Genetically Targeted Therapy for the Prevention of Symptomatic Atrial Fibrillation in Patients With Heart Failure (GENETIC-AF)

Phase 1

• Conditions: Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]; Atrial Fibrillation; MedDRA version: 20.0Level: PTClassification code 10003658Term: Atrial fibrillationSystem Organ Class: 10007541 - Cardiac disorders

• Registration Number: EUCTR2016-000302-12-NL
• Lead Sponsor: ARCA biopharma, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-08-16
• Last Update Posted: 12 March 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 620

Inclusion Criteria

Patients must meet all of the following inclusion criteria to be eligible for randomization in this study.
1. Age = 18 years and = 85 years at the Screening Visit.
2. Weight = 40 kg at the Randomization Visit.
3. Possess the ß1389Arg/Arg genotype.
4. History of heart failure with reduced left ventricle ejection fraction (HFREF).
a. LVEF < 0.50 assessed at any time during the previous 12 months of the Screening Visit.
5. At least one symptomatic paroxysmal or persistent AF episode = 180 days of the Screening Visit.
a. Qualifying AF episode may be documented by ECG, Holter, TTM, or implanted device. AF documented by implanted device must be a single episode = 60 minutes in duration. Atrial flutter is not considered a qualifying AF episode.
b. Must have experienced AF symptoms = 180 days of the Screening Visit, but these symptoms may overlap with HF symptoms, i.e. may be arrhythmic” (e.g. palpitations, dizziness) or heart failure” (e.g. breathlessness, fatigability) in nature.
6. Clinically appropriate for ECV if AF/AFL is present at the Week 0 Visit, including:
a. Patients with AF/AFL at randomization determined by the Investigator to require ECV.
b. Patients in SR at randomization determined by the Investigator to require ECV if AF/AFL recurs.
7. Receiving guideline indicated oral anticoagulation therapy at the Randomization Visit, which is considered optimal for stroke prevention in the opinion of the Investigator.
8. Systolic blood pressure > 90 mmHg and < 150 mmHg at the Randomization Visit.
9. Female of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Randomization Visit.
a. Female who is surgically sterile or post-menopausal for at least 12 months is not considered to be of childbearing potential.
10. Female of childbearing potential must agree to use a highly effective contraception for the duration of the trial and for at least 30 days following the last dose of study drug.
a. Female who is surgically sterile or post-menopausal for at least 12 months is not considered to be of childbearing potential.
11. Must agree not to participate in a clinical study involving another investigational drug or device throughout the duration of this study.
12. Must be competent to understand the information given in the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved ICF. Must sign the ICF prior to the initiation of any study procedure and not withdraw consent prior to the Randomization Visit.
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 155
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 465

Exclusion Criteria

1. NYHA Class IV symptoms at the Randomization Visit.
2. Significant fluid overload at the Randomization Visit, in the opinion of the Investigator. Evidence of significant fluid overload may include:
a. Mean jugular venous pressure above the clavicle at 90°.
b. Liver congestion.
c. Moist pulmonary rales post-cough.
d. Peripheral edema beyond 1+ pedal not explained by local factors.
3. Permanent AF at the Screening Visit.
a. Permanent AF is defined as an ongoing AF event 1 year or longer in duration in which there is no intervening evidence of SR.
4. More than two ECV procedures within 6 months of the Randomization Visit or if the most recent ECV within 6 months of the Randomization Visit failed to produce SR.
5. Use of any of the following < 7 days of the randomization Visit:
a. Amiodarone, disopyramide, dofetilide, dronedarone, flecainide, propafenone, sotalol, non-dihydropyridine calcium channel blockers, daily NSAIDS (e.g., ibuprofen, celecoxib), thiazolidinediones, or frequent use of short acting nitroglycerin (e.g., > 6 sublingual tablets/week).
b. Note: Amiodarone and dofetilide can be restarted after the start of follow-up if the patient experiences an AF/AFL event or after failure to convert to SR following ECV (see protocol Section 5.8).
6. The presence of a left ventricular assist device (LVAD) or a condition that is likely to require LVAD placement within 6 months of the Randomization Visit.
7. History of a successful atrioventricular node ablation.
8. History of an AF ablation or AFL ablation within 30 days of the Randomization Visit.
9. History of untreated second degree Mobitz II or third degree heart block.
10. History of untreated symptomatic bradycardia or if symptomatic bradycardia is likely on full dose of study drug in the opinion of the Investigator.
11. Heart rate < 60 beats per minute at the Randomization Visit for patients who were not receiving ß-blocker therapy during the screening period.
12. Heart rate > 180 beats per minute at the Randomization Visit.
13. Contraindication or previous history of intolerance to ß-blocker therapy (e.g., untreated valvular disease) or Toprol-XL (e.g., inability to tolerate at least 25mg QD).
14. Myocardial infarction, unstable angina, acute coronary syndrome, cardiac surgery (including PTCA or stent placement), or evidence of new ischemic changes as assessed by ECG = 90 days of the Randomization Visit.
15. Moderate to severe asthma or other obstructive lung disease requiring chronic use (> 2 days/week) of an inhaled ß2-selective adrenergic agonist < 7 days of the Randomization Visit.
16. History of pulmonary hypertension, defined as a systolic pulmonary arterial pressure = 70 mmHg at rest as assessed by echocardiography or right heart catheterization.
17. Known reversible causes of AF such as alcohol intoxication, pulmonary embolism, hyperthyroidism, acute pericarditis, or hypoxemia.
18. Evidence of an appropriate firing of an ICD device for ventricular tachycardia (VT) or ventricular fibrillation (VF) = 90 days of the Randomization Visit.
a. Exception: does not include anti-tachycardia pacing.
19. Untreated thyroid disease, in the opinion of the Investigator, at the Randomization Visit.
20. Serum potassium < 3.5 mmol/L at the Screening Visit.
a. Lab value will be assessed by the central lab at the Screening Visit and any exclusionary results must be corrected prior to randomization as documented by either the central or local lab.
21. Renal failure

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified