Clinical trial NCT03255512: Vericiguat Drug-drug Interaction Study With Isosorbite Mononitrate in Stable Coronary Artery Disease Patients
Official title: Multi-center, Randomized, Placebo-controlled, Double-blind Group Comparison Study to Investigate Safety, Tolerability and Blood Pressure of 2.5 mg, 5.0 mg and 10 mg Vericiguat Each Given Over 14 ± 3 Days Together With Isosorbite Mononitrate (ISMN) 60 mg Extended Release Formulation After a Pretreatment Phase (ISMN-starting Dose: 30 mg) in Stable Coronary Artery Disease (CAD) Patients With or Without Heart Failure Aged 30 to 80 Years - Vericiguat ISOsoRbite Mononitrate Interaction (VISOR) Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Coronary Artery Disease
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2017-08-21
Enrollment: 41
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is intended to investigate the pharmacodynamic drug-drug interaction as well as the safety and tolerability of isosorbite mononitrate and vericiguat in patients with stable coronary artery disease.


Eligibility criteria: Inclusion Criteria:

Patients with stable CAD defined by

* coronary artery stenosis in any of the 3 main coronary vessels \> 50% documented by coronary angiography within last 36 months
* or history of myocardial infarction
* Age: 30 to 80 years (inclusive) at the first screening examination
* Body mass index (BMI): above/equal 18.0 and below/equal 36.0 kg / m²

Exclusion Criteria:

* Intervention e.g. revascularization by percutaneous coronary intervention (PCI) and/or coronary artery bypass graft (CABG) during the last 3 months
* Progressive angina with symptoms of worsening of angina within the \< 3 months prior to the first screening examination
* History of recent (\< 6 months prior to the first screening examination) myocardial infarction or unstable angina
* Symptomatic carotid stenosis, or transient ischemic attack or stroke within 3 months prior to the first screening examination or patients with stroke at more than 3 months prior to the first screening examination with significant residual neurologic involvement
* Insulin dependent diabetes mellitus
* Clinically relevant cardiac ischemia at screening
* Clinical significant persistent ischemia, which should be ruled out by clinical judgment of the investigator, based on medical history, available clinical data e.g. past angiograms or preexisting or current exercise testing with any imaging technique (e.g. dobutamine stress echocardiography, adenosine or dobutamine stress cardiac magnetic resonance imaging (CMR), scinthigraphy or exercise ECG)
* Atrial fibrillation, pacemaker, defibrillator, atrial ventricular (AV)-block II and III
* Systolic blood pressure below 110 or above 160 mmHg at first screening visit
* Diastolic blood pressure above 100 mmHg at first screening visit
* Heart rate below 50 or above 100 beats / min (taken from ECG measurement) at first screening visit
* Estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m\*2 at first screening visit

Primary outcomes:
measure: Blood pressure
timeFrame: Up to 8 weeks
measure: Heart rate
timeFrame: Up to 8 weeks
Secondary outcomes:
measure: Number of participants with adverse events
timeFrame: Up to 9 weeks
Other outcomes:
Locations:
city: Bad Krozingen
country: Germany
facility: Universitätsherzzentrum Freiburg - Bad Krozingen
state: Baden-Württemberg
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
state: Baden-Württemberg
city: Bonn
country: Germany
facility: Medizinische Einrichtungen der Universität Bonn
state: Nordrhein-Westfalen
city: Erfurt
country: Germany
facility: SocraTec R&D GmbH
state: Thüringen
city: Berlin
country: Germany
facility: Charité - Campus Virchow-Klinikum (CVK)
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf (UKE)
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Boettcher M, Mikus G, Trenk D, Dungen HD, Donath F, Werner N, Karakas M, Besche N, Schulz-Burck D, Gerrits M, Hung J, Becker C. Vericiguat in combination with isosorbide mononitrate in patients with chronic coronary syndromes: The randomized, phase Ib, VISOR study. Clin Transl Sci. 2022 May;15(5):1204-1214. doi: 10.1111/cts.13238. Epub 2022 Mar 17.