Effect of Ivabradine on Exercise Capacity After Heart Transplantation (VANISH-CAV)

March 4, 2019 updated by: Finn Gustafsson

The Effect of Ivabradine Treatment on Exercise Capacity in Patients With Cardiac Allograft Vasculopathy After Heart Transplantation

This study evaluates whether treatment with ivabradine compared to placebo can improve exercise capacity in long-term heart transplant recipients with cardiac allograft vasculopathy and elevated heart rate at rest.

Patients will receive treatment with either ivabradin or placebo for a period of 12 weeks.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Elevated resting heart rate (HR) is a normal finding after successful heart transplantation (HTx) due to parasympathetic denervation at the operation.

Elevated resting HR is generally acknowledged as a negative predictor of outcome in heart disease. The impact in heart transplant recipients is not fully understood, however, it has been associated with increased risk of developing cardiac allograft vasculopathy (CAV) or death.

Cardiac allograft vasculopathy is a diffuse vascular disease affecting the entire coronary tree. It is the leading cause of death in patients more than 5 years after HTx and it is well known that patients with CAV have markedly reduced exercise capacity.

The association between elevated HR and CAV raises the question whether an intervention to specifically lower HR could improve symptoms and prognosis in heart transplant recipients with CAV and elevated resting HR.

Small studies have shown that HR reduction using the If channel blocker ivabradine after HTx is safe. However, none of these studies were randomized or blinded, and as such proof of any efficacy (beyond HR reduction) after HTx is non-existing. Clearly, there is a need to determine if such treatment could improve exercise capacity, graft function and prognosis after HTx.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
35

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Finn Gustafsson, MD PhD DMSc
  • Phone Number: +45 35459743
  • Email: finng@dadlnet.dk

Study Contact Backup

Study Locations

  • Denmark
      • Copenhagen, Denmark, DK-2100
        • Recruiting
        • Department of Cardiology, Copenhagen University Hospital, Rigshospitalet
        • Contact:
          • Finn Gustafsson, MD PhD DMSc
          • Phone Number: +45 3545 9743
          • Email: finng@dadlnet.dk
        • Contact:
        • Principal Investigator:
          • Lærke Nelson, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 96 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients > 1 year post heart transplantation
  • CAV verified by coronary angiography or intravascular ultrasound
  • Resting HR > 80 bpm
  • Age > 18 years
  • Signed informed consent

Women, who have not yet entered menopause (defined as no menstrual bleeding in the last 12 months), will be required to provide a negative urine human chorionic gonadotropin (hCG) before entering the study and must use a safe birth control method in the total study period.

Exclusion Criteria:

  • Rejection (>H1R) < 3 months
  • Severe renal failure (estimated glomerular filtration rate (GFR) < 30 mL/min/1.73 m2)
  • Inability or contraindication to perform a VO2 max test
  • Presence of any condition that might per se influence exercise performance
  • Known contraindication for treatment with ivabradine
  • Hypersensitivity to the active substance or to any of the excipients of either study drug

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Ivabradine
Study participants in this arm will receive ivabradin 5 mg bid for a period of 12 weeks.
Drug: Ivabradine
Ivabradine, oral tablets, 5 mg, coated in gelatine capsules to ensure blinding, 1 capsule twice a day, for a period of 12 weeks
Other Names:
  • Procoralan
Placebo Comparator: Placebo
Study participants in this arm will receive placebo bid for a period of 12 weeks.
Drug: Placebo
Placebo, gelatine capsules to ensure blinding, 1 capsule twice daily, for a period of 12 weeks

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
ΔVO2max
Time Frame: The VO2max is assessed at baseline and 12 weeks follow-up.
The change in VO2max (ΔVO2max) (mL/kg/min) from baseline to 12 weeks follow-up. The peak oxygen uptake (VO2max) reflects the maximal ability of a person to take in, transport and use oxygen, and it defines the functional aerobic capacity. It is used to provide an overall assessment of exercise capacity.
The VO2max is assessed at baseline and 12 weeks follow-up.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
ΔHRrest
Time Frame: 12 weeks
Change in resting HR (beats/min) from baseline to 12 weeks follow-up
12 weeks
ΔHRreserve
Time Frame: 12 weeks
Change in HR reserve (beats/min) from baseline to 12 weeks follow-up
12 weeks
ΔLVmass
Time Frame: 12 weeks
Change in left ventricular (LV) mass (g) evaluated by cardiac MRI from baseline to 12 weeks follow-up
12 weeks
ΔLVEF
Time Frame: 12 weeks
Change in left ventricular ejection fraction (LVEF) (%) evaluated by cardiac MRI from baseline to 12 weeks follow-up
12 weeks
Δmitral deceleration time
Time Frame: 12 weeks
Change in mitral decelaration time (ms) evaluated by echocardiography from baseline to 12 weeks follow-up
12 weeks
ΔE/é
Time Frame: 12 weeks
Change in E/é evaluated by echocardiography from baseline to 12 weeks follow-up
12 weeks
ΔE/A ratio
Time Frame: 12 weeks
Change in E/A ratio evaluated by echocardiography from baseline to 12 weeks follow-up
12 weeks
Δisovolumetric relaxation time
Time Frame: 12 weeks
Change in isovolumetric relaxation time (ms) evaluated by echocardiography from baseline to 12 weeks follow-up
12 weeks
Δtransmitral flow rate
Time Frame: 12 weeks
Change in transmitral flow rate (volume/min) evaluated by cardiac MRI from baseline to 12 weeks follow-up
12 weeks
Δpulmonary venous flow
Time Frame: 12 weeks
Change in pulmonary venous flow (volume/min) evaluated by cardiac MRI from baseline to 12 weeks follow-up
12 weeks
ΔLVEDV
Time Frame: 12 weeks
Change in LVEDV (left ventricular end diastolic volume) (ml) evaluated by cardiac MRI from baseline to 12 weeks follow-up
12 weeks
ΔLVESV
Time Frame: 12 weeks
Change in LVESV (left ventricular end systolic volume) (ml) evaluated by cardiac MRI from baseline to 12 weeks follow-up
12 weeks
ΔLV peak filling rate
Time Frame: 12 weeks
Change in left ventricular (LV) peak filling rate (volume/min) evaluated by cardiac MRI from baseline to 12 weeks follow-up
12 weeks
Δtime to peak filling
Time Frame: 12 weeks
Change in time to peak filling (sec) evaluated by cardiac MRI from baseline to 12 weeks follow-up
12 weeks
ΔQOL KCCQ
Time Frame: 12 weeks
Change in QOL score evaluated by Kansas City Cardiomyopathy Questionnaire from baseline to 12 weeks follow-up
12 weeks
ΔQOL EQ-5D-5L
Time Frame: 12 weeks
Change in QOL score evaluated by EQ-5D-5L questionnaire from baseline to 12 weeks follow-up
12 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Coronary vessel characterization
Time Frame: Substudy objective is only evaluated at baseline
Substudy objective: To characterize coronary vessels in CAV using new imaging modalities and relating them to functional parameters of cardiac function. Modalities performed at baseline: Intravascular ultrasound (IVUS)/Near-infrared spectroscopy (NIRS), optical coherence tomography (OCT), 82-Rubudium positron emission tomography (PET) scan
Substudy objective is only evaluated at baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Finn Gustafsson

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Rigshospitalet, Denmark
Danish Heart Foundation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Lærke Nelson, MD, Rigshospitalet, Denmark

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 17, 2018

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2019

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 5, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 12, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 23, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 5, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 4, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RH-HJE-LN-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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