Persistent symptoma… · Phase III (2023-505962-28-00)

Start 8 May 2024 · Status Authorised, recruiting · 7 EU/EEA countries · 10 sites · Protocol CryoStopPersAF

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)

Status Authorised, recruiting

Participants planned 226

Countries 7

Sites 10

Persistent symptomatic atrial fibrillation

Key facts

Sponsor: Region Oerebro Laen, Gottsegen National Cardiovascular Center, Národny ustav srdcovych a cievnych chorob a.s., University Of Pecs
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
Trial duration: 8 May 2024 → ongoing
Decision date (initial): 2025-09-29
Transition trial: Yes
Low-intervention: No
Rare-disease indication: No
Vulnerable population: Yes

External identifiers

EU CT number: 2023-505962-28-00
EudraCT number: 2021-006614-37
ClinicalTrials.gov: NCT05939076

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

The main focus is to evaluate the impact of early interventional management of persistent AF.

The primary goal is to evaluate if early pulmonary vein isolation performed with the Arctic Front cryoballoon as first-line therapy is superior to antiarrhythmic drugs (AAD) in preventing atrial arrhythmia recurrences.

We hypothesized that first-line PVI using the cryoballon, at an early stage of the AF disease, will result in a 25 % reduction in any atrial tachyarrhythmia recurrence at 12 months compared to the AAD group.

Secondary objectives 2

The secondary goal is to evaluate the impact of early invasive intervention on health related quality of life (HRQOL) and symptoms, and on safety in comparison to primary AAD therapy, using generic and disease-specific HRQOL questionnaires and also assess Quality Adjusted Life Years (QALYs) score and EHRA classification of symptoms.
The third goal is to assess the impact of an early intervention on cardiovascular health care use (hospitalisations and other health care utilization) and its relation to AF burden and to assess treatment burden and cost-effectiveness compared to AAD.

Conditions and MedDRA coding

Persistent symptomatic atrial fibrillation

Version	Level	Code	Term	System organ class
22.0	LLT	10081865	Cardiac catheter ablation	10042613

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

Non-longstanding persistent symptomatic AF with at least 2 episodes within last 24 months (both shorter than 12 months in duration), the latest episode within the previous 6 months and, one should be documented on a 12 lead ECG or Holter monitor. a) Classical persistent AF as defined by ESC guidelines, b) Persistent AF which has progressed from paroxysmal AF (patients who have been cardioverted within 7 days of onset provided a history of spontaneous conversion of episodes to sinus rhythm is lacking in near time)
Age 18 – 75 years
Candidate for rhythm control therapy; AF ablation or AAD based on symptomatic AF. As an example, BMI >35 would not according to clinical praxis be a candidate for AF ablation and thereby not suitable for participation in the study.

Exclusion criteria 16

Regular daily use of antiarrhythmic drugs of class I or III at adequate therapeutic dosages (pill-in-the-pocket permitted, beta- blockers permitted).
Previous AF ablation or surgery.
Severe heart failure (NYHA III-IV).
Reduced left ventricular ejection fraction (LVEF ≤40 % during sinus rhythm).
Hypertrophic cardiomyopathy (septal or posterior wall thickness >1.5 cm)
Severely enlarged LA with left atrial volume indexed to body surface area (LAVI, ml/m2) > 48.
Significant valvular disease requiring treatment or valve protesis.
Severe COPD stage III or chronic kidney disease (eGFR< 30 umol/l).
Planned cardiac intervention within the next 12 months or cardiac surgery last 6 months.
Myocardial infarction, revascularisation previous 6 months.
Stroke or TIA within previous 6 months.
Tachycardiomyopathy.
Dependent on VVI pacing.
Conventional contraindications for AF ablation including AF due to reversible causes and contraindications for both class IC and class III antiarrhythmic drugs.
Expected survival less than 3 years, alcohol or drug abuse.
Participation in another trial or absence of consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

The primary endpoint is freedom from atrial tachyarrhythmia recurrence lasting ≥ 6 minutes (in the absence of AAD in ablation group) as documented by 12-lead ECG, ECG rhythm strip, Holter, or an ICM, from initiation of treatment excluding the first 3 months (blanking period) to 12 months post after initiation of allocated treatment.

Secondary endpoints 13

Compare the effect of the two first-line treatment strategies with respect to total atrial arrhythmia burden (% time in AF/AT) at 12, 24, and 36 months.
Compare the effect of the two first-line treatment strategies with respect to AF progression and reversion as measured by combination of reduced number of AF progressions or increased number of AF reversions after 3 months blanking. Progression or transition to more severe AF forms such as longstanding persistent or permanent AF and AF regression as going in the opposite direction from persistent to paroxysmal to sinus rhythm at 12, 24 and 36 months.
Compare the effect of the two first-line treatment strategies with respect to healthcare utilization for cardiovascular reasons (number of cardioversions, ablations, AAD initiations, cardiovascular hospitalizations, emergency department visits and unplanned outpatient visits after 3 months blanking) and its relation to AF burden.
Compare the effect of the two first-line treatment strategies with respect to health care costs at 36 months.
Compare the effect of the two first-line treatment strategies with respect to single and multiple procedure success (freedom from ECG documented atrial tachyarrhythmia after the 1st and last ablation procedure respectively) at 12, 24, and 36 months.
Compare the effect of the two first-line treatment strategies with respect to frequency and type of adverse events, recorded continuously and classified whether related to treatment, and whether serious.
Compare the effect of the two first-line treatment strategies with respect to frequency of withdrawals / 'cross-overs' over time.
Compare the effect of the two first-line treatment strategies with respect to Quality of Life measured by SF-36, EQ-5D and AFSS as change from baseline to each of months 12, 24, and 36 months. The rhythm and pulse at the time of the evaluation will be recorded.
Compare the effect of the two first-line treatment strategies with respect to EHRA Symptom Classification, assessed as change from baseline to each of months 12, 24, and 36 months.
Compare the effect of the two first-line treatment strategies with respect to cognitive function as measured by Trail Making Test A and B from baseline to each of months 12, 24, and 36 months. The rhythm and pulse at the time of the evaluation will be recorded.
Compare the effect of the two first-line treatment strategies with respect to blood pressure, systolic and diastolic (mmHg) after 10 minutes rest at baseline compared to each of months 12, 24, and 36 months. The rhythm and pulse at the time of the evaluation will be recorded.
Compare the effect of the two first-line treatment strategies with respect to covariate adjusted primary endpoint (analysis using following covariates at baseline: coronary artery disease, hypertension, LAVI).
Compare the effect of the two first-line treatment strategies with respect to reverse atrial remodeling assessed by P wave variables from ECG (P-wave duration), biomarkers (NT pro-BNP, IL6, D-dimer), and left atrial size and function (LAVI, ejection fraction, atrial strain) by echocardiography, corrected for BSA, at 12, 24 and 36 months.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

—

SCP208166 · ATC

Route of administration: ORAL USE
Max daily dose: 900 mg milligram(s)
Max total dose: 900 mg milligram(s)
Max treatment duration: 36 Month(s)
Authorisation status: Authorised
ATC code: C01BC03 — PROPAFENONE
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

—

SCP15543769 · ATC

Route of administration: ORAL USE
Max daily dose: 200 mg milligram(s)
Max total dose: 200 mg milligram(s)
Max treatment duration: 36 Month(s)
Authorisation status: Authorised
ATC code: C01BC04 — FLECAINIDE
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Dronedarone

SCP175137 · ATC

Active substance: Dronedarone
Route of administration: ORAL USE
Max daily dose: 400 mg milligram(s)
Max total dose: 400 mg milligram(s)
Max treatment duration: 360 Month(s)
Authorisation status: Authorised
ATC code: C01BD07 — DRONEDARONE
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Sotalol

SCP209245 · ATC

Active substance: Sotalol
Route of administration: ORAL USE
Max daily dose: 320 mg milligram(s)
Max total dose: 320 mg milligram(s)
Max treatment duration: 36 Month(s)
Authorisation status: Authorised
ATC code: C07AA07 — SOTALOL
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Oerebro Laen

Sponsor organisation: Region Oerebro Laen
Address: Sodra Grev Rosengatan
City: Orebro
Postcode: 701 85
Country: Sweden

Scientific contact point

Organisation: Region Oerebro Laen
Contact name: Carina Blomström-Lundqvist

Public contact point

Organisation: Region Oerebro Laen
Contact name: Carina Blomström-Lundqvist

Gottsegen National Cardiovascular Center

Sponsor organisation: Gottsegen National Cardiovascular Center
Address: Kerulet, Haller Utca 29/IX., IX. Kerulet Haller Utca 29/IX. IX. Kerulet
City: Budapest
Postcode: 1096
Country: Hungary

Scientific contact point

Organisation: Gottsegen National Cardiovascular Center
Contact name: Csaba Földesi

Public contact point

Organisation: Gottsegen National Cardiovascular Center
Contact name: Csaba Földesi

Národny ustav srdcovych a cievnych chorob a.s.

Sponsor organisation: Národny ustav srdcovych a cievnych chorob a.s.
Address: Pod Krasnou Horkou 1, Nove Mesto Nove Mesto
City: Bratislava
Postcode: 831 01
Country: Slovakia

Scientific contact point

Organisation: Národny ustav srdcovych a cievnych chorob a.s.
Contact name: Martin Svetlošák

Public contact point

Organisation: Národny ustav srdcovych a cievnych chorob a.s.
Contact name: Martin Svetlošák

University Of Pecs

Sponsor organisation: University Of Pecs
Address: Ifjusag Utja 13
City: Pecs
Postcode: 7624
Country: Hungary

Scientific contact point

Organisation: University Of Pecs
Contact name: Peter Kupo

Public contact point

Organisation: University Of Pecs
Contact name: Peter Kupo

Sponsor responsibilities

Article 77 compliance: Region Oerebro Laen
Contact point sponsor: Region Oerebro Laen
Article 77 implementation: Region Oerebro Laen

Locations

7 EU/EEA countries · 10 investigational sites