQ) summary score from each period specific baseline to the end of this period (week 4) | Assessment of angina symptom severity as measured by the SAQ summary score resulting from the SAQ physical limitation scale, SAQ angina frequency scale, and SAQ quality of life scale. The score ranges from 0 to 100, with the lower the score, the higher the symptom severity and limitations. | from each period specific baseline to the end of this period, i.e. baseline and 4 weeks; 6 weeks and 10 weeks; 12 weeks and 16 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| SAQ angina stability scale | Individual SAQ domain to evaluate the disease-specific health status with quantification of patients' symptoms of angina. The score ranges from 0 to 100, with the lower the score, the higher the symptom severity and limitations. | from each period specific baseline to the end of this period, i.e. baseline and 4 weeks; 6 weeks and 10 weeks; 12 weeks and 16 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Aslihan Erbay, MD | Contact | +49 30 450 513 653 | examine-cad@charite.de |
| Name | Affiliation | Role |
|---|---|---|
| Ulf Landmesser, Prof. Dr. | Charité University, Berlin, Germany | Study Chair |
| Barbara E Stähli, Prof. Dr. | Universitätsspital Zürich | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kerckhoff-Klinik gGmbH | Not yet recruiting | Bad Nauheim | 61231 | Germany |
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Subjects will be randomly assigned to 1 of 6 possible treatment sequences. All treatment sequences will include the consecutive treatment with bisoprolol, diltiazem, and placebo.
| placebo first, diltiazem second | Experimental | Crossover Design: placebo first, diltiazem second, bisoprolol third |
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| Diltiazem | Drug | calcium channel blocker |
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| Placebo | Drug | Placebo |
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| SAQ angina frequency scale | Individual SAQ domain to evaluate the disease-specific health status with quantification of patients' symptoms of angina. The score ranges from 0 to 100, with the lower the score, the higher the symptom severity and limitations. | from each period specific baseline to the end of this period, i.e. baseline and 4 weeks; 6 weeks and 10 weeks; 12 weeks and 16 weeks |
| SAQ treatment satisfaction scale | Individual SAQ domain to evaluate the disease-specific treatment satisfaction. The score ranges from 0 to 100, with the higher the score, the higher the treatment satisfaction. | from each period specific baseline to the end of this period, i.e. baseline and 4 weeks; 6 weeks and 10 weeks; 12 weeks and 16 weeks |
| SAQ physical limitation scale | Individual SAQ domain to evaluate the disease-specific health status with quantification of patients' symptoms of angina and the extent to which their angina affects their functioning. The score ranges from 0 to 100, with the lower the score, the higher the symptom severity and limitations. | from each period specific baseline to the end of this period, i.e. baseline and 4 weeks; 6 weeks and 10 weeks; 12 weeks and 16 weeks |
| SAQ quality of life | Individual SAQ domain to evaluate the disease-specific health status with the extent to which their angina affects their quality of life. The score ranges from 0 to 100, with the higher the score, the higher the quality of life. | from each period specific baseline to the end of this period, i.e. baseline and 4 weeks; 6 weeks and 10 weeks; 12 weeks and 16 weeks |
| Duke Activity Status Index (DASI) | Assessment of functional capacity of patients with cardiovascular disease | from each period specific baseline to the end of this period, i.e. baseline and 4 weeks; 6 weeks and 10 weeks; 12 weeks and 16 weeks |
| Rose dyspnea scale | Assessment of patients' dyspnea level with common activities. Scores range from 0 to 4, where 0 indicates no dyspnea with activity and 4 indicates significant limitations due to dyspnea. | from each period specific baseline to the end of this period, i.e. baseline and 4 weeks; 6 weeks and 10 weeks; 12 weeks and 16 weeks |
| Angina diary (Angina episodes per week) | Assessment of angina frequency | from each period specific baseline to the end of this period, i.e. baseline and 4 weeks; 6 weeks and 10 weeks; 12 weeks and 16 weeks |
| Angina diary (nitroglycerin use per week)) | Assessment of need for nitroglycerine | from each period specific baseline to the end of this period, i.e. baseline and 4 weeks; 6 weeks and 10 weeks; 12 weeks and 16 weeks |
| Quality of Life (Short Form 36 health survey questionnaire) | Evaluation of health-related quality of life | from each period specific baseline to the end of this period, i.e. baseline and 4 weeks; 6 weeks and 10 weeks; 12 weeks and 16 weeks |
| Psychological symptoms as assessed by Patient Health Questionnaire (PHQ-9) | Assessment of symptoms for depression in patients with physical illness or physical complaints | from each period specific baseline to the end of this period, i.e. baseline and 4 weeks; 6 weeks and 10 weeks; 12 weeks and 16 weeks |
| Psychological symptoms as assessed by the Hospital Anxiety Depression Scale (HADS)) | Assessment of symptoms for depression and anxiety in patients with physical illness or physical complaints | from each period specific baseline to the end of this period, i.e. baseline and 4 weeks; 6 weeks and 10 weeks; 12 weeks and 16 weeks |
| Functional capacity as assessed by bicycle exercise testing | Assessment of functional capacity in bicycle exercise testing (i.e. maximum load capacity in watt) | from baseline (visit 1) to the end of each treatment period (4 weeks, 10 weeks, 16 weeks) |
| Herz- und Diabeteszentrum NRW | Not yet recruiting | Bad Oeynhausen | 32545 | Germany |
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| Charité University Medicine Berlin, Campus Benjamin Franklin | Recruiting | Berlin | 12203 | Germany |
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| Universitätsklinikum Erlangen | Not yet recruiting | Erlangen | 91054 | Germany |
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| Universitätsklinikum Frankfurt | Not yet recruiting | Frankfurt | 60590 | Germany |
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| Universitäres Herz- und Gefäßzentrum UKE Hamburg | Not yet recruiting | Hamburg | 20246 | Germany |
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| Universitätsklinikum Heidelberg | Not yet recruiting | Heidelberg | 69120 | Germany |
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| Universitätsklinikum Schleswig-Holstein, Campus Kiel | Not yet recruiting | Kiel | 24105 | Germany |
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| Universitätsklinikum Leipzig | Not yet recruiting | Leipzig | 04103 | Germany |
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| Universitätsmedizin der Johannes Gutenberg-Universität Mainz | Not yet recruiting | Mainz | 55131 | Germany |
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| Universitätsmedizin Mannheim | Not yet recruiting | Mannheim | 68167 | Germany |
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| Deutsches Herzzentrum München des Freistaates Bayern - Klinik an der Technischen Universität München | Not yet recruiting | München | 80636 | Germany |
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| Robert-Bosch-Krankenhaus | Not yet recruiting | Stuttgart | 70376 | Germany |
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| Inselspital, Universitätsspital Bern | Not yet recruiting | Bern | 3010 | Switzerland |
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| Universitäres Herzzentrum Zürich, Universitätsspital Zürich | Not yet recruiting | Zurich | 8091 | Switzerland |
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| ID | Term |
|---|---|
| D017566 | Microvascular Angina |
| D003329 | Coronary Vasospasm |
| D000788 | Angina Pectoris, Variant |
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D000787 | Angina Pectoris |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
| D003327 | Coronary Disease |
| D000789 | Angina, Unstable |
| D002637 | Chest Pain |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
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| ID | Term |
|---|---|
| D017298 | Bisoprolol |
| D000319 | Adrenergic beta-Antagonists |
| D004110 | Diltiazem |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D018674 | Adrenergic Antagonists |
| D018663 | Adrenergic Agents |
| D018377 | Neurotransmitter Agents |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D045505 | Physiological Effects of Drugs |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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