Back to resultsStudy of the Vascular Effects of Serelaxin
Primary Purpose
Coronary Artery Disease
Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Serelaxin
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Coronary Artery Disease focused on measuring coronary artery disease
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).
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Serelaxin
Placebo
Arm Description
Serelaxin was administered at a dose of 30 μg/kg/24h by intravenous infusion for 48 hours
Placebo was administered by intravenous infusion for 48 hours
Outcomes
Primary Outcome Measures
Statistical Analysis of Change From Baseline to Day 3 in Myocardial Perfusion Endpoints Compared With Mid Perfusion Reserve Index Using ANCOVA End Points
Global MPRI (Myocardial Perfusion Reserve Index) is defined as ratio between mean global myocardial blood flow values at rest and during adenosine stress with Mid Perfusion Reserve Index or Midl PRI (Mid Perfusion Reserve Index) which is defined as ratio between mid myocardial blood flow values at rest and during adenosine stress
Secondary Outcome Measures
Change From Baseline in Aortic Distensibility Measured by MRI
Measurements of arterial stiffness from cardiac MRI - Mean (SD) [n]
Aortic distensibility was assessed by MRI and pulse wave velocity using the SphygmoCor device.
(mmHg-1)
Change From Baseline in Aortic Velocity
Summary table for measurements of arterial velocity from cardiac MRI - Mean (SD) [n]
Aortic distensibility was assessed by MRI and pulse wave velocity using the SphygmoCor device
Change From Baseline in Augmentation Index Measured From Sphygmocor Device
Summary of values and change from baseline in augmentation index by time and treatment
The change from baseline in Augmentation Index was analyzed using a repeated measures analysis of covariance including treatment, time, treatment by time, baseline by time interactions and baseline as fixed factors with an unstructured variance-covariance matrixStatistical analysis of change from baseline in augmentation index using repeated measures Analysis of Covariance
Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance
The change from baseline in Augmentation Index was analyzed using a repeated measures analysis of covariance including treatment, time, treatment by time, baseline by time interactions and baseline as fixed factors with an unstructured variance-covariance matrixStatistical analysis of change from baseline in augmentation index using repeated measures Analysis of Covariance
For analysis of change from baseline, only subjects with results at both baseline and post-baseline could be included
The augmentation index is a ratio calculated from the blood pressure waveform, it is a measure of wave reflection and arterial stiffness. Augmentation index is commonly accepted as a measure of the enhancement (augmentation) of central aortic pressure by a reflected pulse wave
Change From Baseline in Pulse Wave Velocity Measured From Carotid-femoral Pulse Wave Analysis
Pulse wave velocity was assessed by the SphygmoCor device
Serum Concentration of Serelaxin
Summary statistics of serelaxin serum PK concentrations
Blood samples were taken to measure serelaxin concentration
Serum Concentration of Antibodies to Serelaxin
Frequency and percentage of anti-Serelaxin antibodies
Blood samples were taken to measure antibodies to serelaxin concentration at Pre-dose on Day 1, and at Day 30 after the start of the 48h drug infusion
Systemic Clearance of Serelaxin
Systemic clearance was estimated using the rate of serelaxin infusion and the steady state concentration
Full Information
NCT ID
NCT01979614
First Posted
November 4, 2013
Last Updated
April 5, 2019
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01979614
Brief Title
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
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
February 3, 2014 (Actual)
Primary Completion Date
August 17, 2016 (Actual)
Study Completion Date
August 17, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease
Keywords
coronary artery disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
double blind, randomized, parallel group, placebo controlled study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
58 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Serelaxin
Arm Type
Experimental
Arm Description
Serelaxin was administered at a dose of 30 μg/kg/24h by intravenous infusion for 48 hours
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo was administered by intravenous infusion for 48 hours
Intervention Type
Drug
Intervention Name(s)
Serelaxin
Other Intervention Name(s)
RLX030, relaxin
Intervention Description
Serelaxin solution diluted in 5% glucose volume/volume (v/v) solution
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
5% v/v glucose solution
Primary Outcome Measure Information:
Title
Statistical Analysis of Change From Baseline to Day 3 in Myocardial Perfusion Endpoints Compared With Mid Perfusion Reserve Index Using ANCOVA End Points
Description
Global MPRI (Myocardial Perfusion Reserve Index) is defined as ratio between mean global myocardial blood flow values at rest and during adenosine stress with Mid Perfusion Reserve Index or Midl PRI (Mid Perfusion Reserve Index) which is defined as ratio between mid myocardial blood flow values at rest and during adenosine stress
Time Frame
baseline to Day 3
Secondary Outcome Measure Information:
Title
Change From Baseline in Aortic Distensibility Measured by MRI
Description
Measurements of arterial stiffness from cardiac MRI - Mean (SD) [n]
Aortic distensibility was assessed by MRI and pulse wave velocity using the SphygmoCor device.
(mmHg-1)
Time Frame
At pre-dose on Day 1 (baseline) until Day 180 after the start of drug infusion
Title
Change From Baseline in Aortic Velocity
Description
Summary table for measurements of arterial velocity from cardiac MRI - Mean (SD) [n]
Aortic distensibility was assessed by MRI and pulse wave velocity using the SphygmoCor device
Time Frame
At pre-dose on Day 1 (baseline) until Day 180 after the start of drug infusion
Title
Change From Baseline in Augmentation Index Measured From Sphygmocor Device
Description
Summary of values and change from baseline in augmentation index by time and treatment
The change from baseline in Augmentation Index was analyzed using a repeated measures analysis of covariance including treatment, time, treatment by time, baseline by time interactions and baseline as fixed factors with an unstructured variance-covariance matrixStatistical analysis of change from baseline in augmentation index using repeated measures Analysis of Covariance
Time Frame
Day1, Day 2, Day 3, Day 30 and Day 180 after the start of infusion
Title
Statistical Analysis of Change From Baseline in Augmentation Index Using Repeated Measures Analysis of Covariance
Description
The change from baseline in Augmentation Index was analyzed using a repeated measures analysis of covariance including treatment, time, treatment by time, baseline by time interactions and baseline as fixed factors with an unstructured variance-covariance matrixStatistical analysis of change from baseline in augmentation index using repeated measures Analysis of Covariance
For analysis of change from baseline, only subjects with results at both baseline and post-baseline could be included
The augmentation index is a ratio calculated from the blood pressure waveform, it is a measure of wave reflection and arterial stiffness. Augmentation index is commonly accepted as a measure of the enhancement (augmentation) of central aortic pressure by a reflected pulse wave
Time Frame
Day1, Day 2, Day 3, Day 30 and Day 180 after the start of infusion
Title
Change From Baseline in Pulse Wave Velocity Measured From Carotid-femoral Pulse Wave Analysis
Description
Pulse wave velocity was assessed by the SphygmoCor device
Time Frame
Day1, Day 2, Day 3, Day 30 and Day 180 after the start of infusion
Title
Serum Concentration of Serelaxin
Description
Summary statistics of serelaxin serum PK concentrations
Blood samples were taken to measure serelaxin concentration
Time Frame
Day1, Day 2, Day 3 and Day 30 after the start of infusion
Title
Serum Concentration of Antibodies to Serelaxin
Description
Frequency and percentage of anti-Serelaxin antibodies
Blood samples were taken to measure antibodies to serelaxin concentration at Pre-dose on Day 1, and at Day 30 after the start of the 48h drug infusion
Time Frame
From pre-dose on Day 1 until Day 30 after the start of drug infusion
Title
Systemic Clearance of Serelaxin
Description
Systemic clearance was estimated using the rate of serelaxin infusion and the steady state concentration
Time Frame
From pre-dose on Day 1 until 48h after the start of drug infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Clydebank
State/Province
West Dumbartonshire
ZIP/Postal Code
G81 4HX
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Edinburgh
ZIP/Postal Code
EHN 2XU
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Leicester
ZIP/Postal Code
LE3 9QP
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Learn more about this trial
Study of the Vascular Effects of Serelaxin
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