INhalation of flecainide to convert recent onset SympTomatic Atrial fibrillation to siNus rhyThm.
- Conditions
- Acute conversion to sinus rhythm (SR) in subjects with recent onset of symptomatic paroxysmal atrial fibrillation (AF).MedDRA version: 20.0Level: LLTClassification code 10034039Term: Paroxysmal atrial fibrillationSystem Organ Class: 100000004849Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2018-000094-76-BE
- Lead Sponsor
- InCarda Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 150
1) Subjects with recent-onset symptomatic AF at presentation.
2) With a duration at onset of symptoms from 1 hour to 48 hours
3) And from one of the following categories:
a) First detected episode of paroxysmal AF
b) Recurrent episode of paroxysmal AF
c) Episode post-cardiac ablation for paroxysmal AF
4)Part C Patient-Led Under Medical Supervision Cardioversion Study only: Subjects whose AF converted to SR with inhaled flecainide and without difficulties or issues with inhalation (in the opinion of the investigator), serious AE(s), or serious AESI(s) in Part A, Part B, or the Part C Medically-Led Cardioversion Study
NOTE: Subjects who:
- are prescribed a pill-in-the-pocket regimen (flecainide or propafenone) for paroxysmal AF, or
- are within 3 months of having undergone ablation of paroxysmal AF, or
- have experienced an episode of new AF but are not currently experiencing an episode of recent-onset paroxysmal AF, or
- are known to have paroxysmal AF (or previously diagnosed with paroxysmal AF) and have one or more previous symptomatic episodes but are not currently experiencing an episode of recent-onset paroxysmal AF may consent to pre-study screening prior to presenting with recentonset
symptomatic AF. These subjects will be eligible to receive study drug only when presenting with symptomatic paroxysmal AF of recentonset
(i.e., = 48 hours), consenting to the full study, and after meeting all eligibility criteria.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50
1) Subject < 18 or > 85 years of age
2) Hemodynamic and/or cardiac instability, with systolic blood pressure < 100 mmHg or > 150 mmHg, and/or ventricular heart rate < 80 bpm or
> 160 bpm.
3) Current AF episode treated with Class I or Class III antiarrhythmic drugs or electrical cardioversion. Subjects whose current AF episode has
been treated with flecainide are eligible if their total cumulative exposure to flecainide does not exceed 320 mg within a 24-hour period,
per site standard of care.
4) History of acute decompensated heart failure (HF)
5)Evidence of significant HF defined as any of the following:
a)Hospitalization in the last 12 months for HF or suspected HF event
b)Most recent assessment of left ventricular ejection fraction (LVEF) < 45%
ii)For subjects in the EU who are participating in the optional HHE Sub-Study, the subject must undergo an HHE during screening to confirm eligibility.
c)New York Heart Association (NYHA) Class II-IV symptoms
d)Medication history suggestive of HF per the Investigator's discretion
6) Evidence of current ongoing MI, such as signs, symptoms , and/or being medicated with anti-anginal medication. In addition, subjects with signs of prior MI who are also asking taking concomitant medications for AP should be evaluated for presence of ongoing ischemia
7) History of myocardial infarction (MI) within 3 months of screening
8) Known uncorrected severe aortic or mitral valve stenosis
9) Hypertrophic cardiomyopathy with outflow tract obstruction
10) Current diagnosis of persistent AF
11) One or more episodes of atrial flutter within 6 months prior to screening or atrial flutter at presentation, except subjects who received ablation for atrial flutter at least 3 months prior to screening and had no subsequent recurrence of atrial flutter prior to enrollment
12) History of any of the following heart abnormalities:
a) Long QT syndrome
b) Conduction disease (e.g. second- or third-degree heart block, bundle branch block)
c) Diagnosed with sinus node dysfunction (e.g., sick sinus syndrome) and/or one of the following:
(i) history of unexplained or cardiovascular syncope,
(ii) known bradycardia suggestive of sinus node dysfunction, and/or
(iii) prior electrical or pharmacological cardioversion associated with prolonged sinus or ventricular pause and/or slow
ventricular rhythm at time of conversion
Note: Sinus node dysfunction in AF is more prevalent in subjects >75 years old.2
d) Brugada Syndrome
e) Torsades de pointes (TdP)
13) Any of the following ECG-related features:
a) QTc interval > 480 msec at screening
b) QRS duration = 120 ms or history of previous documented wide QRS tachycardia
c) Predominantly (i.e., > 30 %) paced heart rhythm
d) Ventricular tachycardia , or excessive premature ventricular complexes ,
prior to dosing as per site telemetry. Site telemetry should be equipped with an alarm system for VT and PVCs or be continuously visually
observed prior to dosing
14) Severe renal impairment (eGFR < 30 mL/min/1.73 m2) or on dialysis
15)Known medical history of abnormal liver function prior to enrollment
16) Uncorrected hypokalemia (defined as serum potassium < 3.6 mEq/L) at screening.
17) Subjects with established pulmonary disease in need of inhalation medication. Subjects with COPD are excluded. Subjects with mild to
moderate asthma that are not experiencing active symptoms at screening and whose asthma is well controlled with steroids and/or asneeded
administration of a bronchodilator are eli
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method