E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003658 |
E.1.2 | Term | Atrial fibrillation |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this study is to determine whether early RF ablation treatment, using the CARTO® 3 or CARTO ® XP System, and THERMOCOOL ® Catheter Family (including THERMOCOOL® SF or THERMOCOOL® SMARTTOUCH™) in subjects with Paroxysmal AF (PAF), delays progression of AF compared with drug therapy (either rate or rhythm control) using current AF management guidelines. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with recurrent AF for 2 years, with ≥ 2 episodes over the last 6 months; 1 episode within the last 1 year (12 months) must be documented by electrocardiogram (ECG), TTM, HM, or telemetry strip.
• HATCH Score of at least ≥1 and ≤ 4.
• Eligible for catheter ablation and for anti-arrhythmic or rate control medications, after having failed no more than 2 prescribed drugs (either anti-arrhythmic or rate control drug).
• Age 60 years or older.
• LA diameter ≤ 55mm by TTE.
• LV ejection fraction ≥ 50% when in sinus rhythm or LV ejection fraction ≥ 35% when in AF.
• Signed Patient Informed Consent Form.
• Able and willing to comply with protocol requirements, including all baseline and followup testing |
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E.4 | Principal exclusion criteria |
• Patients awaiting cardiac transplantation or other cardiac surgery.
• Acute illness (ongoing) or active systemic infection or sepsis.
• Reversible causes of AF, including thyroid disorders, acute alcohol intoxication, recent major surgical procedures or trauma.
• Recent cardiac events including MI, PCI, or valve or bypass surgery in the preceding 3 months.
• Heart failure decompensation.
• Previous stroke.
• Pulmonary embolism or recent atrial embolism/thrombosis.
• Hypertrophic obstructive cardiomyopathy.
• Class IV angina or Class IV CHF (including past or planned heart transplantation).
• Mandated anti-arrhythmic drug therapy for disease conditions other than AF.
• Heritable arrhythmias or increased risk for torsade de pointes with class I or III Drugs.
• Prior LA catheter ablation with the intention of treating AF; prior surgical interventions for AF such as the MAZE procedure.
• Prior AV nodal ablation.
• Patients presenting contra-indications for the study catheter(s), as indicated in the respective Instructions For Use.
• Contraindication to warfarin, other anticoagulation therapy, or all anti-platelet medications.
• Medical conditions limiting expected survival to < 3 years.
• Concurrent participation in any other clinical study.
• Prior history of non-adherence to prescribed drug regimens. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to persistent AF/AT (excluding isthmus-dependent atrial flutter) at 3 years. Persistent AF/AT is defined as AF/AT lasting longer than 7 consecutive days or requiring termination
by cardioversion after 48 hours. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Effectiveness:
• Rate and time to persistent AF/AT at 1 year and 2 years, rate of persistent AF/AT by number of ablations at 3 years.
• Number of repeat ablations and new AAD drugs per subject throughout 3 years followup.
• Rhythm (% subjects in SR, % subjects with recurrent AF) throughout 3 years follow-up.
• Subject’s pre-existing or new onset/worsened condition(s), that may be associated with AF progression, will be collected at baseline and at each follow up visit throughout the 3-year study period; parameters include subject’s age and gender and the following assessments of non-AF health status: LA size; HATCH Score; blood pressure; NYHA Functional of heart disease; diabetes; lipid profile; renal function and, dementia.
Safety:
• Catheter-related complications (ablation); adverse drug reactions (AAD).
Health Economics (HE) Outcomes:
• Health care utilization (number and length of hospitalizations and unscheduled cardiovascular-related visits).
• Quality of Life (QoL) at 3 months, 6 months, 1 year,2 years and 3 years by EQ-5D and AFEQT Questionnaire and change from baseline. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
secondary end points are evaluated at 3 months, 6 months, 1 year, 2 years and 3 years as described above |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Comparison of two standard of care treatment approach that is recommended by the international Atrial Fibrillation management guidelines |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Radiofrequency Catheter Ablation treatment, CE marked devices used in the approved indications |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
China |
Russian Federation |
Switzerland |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |