Rhythm Evaluation for AntiCoagulaTion With COntinuous Monitoring

Atrial Fibrillation Clinical Trial

— REACT COM  

Official title:

Rhythm Evaluation for AntiCoagulaTion With COntinuous Monitoring

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01706146
• Other study ID #: STU00064217
• Secondary ID: 1R34HL113404-017
• Status: Completed
• Phase: Phase 4
• First received: October 10, 2012
• Last updated: January 25, 2016
• Start date: October 2012
• Est. completion date: February 2015

Study information

• Verified date: January 2016
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Data and Safety Monitoring Board
• Study type: Interventional

Clinical Trial Summary

Atrial fibrillation (AF) is the most common sustained abnormal rhythm of the heart, affects an estimated 2.5 to 5 million individuals in the US, and can lead to stroke, heart failure, and premature death. For those with AF and other stroke risk factors, chronic anticoagulation is recommended to prevent intracardiac thrombus formation and stroke even if the AF is infrequent or short-lived. This standard of care is based partly on our inability to rapidly recognize and respond to AF recurrences which can often be brief and asymptomatic, but exposes the patient to the risk of anticoagulant-induced hemorrhage even during prolonged periods of sinus rhythm where the risk of stroke is presumably low.

Recent advances in device technology and drug therapy, however, have the potential to change the way the investigators manage AF. The use of a small leadless subcutaneous implantable cardiac monitor with remote data transmission capabilities (Reveal XT, Medtronic Inc.) provides the ability to remotely and continuously evaluate a patient for AF recurrences, even episodes that are brief and asymptomatic. In addition, release of unique oral thrombin inhibitor approved for use in non-valvular AF(Dabigatran [Pradaxa], Rivaroxaban [Xarelto]) allows for rapid onset anticoagulation within minutes to hours of a single oral dose. Together, these advances allow for continuous AF monitoring with targeted anticoagulation only around the time of an AF episode, thereby reducing the risk of drug-induced hemorrhage while still protecting against stroke.

The aim of this pilot study is to assess the feasibility of intermittent anticoagulation with a rapid-onset oral thrombin inhibitor guided by a continuous AF-sensing implantable cardiac monitor (Reveal XT) with remote data transmission capabilities.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Patients must meet all of the following criteria:

1. Age 18 and above.

2. Patients with non-valvular, non-continuous AF and either:

(A) Infrequent AF episodes without a rhythm control strategy who have had no documented AF lasting > 1 hour for 3 consecutive months (the last 2 of which are on a previously implanted Reveal XT implantable cardiac monitor), or (B) Previous or current rhythm control strategy. Rhythm control strategies may include: i. Class I or Class III antiarrhythmic drugs ii. Pulmonary vein isolation iii. Post-MAZE/minimally invasive MAZE

3. Current Reveal XT implant prior to study enrollment.

4. Documented clinical history of symptomatic or asymptomatic paroxysmal, long-standing persistent or persistent AF prior to rhythm control initiation. The duration of AF must have been > 30 seconds as documented by an external monitor, present 12 lead ECG, or Reveal XT.

5. CHADS2 score of 1 or 2

6. Candidates for chronic anticoagulation with an FDA-approved non-Coumadin oral anticoagulant (dabigatran, rivaroxaban, apixaban), based on the discretion of the treating physician.

7. Demonstrated ability to tolerate dabigatran 150mg/BID (if CrCl >30ml/min), rivaroxaban 15mg QD (if CrCl 15-49 ml/min) and 20mg QD (if CrCl =50ml/min), or apixaban 5mg BID or 2.5 mg for subjects with =2 of the following: age = 80 years, body weight =60kg, serum creatinine =1.5 mg/dl.

8. Able and willing to provide written informed consent and willing to follow instructions, attend all required study visits, and undergo all planned tests.

9. Subject must be willing and able to discontinue oral anticoagulation for the purposes of this study

Exclusion Criteria:

Patients should not have any of the following criteria:

1. Permanent AF

2. Any documented single AF episode lasting = 1 hour per month over two consecutive months prior to study enrollment.

Mechanical prosthetic valves or severe valve disease.

3. CHADS2 score of 0, or > 2

4. Subject deemed high risk for non-cardioembolic stroke (i.e. significant carotid artery disease) based on discretion of the investigator.

5. Individual is pregnant, nursing, or planning to become pregnant.

6. Known hypersensitivity to non-Coumadin oral anticoagulants.

7. Documented prior stroke or transient ischemic attack.

8. Reversible causes of AF (e.g., cardiac surgery, pulmonary embolism, untreated hyperthyroidism).

9. Conditions associated with an increased risk of bleeding:

• Major surgery in the previous month

• Planned surgery or intervention in the next 3 months.

• History of intracranial, intraocular, spinal, retroperitoneal or atraumatic intra-articular bleeding

• Gastrointestinal hemorrhage within the past year unless the cause has been permanently eliminated (e.g. by surgery)

• Symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30 days

• Hemorrhagic disorder or bleeding diathesis

• Need for anticoagulant treatment for disorders other than AF

• Required use of non-aspirin antiplatelet agents (i.e., Plavix) at time of enrollment

• Uncontrolled hypertension (SBP >180 mmHg and/or DBP >100 mmHg)

10. Recent malignancy or radiation therapy (=6 months)

11. Anemia (hemoglobin <10g/dL) or thrombocytopenia (platelet count <100K/UL)

12. Patients who have received an investigational drug in the past 30 days or are participating in a drug study.

13. Intolerance or hypersensitivity to low dose aspirin therapy

14. Life expectancy less than the expected duration of the trial due to concomitant disease.

15. Any concomitant condition which, in the opinion of the investigator, would not allow safe participation in the study (e.g., drug addiction, alcohol abuse).

16. Inability to comply with daily data transmission requirements.

17. Known history of isolated atrial flutter/atrial tachycardia without atrial fibrillation.

18. More than 10 false positive atrial fibrillation events lasting > 30 minutes per month for two months prior to enrollment on a previously implantable cardiac monitor.

19. Severe renal impairment (CrCl < 15 ml/min)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• Non-coumadin Oral Anticoagulant
Administration of Non-coumadin Oral Anticoagulant for 30 days following episode of atrial fibrillation as detected by the Reveal XT device.

Locations

Country	Name	City	State
Canada	University of Western Ontario	London	Ontario
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
Northwestern University	Medtronic, National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Stroke Rate	To assess the stroke rate with implantable monitor-guided intermittent anticoagulation.	12 months	Yes
Other	Overall Survival	To assess the overall survival rate with implantable monitor-guided intermittent anticoagulation.	12 months	No
Other	Major Bleeding-free Survival Rate	To assess the major bleeding-free survival rate with implantable monitor-guided intermittent anticoagulation.	12 months	Yes
Other	Stroke-free Survival Rate	To assess the stroke-free survival rate with implantable monitor-guided intermittent anticoagulation.	12 months	Yes
Primary	Anticoagulant Utilization	Assess subject anticoagulant utilization and number of days on anticoagulation	up to 12 months	No
Secondary	Bleeding Incidence	To assess the bleeding incidence with implantable monitor-guided intermittent anticoagulation.	up to 12 months	Yes