Chloroquine for Patients With Symptomatic Persistent Atrial Fibrillation: A Prospective Pilot Study

Atrial Fibrillation Clinical Trial

Official title:

Chloroquine for Patients With Symptomatic Persistent Atrial Fibrillation: A Prospective Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02932007
• Other study ID #: Chloroquine AF
• Status: Recruiting
• Phase: Phase 2
• Start date: March 28, 2017
• Est. completion date: September 2020

Study information

• Verified date: October 2018
• Source: University of South Florida
• Contact: Thanh Tran, MPH
• Phone: 813-844-8544
• Email: thanhtran[@]health.usf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this pilot study is to explore the efficacy of chloroquine in terminating persistent AF and assess its potential role as a pharmacological cardioversion agent for the management of AF.

Description:

This is an open-label, pilot study to explore the efficacy of chloroquine in terminating persistent AF within 2 weeks of drug administration and assess its potential role as a pharmacological cardioversion agent for the management of AF. Subjects will be followed for 2 weeks from the start of drug administration to study drug termination.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: September 2020
• Est. primary completion date: March 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age 18 years and older

2. History of symptomatic persistent AF Persistent AF - defined as continuous AF that is sustained more than 7 days but less than 12 months. Episodes of AF of = 48 hours duration in which a decision is made to terminate with electrical or pharmacological cardioversion prior to 7 days will also be classified as persistent AF

3. AF must be documented at least once either by ECG, event monitoring, loop recorder, telemetry, trans-telephonic monitoring, pacemaker or cardiac defibrillator readouts within 24 months prior to enrollment

4. Currently on anticoagulation therapy as indicated per local guidelines, which is considered optimal for stroke prevention in the opinion of the investigator

5. Implanted dual chamber pacemaker/ICD capable of monitoring atrial arrhythmias or willingness to wear a 2 weeks event monitor if patient does not have a device capable of monitoring atrial arrhythmias

6. Signed informed consent

Exclusion Criteria:

1. Age < 18 years

2. AF felt to be secondary to an obvious reversible cause such as, but not limited to, acute myocardial infarction, pulmonary embolism, recent surgery, pericarditis, alcohol intoxication, hypoxemia, or thyrotoxicosis

3. Structural heart disease including patients with artificial heart valves or valvular AF

4. Obstructive coronary artery disease or history of any myocardial infarction

5. Ejection fraction < 50% within 1 year of consent

6. Severe or moderate to severe aortic stenosis, mitral stenosis, aortic regurgitation, or mitral regurgitation per PI discretion

7. Prolonged QTc of >460 msec on baseline ECG

8. Contraindications to quinolines

9. Known allergy or hypersensitivity to Chloroquine

10. Use of amiodarone 12 months prior to enrollment

11. History of AF ablation within 30 days prior to enrollment

12. Renal impairment (eGFR < 30 mL/min/1.73 m2 or Serum Creatinine > 1.25 mg/dL) for subjects over the age of 65

13. Hepatic disease (ALT/AST 2X the upper normal limit)

14. History of alcohol abuse and/or drug abuse per PI discretion

15. Pre-existing auditory damage

16. History of epilepsy

17. Women of child-bearing potential (those who have had a menstrual period in the previous 12 months) who:

• are pregnant or breast-feeding or plan to become pregnant during study or

• who are not surgically sterile and are not practicing two acceptable methods of birth control, or do not plan to continue practicing two acceptable methods of birth control throughout the study (highly effective methods are listed under section 6.0 Pregnancy)

18. Current participation in another clinical study

19. Serious or active medical or psychiatric condition which, in the opinion of the investigator, may interfere with treatment, assessment, or compliance with the protocol

20. Not able to discontinue medications known to have significant interactions with chloroquine

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• Chloroquine Phosphate
Two tablets of study drug are to be taken on the day of study drug initiation and the next day, followed by one tablet each day for the next 12 days. Study drug to be orally administered and taken with food.

Locations

Country	Name	City	State
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of South Florida

Country where clinical trial is conducted

United States, 

References & Publications (7)

Boriani G, Laroche C, Diemberger I, Fantecchi E, Popescu MI, Rasmussen LH, Dan GA, Kalarus Z, Tavazzi L, Maggioni AP, Lip GY. 'Real-world' management and outcomes of patients with paroxysmal vs. non-paroxysmal atrial fibrillation in Europe: the EURObserva — View Citation

BURRELL ZL Jr, MARTINEZ AC. Chloroquine and hydroxychloroquine in the treatment of cardiac arrhythmias. N Engl J Med. 1958 Apr 17;258(16):798-800. — View Citation

Filgueiras-Rama D, Martins RP, Mironov S, Yamazaki M, Calvo CJ, Ennis SR, Bandaru K, Noujaim SF, Kalifa J, Berenfeld O, Jalife J. Chloroquine terminates stretch-induced atrial fibrillation more effectively than flecainide in the sheep heart. Circ Arrhythm — View Citation

Harris L, Downar E, Shaikh NA, Chen T. Antiarrhythmic potential of chloroquine: new use for an old drug. Can J Cardiol. 1988 Sep;4(6):295-300. — View Citation

Lee YS, Hwang M, Song JS, Li C, Joung B, Sobie EA, Pak HN. The Contribution of Ionic Currents to Rate-Dependent Action Potential Duration and Pattern of Reentry in a Mathematical Model of Human Atrial Fibrillation. PLoS One. 2016 Mar 10;11(3):e0150779. do — View Citation

Nguyen T, Jolly U, Sidhu K, Yee R, Leong-Sit P. Atrial fibrillation management: evaluating rate vs rhythm control. Expert Rev Cardiovasc Ther. 2016 Jun;14(6):713-24. doi: 10.1586/14779072.2016.1164033. Epub 2016 Mar 30. Review. — View Citation

Noujaim SF, Stuckey JA, Ponce-Balbuena D, Ferrer-Villada T, López-Izquierdo A, Pandit S, Calvo CJ, Grzeda KR, Berenfeld O, Chapula JA, Jalife J. Specific residues of the cytoplasmic domains of cardiac inward rectifier potassium channels are effective anti — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with termination of AF		Within 2 weeks of study drug initiation
Secondary	Percentage of AF burden	AF burden reported on pacemaker/ICD interrogation or 2-week Holter reports from baseline and 2 weeks post drug initiation	Within 2 weeks of study drug initiation
Secondary	QT intervals	From baseline, pre-treatment ECG compared to 2 weeks post treatment ECG	Within 2 weeks of study drug initiation
Secondary	Time to AF termination	In days on pacemaker/ICD interrogation or Holter reports obtained at 2 weeks after study drug initiation	Within 2 weeks of study drug initiation
Secondary	Percentages of classifications of rhythms identified	From pacemaker/ICD interrogation or Holter reports obtained at 2 weeks after study drug initiation	Within 2 weeks of study drug initiation
Secondary	PR interval	From baseline, pre-treatment ECG compared to 2 weeks post treatment ECG	Within 2 weeks of study drug initiation
Secondary	QRS duration	From baseline, pre-treatment ECG compared to 2 weeks post treatment ECG	Within 2 weeks of study drug initiation