Permanent Atrial FibrillationPhase 3APAF-CRTNCT02137187
Atrioventricular Junction Ablation and Biventricular Pacing for Atrial Fibrillation and Heart Failure
A Phase 3 study testing AV junction ablation, CRT and Optimized drug therapy in people with Permanent Atrial Fibrillation, run by Centro Prevenzione Malattie Cardiovascolari N. e V. Corbella at 1 site in Italy.
Trial summary
There is evidence of superiority of AV junction ablation strategy over pharmacological therapy only for symptoms of atrial fibrillation, but not for heart failure, hospitalization, morbidity and mortality. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Permanent Atrial Fibrillation
- What is being tested?
- AV junction ablation, CRT and Optimized drug therapy
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,830 participants
- Where
- 1 siteItaly
- Study dates
- 15 Oct 2014to 31 Jul 2021
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To be eligible, each patient must be in the following condition:
- Permanent atrial fibrillation (>6 months) which has been considered unsuitable for ablation or failed ablation
- Narrow QRS ≤ 110 ms
- Severely symptomatic (atrial fibrillation-related symptoms), refractory to drug therapy for rate control
- At least one hospitalization related to atrial fibrillation and/or heart failure in the previous year (see definition below)
Who cannot join
- New York Heart Association (NYHA) class IV and systolic blood pressure <80 mmHg despite optimized therapy;
- severe concomitant non-cardiac disease;
- need for surgical intervention;
- myocardial infarction within the previous 3 months;
- previous implanted devices (PM/ICD/CRT)
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Department of Cardiology, Ospedali del Tigullio
Lavagna, 16033
Michele Brignole, MD, 0185329567, mbrignole@asl4.liguria.it
About this study
Official title: A Randomized Controlled Trial of Atrioventricular (AV) Junction Ablation and Biventricular Pacing Versus Optimal Pharmacological Therapy in Patients With Permanent Atrial Fibrillation
There is evidence of superiority of AV junction ablation strategy over pharmacological therapy only for symptoms of atrial fibrillation, but not for heart failure, hospitalization, morbidity and mortality. Hypothesis of trial is that AV junction ablation is superior to pharmacological therapy as regard hospitalization and mortality
Read the detailed description
Prospective randomized, controlled, investigator-initiated trial which consists of two specific consecutive(overlapped) phases:
"Morbidity trial" (APAF-CRT morbidity). Small size (280 pts), follow-up 24 months. Primary endpoint: combined of mortality due to heartfailure, hospitalization for heart failure or atrial fibrillation or worsening heart failure. Predefined subgroup analysis for patients with ejection fraction ≤35% versus >35%
"Mortality trial" (APAF-CRT mortality). Large size (pts included in morbidity trial plus additional ~1500 pts, long-term follow-up (at least 4 years). Primary endpoint: total mortality. Predefined subgroup analysis for patients with ejection fraction ≤35% versus >35%
- Conditions
- Permanent Atrial Fibrillation
- Being tested
- AV junction ablation, CRT, Optimized drug therapy, ICD
- Keywords
- Atrial fibrillation, Heart failure, Catheter ablation, Cardiac resynchronization therapy, Implantable defibrillator
- Medical subject headings
- Atrial Fibrillation, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AV junction ablationProcedure or surgery
Also called AV nodal ablation
AV junction ablation
CRTDevice
Also called Cardiac resynchronization therapy
Implantation of device for pacing and cardiac resynchronization therapy (CRT-P or CRT-D according to guidelines)
Optimized drug therapyDrug
Also called Pharmacological therapy
Optimized drug therapy for heart failure and atrial fibrillation rate control
ICDDevice
Also called Implantable defibrillator
Implantable defibrillator (in control Group or in association with CRT in study Group) according to guidelines
| Study group | Role | What they receive |
|---|---|---|
| Drug therapy | Experimental | Control Arm: optimized drug therapy (plus implantable defibrillator (ICD) according to guidelines) Receives: Drug: Optimized drug therapy; Device: ICD |
| Device: AV junction ablation & CRT | Active comparator | AV junction ablation + CRT (CRT-P or CRT-D according to guidelines) + optimized drug therapy Receives: Procedure: AV junction ablation; Device: CRT; Drug: Optimized drug therapy; Device: ICD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Combined end-point
"Morbidity trial" end-points Primary end-point: a combined of (1) mortality due to heart failure, (2) hospitalization for heart failure or uncontrolled intolerable atrial fibrillation, or (3) worsening heart failure
Measured: Upto 3 years
Secondary outcomes (2)
Major clinical events
"Morbidity trial" end-points Secondary end-points: total mortality, total hospitalizations, hospitalization for heart failure and/or atrial fibrillation and worsening heart failure.
Measured: Up to 3 years
Major clinical events
"Mortality trial" end-points Secondary end-point: cardiovascular mortality and hospitalization for heart failure or uncontrolled intolerable atrial fibrillation
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2014 (estimated)
- Study start15 Oct 2014
- Primary completion15 May 2021 (estimated)
- Study completion31 Jul 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Permanent Atrial FibrillationStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,830 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centro Prevenzione Malattie Cardiovascolari N. e V. Corbella
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Claudio Marsano, MD, Study director, Centro Prevenzione Malattie Cardiovascolari N. e V. Corbella
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02137187
- Sponsor's protocol ID
- CPMCV-01-14
- Acronym
- APAF-CRT
- Status last verified
- Jul 2020
- First submitted
- 3 May 2014
- Last updated
- 20 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Chatterjee NA, Upadhyay GA, Ellenbogen KA, McAlister FA, Choudhry NK, Singh JP. Atrioventricular nodal ablation in atrial fibrillation: a meta-analysis and systematic review. Circ Arrhythm Electrophysiol. 2012 Feb;5(1):68-76. doi: 10.1161/CIRCEP.111.967810. Epub 2011 Dec 20.
PubMed 22187425Brignole M, Botto G, Mont L, Iacopino S, De Marchi G, Oddone D, Luzi M, Tolosana JM, Navazio A, Menozzi C. Cardiac resynchronization therapy in patients undergoing atrioventricular junction ablation for permanent atrial fibrillation: a randomized trial. Eur Heart J. 2011 Oct;32(19):2420-9. doi: 10.1093/eurheartj/ehr162. Epub 2011 May 23.
PubMed 21606084Brignole M, Pentimalli F, Palmisano P, Landolina M, Quartieri F, Occhetta E, Calo L, Mascia G, Mont L, Vernooy K, van Dijk V, Allaart C, Fauchier L, Gasparini M, Parati G, Soranna D, Rienstra M, Van Gelder IC; APAF-CRT Trial Investigators. AV junction ablation and cardiac resynchronization for patients with permanent atrial fibrillation and narrow QRS: the APAF-CRT mortality trial. Eur Heart J. 2021 Dec 7;42(46):4731-4739. doi: 10.1093/eurheartj/ehab569.
PubMed 34453840Brignole M, Pokushalov E, Pentimalli F, Palmisano P, Chieffo E, Occhetta E, Quartieri F, Calo L, Ungar A, Mont L; APAF-CRT Investigators. A randomized controlled trial of atrioventricular junction ablation and cardiac resynchronization therapy in patients with permanent atrial fibrillation and narrow QRS. Eur Heart J. 2018 Dec 1;39(45):3999-4008. doi: 10.1093/eurheartj/ehy555.
PubMed 30165479
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of Atrioventricular (AV) Junction Ablation and Biventricular Pacing Versus Optimal Pharmacological Therapy in Patients With Permanent Atrial Fibrillation
- ClinicalTrials.gov ID
- NCT02137187
- Acronym / sponsor ID
- APAF-CRT / CPMCV-01-14
- Conditions
- Permanent Atrial Fibrillation
- Keywords
- Atrial fibrillation, Heart failure, Catheter ablation, Cardiac resynchronization therapy, Implantable defibrillator
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,830 participants (estimated)
- Lead sponsor
- Centro Prevenzione Malattie Cardiovascolari N. e V. CorbellaUniversity, hospital or other
- Study start
- 15 Oct 2014 (actual)
- Primary completion
- 15 May 2021 (estimated)
- Study completion
- 31 Jul 2021 (estimated)
- First posted
- 13 May 2014 (estimated)
- 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.
There is evidence of superiority of AV junction ablation strategy over pharmacological therapy only for symptoms of atrial fibrillation, but not for heart failure, hospitalization, morbidity and mortality. Hypothesis of trial is that AV junction ablation is superior to pharmacological therapy as regard hospitalization and mortality
Detailed description
Prospective randomized, controlled, investigator-initiated trial which consists of two specific consecutive(overlapped) phases:
"Morbidity trial" (APAF-CRT morbidity). Small size (280 pts), follow-up 24 months. Primary endpoint: combined of mortality due to heartfailure, hospitalization for heart failure or atrial fibrillation or worsening heart failure. Predefined subgroup analysis for patients with ejection fraction ≤35% versus >35%
"Mortality trial" (APAF-CRT mortality). Large size (pts included in morbidity trial plus additional ~1500 pts, long-term follow-up (at least 4 years). Primary endpoint: total mortality. Predefined subgroup analysis for patients with ejection fraction ≤35% versus >35%
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Drug therapy | Experimental | Drug: Optimized drug therapy, Device: ICDControl Arm: optimized drug therapy (plus implantable defibrillator (ICD) according to guidelines) |
| Device: AV junction ablation & CRT | Active comparator | Procedure: AV junction ablation, Device: CRT, Drug: Optimized drug therapy, Device: ICDAV junction ablation + CRT (CRT-P or CRT-D according to guidelines) + optimized drug therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Permanent atrial fibrillation (>6 months) which has been considered unsuitable for ablation or failed ablation
- Narrow QRS ≤ 110 ms
- Severely symptomatic (atrial fibrillation-related symptoms), refractory to drug therapy for rate control
- At least one hospitalization related to atrial fibrillation and/or heart failure in the previous year (see definition below)
Key exclusion criteria (5 listed)
- New York Heart Association (NYHA) class IV and systolic blood pressure <80 mmHg despite optimized therapy;
- severe concomitant non-cardiac disease;
- need for surgical intervention;
- myocardial infarction within the previous 3 months;
- previous implanted devices (PM/ICD/CRT)
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 |
|---|---|---|
| AV junction ablationAlso: AV nodal ablationAV junction ablation | Procedure or surgery | Device: AV junction ablation & CRT |
| CRTAlso: Cardiac resynchronization therapyImplantation of device for pacing and cardiac resynchronization therapy (CRT-P or CRT-D according to guidelines) | Device | Device: AV junction ablation & CRT |
| Optimized drug therapyAlso: Pharmacological therapyOptimized drug therapy for heart failure and atrial fibrillation rate control | Drug | Device: AV junction ablation & CRT, Drug therapy |
| ICDAlso: Implantable defibrillatorImplantable defibrillator (in control Group or in association with CRT in study Group) according to guidelines | Device | Device: AV junction ablation & CRT, Drug therapy |
Primary outcome
Combined end-point
Time frame: Upto 3 years
"Morbidity trial" end-points Primary end-point: a combined of (1) mortality due to heart failure, (2) hospitalization for heart failure or uncontrolled intolerable atrial fibrillation, or (3) worsening heart failure
2 secondary outcomes
Major clinical events
Time frame: Up to 3 years
Major clinical events
Time frame: Up to 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2021.
- Background: PubMed 22187425Chatterjee NA, Upadhyay GA, Ellenbogen KA, McAlister FA, Choudhry NK, Singh JP. Atrioventricular nodal ablation in atrial fibrillation: a meta-analysis and systematic review. Circ Arrhythm Electrophysiol. 2012 Feb;5(1):68-76. doi: 10.1161/CIRCEP.111.967810. Epub 2011 Dec 20.
- Results publication: PubMed 21606084Brignole M, Botto G, Mont L, Iacopino S, De Marchi G, Oddone D, Luzi M, Tolosana JM, Navazio A, Menozzi C. Cardiac resynchronization therapy in patients undergoing atrioventricular junction ablation for permanent atrial fibrillation: a randomized trial. Eur Heart J. 2011 Oct;32(19):2420-9. doi: 10.1093/eurheartj/ehr162. Epub 2011 May 23.
- Derived from this study: PubMed 34453840Brignole M, Pentimalli F, Palmisano P, Landolina M, Quartieri F, Occhetta E, Calo L, Mascia G, Mont L, Vernooy K, van Dijk V, Allaart C, Fauchier L, Gasparini M, Parati G, Soranna D, Rienstra M, Van Gelder IC; APAF-CRT Trial Investigators. AV junction ablation and cardiac resynchronization for patients with permanent atrial fibrillation and narrow QRS: the APAF-CRT mortality trial. Eur Heart J. 2021 Dec 7;42(46):4731-4739. doi: 10.1093/eurheartj/ehab569.
- Derived from this study: PubMed 30165479Brignole M, Pokushalov E, Pentimalli F, Palmisano P, Chieffo E, Occhetta E, Quartieri F, Calo L, Ungar A, Mont L; APAF-CRT Investigators. A randomized controlled trial of atrioventricular junction ablation and cardiac resynchronization therapy in patients with permanent atrial fibrillation and narrow QRS. Eur Heart J. 2018 Dec 1;39(45):3999-4008. doi: 10.1093/eurheartj/ehy555.
- 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.
Claudio Marsano, MD study director
Centro Prevenzione Malattie Cardiovascolari N. e V. Corbella
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AV junction ablation, CRT and Optimized drug therapy in people with Permanent Atrial Fibrillation, run by Centro Prevenzione Malattie Cardiovascolari N. e V. Corbella at 1 site in Italy.
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 5 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 20 Jan 2021. 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 Italy. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Michele Brignole, MD (+39 0185 329567, mbrignole@asl4.liguria.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Combined end-point (time frame: Upto 3 years). 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 NCT02137187, which also lists 4 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 20 Jan 2021.