Clinical trial NCT01706146: Rhythm Evaluation for AntiCoagulaTion With COntinuous Monitoring
Official title: Rhythm Evaluation for AntiCoagulaTion With COntinuous Monitoring
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atrial Fibrillation
Keywords: atrial fibrillation
reveal xt
oral anticoagulation
dabigatran
rivaroxaban
apixaban
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Medtronic
First posted: 2012-10-15
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Number of Days on Anticoagulation
timeFrame: up to 12 months
Secondary outcomes:
measure: Bleeding Incidence
timeFrame: up to 12 months
Other outcomes:
measure: Stroke Rate
timeFrame: 12 months
measure: Overall Survival
timeFrame: 12 months
measure: Major Bleeding-free Survival Rate
timeFrame: 12 months
measure: Stroke-free Survival Rate
timeFrame: 12 months
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: London
country: Canada
facility: University of Western Ontario
state: Ontario
Study officials:
affiliation: Northwestern University
name: Alexandru Chicos, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Passman R, Leong-Sit P, Andrei AC, Huskin A, Tomson TT, Bernstein R, Ellis E, Waks JW, Zimetbaum P. Targeted Anticoagulation for Atrial Fibrillation Guided by Continuous Rhythm Assessment With an Insertable Cardiac Monitor: The Rhythm Evaluation for Anticoagulation With Continuous Monitoring (REACT.COM) Pilot Study. J Cardiovasc Electrophysiol. 2016 Mar;27(3):264-70. doi: 10.1111/jce.12864. Epub 2015 Nov 23.