Clinical trial NCT01979614: Study of the Vascular Effects of Serelaxin
Official title: A Multicenter, Double Blind, Randomized, Parallel Group, Placebo-controlled Study to Evaluate the Effects of Intravenous Serelaxin Infusion on Micro- and Macrovascular Function in Patients With Coronary Artery Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronary Artery Disease
Keywords: coronary artery disease
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-11-08
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double blind, randomized, parallel group, placebo controlled study
Primary purpose: TREATMENT

Brief summary: This was a mechanistic study in patients with coronary artery disease on the effects of Serelaxin on micro- and macrovascular function.

Detailed description: double blind, randomized, parallel group, placebo controlled study

Eligibility criteria: Inclusion Criteria:

* Male and female patients ≥18 years of age, with body weight \<160 kg.
* Patients with proven obstructive coronary artery disease, determined either by functional (e.g. treadmill testing) or non-invasive clinical imaging assessments (e.g. stress-echo, PET or SPECT myocardial perfusion), or invasive coronary angiography or by CT coronary angiography at any point in time in patients with or without mild left ventricular systolic dysfunction (LVSD)

Exclusion Criteria:

* Previous treatment with serelaxin (also known as: RLX030, relaxin)
* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study treatment.
* Current or planned dialysis.
* Impaired renal function during screening defined as an estimated glomerular filtration rate (eGFR) at screening and prior to treatment of \<30 mL/min/1.73 m2, calculated using the simplified Modification of Diet in Renal Disease (sMDRD) equation due to potential issue with administration of GdDTPA used as the MRI contrast agent.
* Sick-Sinus-Syndrome
* Current or history of pulmonary edema, including suspected sepsis.
* restrictive, or constrictive cardiomyopathy (does not include restrictive mitral filling patterns seen on Doppler echocardiographic assessments of diastolic function)
* Known significant valvular disease (including any of the following: severe aortic stenosis \[AVA \< 1.0 or peak gradient \> 50 on prior or current echocardiogram\], severe aortic regurgitation, or severe mitral stenosis).
* Clinical diagnosis of acute coronary syndrome (ACS) including unstable angina within 30 days prior to screening as determined by both clinical and enzymatic criteria
* Troponin elevation and dynamics indicative of ACS at any time between screening and randomization.
* Previous myocardial infarction within 3 months of screening
* History of Coronary Artery Bypass Graft (CABG) surgery
* Heart failure due to significant arrhythmias (including any of the following: ventricular tachycardia, bradyarrhythmias with ventricular rate \< 45 beats per minute or any second or third degree AV block or atrial fibrillation/flutter with ventricular response of \> 120 beats per minute)
* Any surgical or medical condition which in the opinion of the investigator may place the patient at higher risk from his/her participation in the study (e.g., history of poor tolerance of adenosine or 3 vessel coronary disease)
* Acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy (does not include restrictive mitral filling patterns seen on Doppler echocardiographic assessments of diastolic function).

Primary outcomes:
measure: Statistical Analysis of Change From Baseline to Day 3 in Myocardial Perfusion Endpoints Compared With Mid Perfusion Reserve Index Using ANCOVA End Points
timeFrame: baseline to Day 3
Secondary outcomes:
measure: Change From Baseline in Aortic Distensibility Measured by MRI
timeFrame: At pre-dose on Day 1 (baseline) until Day 180 after the start of drug infusion
measure: Change From Baseline in Aortic Velocity
timeFrame: At pre-dose on Day 1 (baseline) until Day 180 after the start of drug infusion
measure: Change From Baseline in Augmentation Index Measured From Sphygmocor Device
timeFrame: Day1, Day 2, Day 3, Day 30 and Day 180 after the start of infusion
measure: Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance
timeFrame: Day1, Day 2, Day 3, Day 30 and Day 180 after the start of infusion
measure: Change From Baseline in Pulse Wave Velocity Measured From Carotid-femoral Pulse Wave Analysis
timeFrame: Day1, Day 2, Day 3, Day 30 and Day 180 after the start of infusion
measure: Serum Concentration of Serelaxin
timeFrame: Day1, Day 2, Day 3 and Day 30 after the start of infusion
measure: Serum Concentration of Antibodies to Serelaxin
timeFrame: From pre-dose on Day 1 until Day 30 after the start of drug infusion
measure: Systemic Clearance of Serelaxin
timeFrame: From pre-dose on Day 1 until 48h after the start of drug infusion
Other outcomes:
Locations:
city: Clydebank
country: United Kingdom
facility: Novartis Investigative Site
state: West Dumbartonshire
city: Edinburgh
country: United Kingdom
facility: Novartis Investigative Site
city: Leicester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: