Cardiac Allograft VasculopathyPhase 4VANISH-CAVNCT03405831
Effect of Ivabradine on Exercise Capacity After Heart Transplantation
A Phase 4 study testing Ivabradine in people with Cardiac Allograft Vasculopathy and Transplanted Heart Complication, run by Finn Gustafsson at 1 site in Denmark.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Cardiac Allograft Vasculopathy, Transplanted Heart Complication
- What is being tested?
- Ivabradine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 1 siteDenmark
- Study dates
- 17 Apr 2018to Dec 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
Department of Cardiology, Copenhagen University Hospital, Rigshospitalet
Copenhagen, DK-2100
Finn Gustafsson, MD PhD DMSc, +45 3545 9743, finng@dadlnet.dk
Lærke Nelson, MD, +45 3545 9549, laerke.marie.nelson@regionh.dk
About this study
Official title: 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.
Read the 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.
- Being tested
- Ivabradine, Placebo
- Keywords
- Heart transplantation, Exercise capacity, Heart rate, Cardiac allograft vasculopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IvabradineDrug
Also called Procoralan
Ivabradine, oral tablets, 5 mg, coated in gelatine capsules to ensure blinding, 1 capsule twice a day, for a period of 12 weeks
PlaceboDrug
Placebo, gelatine capsules to ensure blinding, 1 capsule twice daily, for a period of 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Ivabradine | Active comparator | Study participants in this arm will receive ivabradin 5 mg bid for a period of 12 weeks. Receives: Drug: Ivabradine |
| Placebo | Placebo comparator | Study participants in this arm will receive placebo bid for a period of 12 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
ΔVO2max
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.
Measured: The VO2max is assessed at baseline and 12 weeks follow-up.
Secondary outcomes (16)
ΔHRrest
Change in resting HR (beats/min) from baseline to 12 weeks follow-up
Measured: 12 weeks
ΔHRreserve
Change in HR reserve (beats/min) from baseline to 12 weeks follow-up
Measured: 12 weeks
ΔLVmass
Change in left ventricular (LV) mass (g) evaluated by cardiac MRI from baseline to 12 weeks follow-up
Measured: 12 weeks
ΔLVEF
Change in left ventricular ejection fraction (LVEF) (%) evaluated by cardiac MRI from baseline to 12 weeks follow-up
Measured: 12 weeks
Δmitral deceleration time
Change in mitral decelaration time (ms) evaluated by echocardiography from baseline to 12 weeks follow-up
Measured: 12 weeks
ΔE/é
Change in E/é evaluated by echocardiography from baseline to 12 weeks follow-up
Measured: 12 weeks
ΔE/A ratio
Change in E/A ratio evaluated by echocardiography from baseline to 12 weeks follow-up
Measured: 12 weeks
Δisovolumetric relaxation time
Change in isovolumetric relaxation time (ms) evaluated by echocardiography from baseline to 12 weeks follow-up
Measured: 12 weeks
Δtransmitral flow rate
Change in transmitral flow rate (volume/min) evaluated by cardiac MRI from baseline to 12 weeks follow-up
Measured: 12 weeks
Δpulmonary venous flow
Change in pulmonary venous flow (volume/min) evaluated by cardiac MRI from baseline to 12 weeks follow-up
Measured: 12 weeks
ΔLVEDV
Change in LVEDV (left ventricular end diastolic volume) (ml) evaluated by cardiac MRI from baseline to 12 weeks follow-up
Measured: 12 weeks
ΔLVESV
Change in LVESV (left ventricular end systolic volume) (ml) evaluated by cardiac MRI from baseline to 12 weeks follow-up
Measured: 12 weeks
ΔLV peak filling rate
Change in left ventricular (LV) peak filling rate (volume/min) evaluated by cardiac MRI from baseline to 12 weeks follow-up
Measured: 12 weeks
Δtime to peak filling
Change in time to peak filling (sec) evaluated by cardiac MRI from baseline to 12 weeks follow-up
Measured: 12 weeks
ΔQOL KCCQ
Change in QOL score evaluated by Kansas City Cardiomyopathy Questionnaire from baseline to 12 weeks follow-up
Measured: 12 weeks
ΔQOL EQ-5D-5L
Change in QOL score evaluated by EQ-5D-5L questionnaire from baseline to 12 weeks follow-up
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2018
- Study start17 Apr 2018
- Primary completionDec 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiac Allograft VasculopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a prospective single-center, double-blinded, placebo controlled, randomized study in long-term heart transplant recipients. Patients who meet the eligibility criteria will be randomized 1:1 at inclusion for one of two treatment groups: (i) treatment with ivabradine 5 mg bid or (ii) treatment with placebo bid for a period of 12 weeks. 35 participants will be enrolled.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Finn Gustafsson
- Sponsor type
- University, hospital or other
- Collaborators
- Danish Heart Foundation, Copenhagen University Hospital, Rigshospitalet
- Responsible party
- Sponsor-investigator, Finn Gustafsson, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Lærke Nelson, MD, Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03405831
- Sponsor's protocol ID
- RH-HJE-LN-01
- Acronym
- VANISH-CAV
- Status last verified
- Mar 2019
- First submitted
- 5 Jan 2018
- Last updated
- 5 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Ivabradine Treatment on Exercise Capacity in Patients With Cardiac Allograft Vasculopathy After Heart Transplantation
- ClinicalTrials.gov ID
- NCT03405831
- Acronym / sponsor ID
- VANISH-CAV / RH-HJE-LN-01
- Keywords
- Heart transplantation, Exercise capacity, Heart rate, Cardiac allograft vasculopathy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Finn GustafssonUniversity, hospital or other
- Collaborators
- Danish Heart Foundation, Copenhagen University Hospital, Rigshospitalet
- Study start
- 17 Apr 2018 (actual)
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 23 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a prospective single-center, double-blinded, placebo controlled, randomized study in long-term heart transplant recipients. Patients who meet the eligibility criteria will be randomized 1:1 at inclusion for one of two treatment groups: (i) treatment with ivabradine 5 mg bid or (ii) treatment with placebo bid for a period of 12 weeks. 35 participants will be enrolled.
| Arm | Type | Receives |
|---|---|---|
| Ivabradine | Active comparator | Drug: IvabradineStudy participants in this arm will receive ivabradin 5 mg bid for a period of 12 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboStudy participants in this arm will receive placebo bid for a period of 12 weeks. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients > 1 year post heart transplantation
- CAV verified by coronary angiography or intravascular ultrasound
- Resting HR > 80 bpm
- Age > 18 years
- Signed informed consent
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IvabradineAlso: ProcoralanIvabradine, oral tablets, 5 mg, coated in gelatine capsules to ensure blinding, 1 capsule twice a day, for a period of 12 weeks | Drug | Ivabradine |
| PlaceboPlacebo, gelatine capsules to ensure blinding, 1 capsule twice daily, for a period of 12 weeks | Drug | Placebo |
Primary outcome
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.
16 secondary outcomes
ΔHRrest
Time frame: 12 weeks
ΔHRreserve
Time frame: 12 weeks
ΔLVmass
Time frame: 12 weeks
ΔLVEF
Time frame: 12 weeks
Δmitral deceleration time
Time frame: 12 weeks
ΔE/é
Time frame: 12 weeks
ΔE/A ratio
Time frame: 12 weeks
Δisovolumetric relaxation time
Time frame: 12 weeks
Δtransmitral flow rate
Time frame: 12 weeks
Δpulmonary venous flow
Time frame: 12 weeks
ΔLVEDV
Time frame: 12 weeks
ΔLVESV
Time frame: 12 weeks
ΔLV peak filling rate
Time frame: 12 weeks
Δtime to peak filling
Time frame: 12 weeks
ΔQOL KCCQ
Time frame: 12 weeks
ΔQOL EQ-5D-5L
Time frame: 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lærke Nelson, MD principal investigator
Copenhagen University Hospital, Rigshospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ivabradine in people with Cardiac Allograft Vasculopathy and Transplanted Heart Complication, run by Finn Gustafsson at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Finn Gustafsson, MD PhD DMSc (+45 35459743, finng@dadlnet.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ΔVO2max (time frame: The VO2max is assessed at baseline and 12 weeks follow-up.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2019.