Catecholaminergic Polymorphic Ventricular TachycardiaNCT01117454
Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia
A study testing Flecainide Acetate and Beta blocker in people with Catecholaminergic Polymorphic Ventricular Tachycardia, run by Vanderbilt University Medical Center at 10 sites in United States.
Trial summary
The purpose of this study is to test whether the addition of oral flecainide to standard therapy will reduce ventricular ectopy on exercise test compared to placebo plus standard therapy in patients with Catecholaminergic Polymorphic Ventricular Tachycardia. Read more about this study
- Who is it for?
- Ages 5 to 99 years
- Conditions the study is for
- Catecholaminergic Polymorphic Ventricular Tachycardia
- What is being tested?
- Flecainide Acetate and Beta blocker
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 10 sitesUnited States
- Study dates
- Dec 2011to Dec 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 5 to 99 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Clinical diagnosis of CPVT, based on:
- reproducible polymorphic or bidirectional ventricular tachycardia with exercise OR B. Ventricular ectopy on exercise test with RYR2 or CASQ2 mutation
- Functioning ICD in place
- On stable dose of standard therapy defined as the maximal tolerated dose of beta-blocker and may include a calcium channel blocker
- Patients on flecainide or mexiletine are also eligible for enrollment after a 1 week "washout" period during which flecainide or mexiletine is discontinued, and standard therapy alone is used.
Who cannot join
- Females who are pregnant or plan to be pregnant during the study period
- Children < 5 years of age
- Patients unable to perform treadmill exercise
- Patients with significant structural heart disease
- Patients with features consistent with Andersen-Tawil syndrome A. Periodic paralysis or unexplained weakness B. Dysmorphic facies C. Known KCNJ2 mutation
- Patients with known hypersensitivity to flecainide
- Patients on amiodarone
- Patients not expected to comply with follow-up
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
MetroHealth Medical Center
Cleveland, Ohio, 44109
Nationwide Children's Hospital
Columbus, Ohio, 43205
Duke University
Durham, North Carolina, 27705
Cook Children's Hospital
Fort Worth, Texas, 76104
East Carolina University
Greenville, North Carolina, 27834
University of California Los Angeles
Los Angeles, California, 90095
Vanderbilt University
Nashville, Tennessee, 37027
NYU Langone Medical Center
New York, New York, 10010
Children's Hospital of Orange County
Orange, California, 92868
University of Utah
Salt Lake City, Utah, 84112
About this study
Official title: A Prospective Randomized Crossover Trial of Oral Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia
The purpose of this study is to test whether the addition of oral flecainide to standard therapy will reduce ventricular ectopy on exercise test compared to placebo plus standard therapy in patients with Catecholaminergic Polymorphic Ventricular Tachycardia.
Read the detailed description
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a genetic arrhythmia syndrome characterized by frequent ventricular ectopy and polymorphic, classically bidirectional ventricular tachycardia with physical or emotional stress, which also carries a risk of ventricular fibrillation and sudden death, despite no structural heart abnormality. Treatment consists of beta-blockers and/or calcium channel blockers, but up to 30% of patients require implantable cardioverter-defibrillators (ICDs) due to recurrent symptoms on medical therapy. In an animal model, flecainide was found to directly target the molecular defect in CPVT. In a retrospective clinical study in patients with CPVT we have seen improvement of ventricular ectopy on exercise tests when flecainide is added to standard therapy. We propose a prospective trial of flecainide added to standard therapy in CPVT patients to test the hypothesis that flecainide will reduce ventricular ectopy on exercise testing compared to placebo plus standard therapy.
This will be a single-blind (blinded subjects) randomized cross-over study, in which each patient will receive treatment A (flecainide or placebo) for at least 3 months and, after a 1 week wash-out, treatment B (placebo or flecainide) for at least 3 months.
- Being tested
- Flecainide Acetate, Placebo, Beta blocker
- Keywords
- Catecholaminergic Polymorphic Ventricular Tachycardia, implantable cardioverter-defibrillator, flecainide
- Medical subject headings
- Polymorphic Catecholaminergic Ventricular Tachycardia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Flecainide AcetateDrug
oral flecainide with the dose titrated to achieve a serum level between 0.5-0.8 mcg/ml
PlaceboDrug
placebo, similar in appearance to flecainide
Beta blockerDrug
Standard therapy with beta-blocker (nadolol, atenolol, metoprolol, or propranolol) continues throughout the trial.
| Study group | Role | What they receive |
|---|---|---|
| Flecainide then placebo | Other | In this crossover study, half of the subjects will be randomized to flecainide plus standard therapy with beta-blockers first, then crossover to placebo plus standard therapy with beta-blockers. Receives: Drug: Flecainide Acetate; Drug: Placebo; Drug: Beta blocker |
| Placebo then flecainide | Other | In this crossover study, half of the subjects will be randomized to placebo plus standard therapy with beta-blockers first, then crossover to flecainide plus standard therapy with beta-blockers. Receives: Drug: Flecainide Acetate; Drug: Placebo; Drug: Beta blocker |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Ventricular Ectopy or VT During Exercise Treadmill Testing
Hypothesis: the addition of oral flecainide to standard therapy will reduce ventricular ectopy and/or VT on treadmill exercise treadmill testing in patients with CPVT, compared to placebo plus standard therapy.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2010 (estimated)
- Study startDec 2011
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Catecholaminergic Polymorphic Ventricular TachycardiaStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prince Joseph Kannankeril, Vanderbilt University Medical Center
- Investigators
- Prince J Kannankeril, MD, MSCI, Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01117454
- Sponsor's protocol ID
- 100472
- Status last verified
- May 2017
- First submitted
- 4 May 2010
- Last updated
- 14 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Watanabe H, Chopra N, Laver D, Hwang HS, Davies SS, Roach DE, Duff HJ, Roden DM, Wilde AA, Knollmann BC. Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans. Nat Med. 2009 Apr;15(4):380-3. doi: 10.1038/nm.1942. Epub 2009 Mar 29.
PubMed 19330009van der Werf C, Kannankeril PJ, Sacher F, Krahn AD, Viskin S, Leenhardt A, Shimizu W, Sumitomo N, Fish FA, Bhuiyan ZA, Willems AR, van der Veen MJ, Watanabe H, Laborderie J, Haissaguerre M, Knollmann BC, Wilde AA. Flecainide therapy reduces exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia. J Am Coll Cardiol. 2011 May 31;57(22):2244-54. doi: 10.1016/j.jacc.2011.01.026.
PubMed 21616285Kannankeril PJ, Moore JP, Cerrone M, Priori SG, Kertesz NJ, Ro PS, Batra AS, Kaufman ES, Fairbrother DL, Saarel EV, Etheridge SP, Kanter RJ, Carboni MP, Dzurik MV, Fountain D, Chen H, Ely EW, Roden DM, Knollmann BC. Efficacy of Flecainide in the Treatment of Catecholaminergic Polymorphic Ventricular Tachycardia: A Randomized Clinical Trial. JAMA Cardiol. 2017 Jul 1;2(7):759-766. doi: 10.1001/jamacardio.2017.1320.
PubMed 28492868
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Randomized Crossover Trial of Oral Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia
- ClinicalTrials.gov ID
- NCT01117454
- Acronym / sponsor ID
- 100472
- Keywords
- Catecholaminergic Polymorphic Ventricular Tachycardia, implantable cardioverter-defibrillator, flecainide
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- Dec 2011
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 5 May 2010 (estimated)
- Results
- Posted 17 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test whether the addition of oral flecainide to standard therapy will reduce ventricular ectopy on exercise test compared to placebo plus standard therapy in patients with Catecholaminergic Polymorphic Ventricular Tachycardia.
Detailed description
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a genetic arrhythmia syndrome characterized by frequent ventricular ectopy and polymorphic, classically bidirectional ventricular tachycardia with physical or emotional stress, which also carries a risk of ventricular fibrillation and sudden death, despite no structural heart abnormality. Treatment consists of beta-blockers and/or calcium channel blockers, but up to 30% of patients require implantable cardioverter-defibrillators (ICDs) due to recurrent symptoms on medical therapy. In an animal model, flecainide was found to directly target the molecular defect in CPVT. In a retrospective clinical study in patients with CPVT we have seen improvement of ventricular ectopy on exercise tests when flecainide is added to standard therapy. We propose a prospective trial of flecainide added to standard therapy in CPVT patients to test the hypothesis that flecainide will reduce ventricular ectopy on exercise testing compared to placebo plus standard therapy.
This will be a single-blind (blinded subjects) randomized cross-over study, in which each patient will receive treatment A (flecainide or placebo) for at least 3 months and, after a 1 week wash-out, treatment B (placebo or flecainide) for at least 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Flecainide then placebo | Other | Drug: Flecainide Acetate, Drug: Placebo, Drug: Beta blockerIn this crossover study, half of the subjects will be randomized to flecainide plus standard therapy with beta-blockers first, then crossover to placebo plus standard therapy with beta-blockers. |
| Placebo then flecainide | Other | Drug: Flecainide Acetate, Drug: Placebo, Drug: Beta blockerIn this crossover study, half of the subjects will be randomized to placebo plus standard therapy with beta-blockers first, then crossover to flecainide plus standard therapy with beta-blockers. |
Who may qualify
- Ages
- 5 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Clinical diagnosis of CPVT, based on:
- Functioning ICD in place
- On stable dose of standard therapy defined as the maximal tolerated dose of beta-blocker and may include a calcium channel blocker
- Patients on flecainide or mexiletine are also eligible for enrollment after a 1 week "washout" period during which flecainide or mexiletine is discontinued, and standard therapy alone is used.
Key exclusion criteria (8 listed)
- Females who are pregnant or plan to be pregnant during the study period
- Children < 5 years of age
- Patients unable to perform treadmill exercise
- Patients with significant structural heart disease
- Patients with features consistent with Andersen-Tawil syndrome A. Periodic paralysis or unexplained weakness B. Dysmorphic facies C. Known KCNJ2 mutation
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 |
|---|---|---|
| Flecainide Acetateoral flecainide with the dose titrated to achieve a serum level between 0.5-0.8 mcg/ml | Drug | Flecainide then placebo, Placebo then flecainide |
| Placeboplacebo, similar in appearance to flecainide | Drug | Flecainide then placebo, Placebo then flecainide |
| Beta blockerStandard therapy with beta-blocker (nadolol, atenolol, metoprolol, or propranolol) continues throughout the trial. | Drug | Flecainide then placebo, Placebo then flecainide |
Primary outcome
Number of Patients With Ventricular Ectopy or VT During Exercise Treadmill Testing
Time frame: 3 months
Hypothesis: the addition of oral flecainide to standard therapy will reduce ventricular ectopy and/or VT on treadmill exercise treadmill testing in patients with CPVT, compared to placebo plus standard therapy.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19330009Watanabe H, Chopra N, Laver D, Hwang HS, Davies SS, Roach DE, Duff HJ, Roden DM, Wilde AA, Knollmann BC. Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans. Nat Med. 2009 Apr;15(4):380-3. doi: 10.1038/nm.1942. Epub 2009 Mar 29.
- Background: PubMed 21616285van der Werf C, Kannankeril PJ, Sacher F, Krahn AD, Viskin S, Leenhardt A, Shimizu W, Sumitomo N, Fish FA, Bhuiyan ZA, Willems AR, van der Veen MJ, Watanabe H, Laborderie J, Haissaguerre M, Knollmann BC, Wilde AA. Flecainide therapy reduces exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia. J Am Coll Cardiol. 2011 May 31;57(22):2244-54. doi: 10.1016/j.jacc.2011.01.026.
- Background: PubMed 28492868Kannankeril PJ, Moore JP, Cerrone M, Priori SG, Kertesz NJ, Ro PS, Batra AS, Kaufman ES, Fairbrother DL, Saarel EV, Etheridge SP, Kanter RJ, Carboni MP, Dzurik MV, Fountain D, Chen H, Ely EW, Roden DM, Knollmann BC. Efficacy of Flecainide in the Treatment of Catecholaminergic Polymorphic Ventricular Tachycardia: A Randomized Clinical Trial. JAMA Cardiol. 2017 Jul 1;2(7):759-766. doi: 10.1001/jamacardio.2017.1320.
- 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.
Prince J Kannankeril, MD, MSCI principal investigator
Vanderbilt University
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Flecainide Acetate and Beta blocker in people with Catecholaminergic Polymorphic Ventricular Tachycardia, run by Vanderbilt University Medical Center at 10 sites in United States.
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 5 inclusion and 8 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: finished, as of the sponsor's last update on 14 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With Ventricular Ectopy or VT During Exercise Treadmill Testing (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01117454, which also lists 3 linked publications.
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 14 Jun 2017.