Study cz-020420181253
Study Name
Sequential Hybrid Ablation versus Surgical CryoMaze Alone for the Treatment of Atrial Fibrillation (SurHyb Trial): a multicentre randomized controlled trial
Clinical Trial Registry Identifier
cz-020420181253
Study First Received
02.04.2018 12:53
Sponsor
Agentura pro zdravotnický výzkum České republiky (projekt číslo Nu: NV19-02-00046)
Principal Investigator
Prof. Alan Bulava, MD, PhD, Coinvestigators: Ales Mokracek (Cardiac Centre, Ceske Budejovice, Czech Republic) Pavel Osmancik, Petr Kacer (University Hospital Kralovske Vinohrady, Prague, Czech Republic) Dan Wichterle, Josef Kautzner, Petr Budera (Institute for Clinical and Experimental Medicine, Prague, Czech Republic) Petr Santavy, Tomas Skala (University Hospital Olomouc, Czech Republic) Jiri Ondrasek (Center for Cardiovascular and Transplant Surgery, Brno, Czech Republic)
Information provided by
Prof. Alan Bulava, MD, PhD
Purpose
The main purpose of this prospective, randomized, multicenter, open-label study is to compare the surgical CryoMaze alone with the staged hybrid surgical CryoMaze followed by radiofrequency catheter ablation (RFCA) in patients with non-paroxysmal atrial fibrillation (AF). The main study hypothesis is that routinely performed RFCA, which maximizes completeness of the previous CryoMaze lesion set, will be associated with better sinus rhythm control and favourable clinical outcomes.
Primary endpoints
(1) Time to the first recurrence of AF/AT lasting >6 minutes during the post-blanking follow-up period starting 3 months after the index procedure or failure to discontinue Class I or III antiarrhythmic drugs (AADs) at the beginning of the post-blanking period. Death from any cause will be considered the competing event.
(2) The composite of two competing events: cardiovascular death or hospitalization for any of the following events: arrhythmia recurrence, worsening of heart failure, cardioembolic event, or significant bleeding, as the clinical study endpoint.
Secondary endpoints
(1) The first recurrence of on-AADs AF/AT lasting >6 minutes during the post-blanking follow-up period (i.e., disregarding all off-AAD episodes).
(2) Arrhythmia burden irrespective of AADs (i) within the first year following the index procedure and (ii) throughout the entire duration of the study.
(3) Number of hospitalizations and/or emergency out-patient visits related to AF/AT recurrence, worsening of heart failure or to other cardiovascular diseases.
(4) Number of electrical cardioversions.
(5) Proportion of patients on AADs at the end of follow-up.
(6) RFCA-related complications.
Other endpoints
(1) Description of predilection sites of electrical reconnections (gaps) of surgical circumferential or linear lesions.
(2) Comparison of efficacy (continuity) of endocardial vs. epicardial surgical cryolesions.
(3) Comparison of efficacy (continuity) of argon-based vs. nitrous-oxide-based cryolesions.
(4) Change in LA dimensions and left ventricular function between baseline and the 12-month visit.
(5) Change in N-terminal of the pro-brain natriuretic peptide levels between baseline and the 12-month visit.
(6) Change in quality of life between baseline and the 12-month visit.
Eligibility
Patients scheduled to cardiac surgery because of ischemic or valvular heart disease will be screened in five major cardiovascular or cardiosurgical centres in the Czech Republic: • Cardiac Centre, Ceske Budejovice, • Teaching Hospital Kralovske Vinohrady, Prague, • Institute for Clinical and Experimental Medicine, Prague, • Teaching Hospital Olomouc and • Center for Cardiovascular and Transplant Surgery, Brno
Patients with documented non-paroxysmal AF will (DOI: 10.1093/europace/eux274) be recruited during the clinical review before the surgery. Their demographic data (i.e. age, gender, type of planned surgery) will be recorded in the screening section of the CRF. The reason for non-eligibility will be directly specified in inclusion/exclusion CRF section. Written informed consent with the study will be obtained from all eligible patients prior to the surgery. All participating centres will have an appointed local investigator who will be responsible for appropriate enrolment of patients, their follow up, and data management. The regulations regarding medical confidentiality and data protection will be fulfilled.
Inclusion criteria
Patients with non-paroxysmal AF need to meet all criteria as follows:
• planned cardiac surgery (CABG or valve surgery, or a combination of both) with concomitant CryoMaze as a treatment for non-paroxysmal AF based on the 2018 definition (Calkins et al., 2018),
• documented AF using 12 lead ECG or continuous long-term monitoring devices
• age ?18 years,
• ability to comply mentally/physically with all pre-, post-operative, and follow-up testing and requirements,
• willingness to sign the informed consent form.
Exclusion criteria were as follows:
• paroxysmal AF,
• previous surgical or catheter ablation for AF or atrial tachycardia (AT),
• AF secondary to a reversible or non-cardiac cause,
• left atrial (LA) diameter (in parasternal long axis view) >55 mm,
• chronic kidney disease (CKD Stage ?4),
• estimated life expectancy <1 year,
• pregnancy or the possibility of pregnancy, or breastfeeding potential,
• contraindication to systemic anticoagulation,
• enrolment in a clinical study evaluating another device or drug.
Statistical methods
The primary hypothesis was that the hybrid approach will be superior than surgical ablation only. In our previous non-randomized study on concomitant CryoMaze complemented by an electrophysiological study and RFCA, we found the AF/AT recurrence rate to be 14% after 1 year, based on 7 consecutive days of ECG Holter monitoring (DOI: 10.1111/pace.12686). Before catheter ablation (2-3 months after the CryoMaze procedure), any AT/AF (paroxysmal or persistent) was documented in 54% of patients. Therefore, using the more rigorous ICM-based follow-up, we hypothesized that the actual arrhythmia recurrence rate might be as high as 30% in the hybrid arm (worst-case scenario) and is very likely to be at least 50% in the surgical arm (the optimistic scenario). Hence, for statistical power analysis, we set the off-AAD arrhythmia recurrence rate (primary endpoint) after the hybrid vs. surgical ablation procedure to be 30% vs. 50%, respectively. To ensure 90% power of the study to detect the difference between both arms at the 5% significance level (one-sided Z-test), a total of 101 patients had to be analysed in each arm of the trial. Considering a dropout rate of 10%, the trial was designed with an enrolment target of 222 patients.
Outcome measures will be compared between the randomized groups according to the principle of “intention-to-treat”, additionally, per protocol analysis will be also performed. Cause-specific cumulative incidence functions as a function of follow-up time for the primary (AF/AT recurrence) as well as for the composite clinical endpoint in the presence of competing risk (all-cause death, or non-cardiovascular death, as appropriate) will be shown for the two trial groups. Additionally, hazard ratios (HR) with associated 95% confidence intervals and Wald tests of the treatment group effect, all derived from the Fine-Gray subdistribution hazard model will be calculated. Further, a multivariable Fine-Gray model will be fitted for each outcome measure while including the treatment group among the covariates and adjusting for the effect of gender, age, surgery type, and LA size. Interactions between treatment allocations and those additional patient baseline characteristics will be assessed. P-values <0.05 will be considered statistically significant. Analyses will be performed using the R software.
Contacts and Locations
Contact: Prof. Alan Bulava, MD, PhD, Ceske Budejovice Hospital, Czech Republic, tel. +420 387 87 4389, email: alanbulava@seznam.cz
More Information
Target sample size: 250 Countries of recruitment: Czech Republic
Keywords
Key words: atrial fibrillation, catheter ablation, surgical ablation, CryoMaze, randomized controlled clinical trial, hybrid approach
Status
Enrolment completed
Protocol of the study published
Data being analyzed
Journal of APPLIED BIOMEDICINE: Journal of Applied Biomedicine- (jcu.cz)
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