Management of Device Detected AT and Impact of Device Treatment Algorithms on Atrial Fibrillation (MANDATE-AF)

Management of Device Detected Atrial Tachyarrhythmia( AT) and Impact of Device Treatment Algorithms on Atrial Fibrillation (AF) in Indian Population

The MANDATE-AF study was designed to address evidence needs in India for device-based management of AF using AT/AF (Atrial Tachycardia/Atrial fibrillation) diagnostic features and therapies such as Reactive Atrial anti tachycardia Pacing (rATP) within Medtronic Cardiac Implantable Electronic Devices (CIED)and its impact on the time to persistent AF and progression of AT/AF.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiovascular Diseases
• Intervention / Treatment: Other: Treatment arm

Detailed Description

New generation Cardiac Implantable Electronic devices (CIED's)such as Pacemakers, Implantable Cardioverter Defibrillator (ICD) and Cardiac Resynchronization Therapy (CRT) has diagnostic and treatment delivery features which helps in slowing the progression of Atrial Fibrillation. A Study conducted in Europe, called the MINERVA Trial, showed the efficacy of a feature within Medtronic CIED's called (rATP)™, in the termination of abnormal rhythms by pacing stimuli, and clinical benefit in reducing incidence of Atrial Fibrillation. However, there is dearth of local evidence of this within the Indian population and also a need to show that turning on rATP does not compromise on battery depletion.

The MANDATE-AF study is a prospective , Interventional , Randomized, single blind study aiming to show that a reduced sequence programming of this rATP therapy ,can improve device battery longevity and is as effective as the Minerva trial ATP programming when it comes to showing its impact on time to persistent AF and on the progression of AT/AF within the Indian population.

The study analyses patients implanted with a Medtronic cardiac implantable device with an atrial lead and equipped with atrial ATP therapies.

The patients will be randomized into two groups:

• an interventional arm including patients with a conservative atrial ATP therapies programming setting
• a control, arm including patients with the same atrial ATP therapies programming setting adopted in the Minerva Trial

Cardiovascular events will be collected prospectively for at least 24 months after enrollment. Physicians will be recommended to schedule in clinic follow-up visits every 6 months and remote follow-up visits every 3 months in between. Every patient will be followed for at least 24 months, until the last patient enrolled exits the study.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110060
      • Sir Ganga Ram Hospital
    • New Delhi, Delhi, India
      • Fortis Escorts Heart Institute
  • Gujarat
    • Ahmedabad, Gujarat, India
      • Care Institute of medical sciences and research
  • Karnataka
    • Bangalore, Karnataka, India
      • Apollo Hospital , Bannerghatta
    • Mysore, Karnataka, India
      • Apollo BGS Hospital
  • Kerala
    • Kochi, Kerala, India
      • Aster Medicity
  • Odisha
    • Bhubaneshwar, Odisha, India
      • Apollo Hospital
  • Punjab
    • Mohali, Punjab, India
      • Fortis Escort Hospital
  • Rajasthan
    • Jaipur, Rajasthan, India
      • Eternal Heart Care center and Research
  • Tamil Nadu
    • Chennai, Tamil Nadu, India
      • Apollo Hospital
  • Telengana
    • Hyderabad, Telengana, India
      • Aig Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1 Subject is implanted with a Medtronic cardiac implantable device with an atrial lead equipped with atrial ATP therapies (rATP) enabled no longer than 18 months and at the minimum 6 weeks has passed since the implant; 2. Age > 55 years; 3. Subject provides informed consent; 4. Subject is willing and able to comply with the study procedures; 5. Subject has documented history of atrial fibrillation or atrial flutter, or one or more of the risk factors for developing AF as per AHA/HRS (American heart Association/Heart rhythm Society) guidelines.

• Age > 60 years;
• Stroke/TIA (Transient ischemic Attack);
• Diabetes;
• High Blood Pressure;
• Coronary artery disease;
• Cardiomyopathy;
• Pericardial inflammation;
• Prior heart attacks;
• Congestive heart failure;
• Structural heart disease (valve problems or congenital defects);
• Prior open-heart surgery;
• Untreated atrial flutter (another type of abnormal heart rhythm);
• Thyroid disease;
• Chronic lung disease;
• Sleep apnea;
• Excessive alcohol use;
• Serious illness or infection.

Exclusion criteria:

Patients are not eligible to be enrolled in the study if any of the following criteria is met:

1. Subject has been implanted with a Medtronic cardiac implantable device with an atrial lead equipped with atrial ATP therapies (rATP) enabled for more than 18 months;

2. Subject is in permanent AF or persistent AF at the baseline visit:

   1. The definition of permanent AF will be based on the physicians' decision that nothing further can be done to cardiovert the patient or, in historical cases, the investigators will refer to the Cardiac Compass reports:
   2. The definition of persistent AF at baseline will refer to the Cardiac Compass reports (>7 consecutive days in AF with the last day being the day of enrollment)
3. Participation in other studies which could potentially conflict with this study;
4. Legal incapacity or evidence that a subject cannot understand the purpose and risks of the study or inability to comply fully with study procedures and follow up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Control arm; The devices on the study are all commercially available and enabled with reactive ATP( rATP)feature, for the study both arms will have rATP switched on with one arm on the standard device setting or MINERVA setting ( control arm)
ACTIVE_COMPARATOR: Treatment arm; The devices on the study are all commercially available and enabled with reactive ATP( rATP)feature, for the study both arms will have rATP switched on with one arm on the reduced sequence programming ( treatment arm)	Other: Treatment arm; All pts are implanted with rATP enabled devices prior to the study start , the only intervention in both arms is switching on rATP and in the treatment arm programming changes done to optimize the rATP sequence delivery of therapy and prevent the patient from going into permanent or persistent AF; Other Names: programming changes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to persistent AF	time to persistent AF (defined as more than 7 continuous days of AF) or permanent AF	42months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause death(at the end of 24 months)	Compare the two atrial ATP Programming arms in terms of clinical endpoints such as deaths that occur on the study	42months
Number of Cardiovascular hospitalization	Compare the two atrial ATP Programming arms in terms of clinical endpoints such as cardiovascular hospitalizations (due to Heart Failure (HF), AF or other), as measured by the time to first event and annual rate of such events	42 Months
Annual rate for all-cause hospitalization	Compare the two atrial ATP Programming arms in terms of clinical endpoints such as all cause hospitalizations and its annual rate on the study	42 months
Measure the AT/AF burden metrics across various time points	Compare the two atrial ATP Programming arms in terms of clinical endpoints to evaluate the AT/AF burden metrics (amount of time each AF event lasts) as measured in terms of time to first event (daily burden ≥1 day, ≥2 days, ≥30 days) or the ratio between time in AT/AF and the observation period (the duration the patient is on the study)	42 months
Evaluate number of successful and unsuccessful treated AT/AF episodes out of the detected episodes	Compare the two atrial ATP Programming arms in terms of clinical endpoints to assess number of successful and unsuccessful treated AT/AF episodes out of detected episodes by the device .	42 months
Measure number of delivered therapies per episode	compare the two atrial ATP Programming arms in terms of clinical endpoints to measure the number of therapies delivered per episode to mitigate the AT/AF event.	42 months
Evaluate the number of ATP sequences	Compare the two ATP programming arms in terms of clinical endpoints to measure the number of ATP sequences delivered on each arm.	42 months
Evaluate number of stroke, TIA (Transient ischemic Attack ) or other thromboembolic events	compare the two atrial ATP Programming arms in terms of clinical endpoints to calculate number of stroke, TIA or other thromboembolic events reported on the study across both arms	42 months
Percentage of patients treated with anticoagulation therapy	Compare the two ATP programming arms in terms of clinical endpoints to evaluate the percentage of patients treated with anticoagulation therapy according to AF management guideline	42 months
Measure the LA diameter size	Compare the two ATP programming arms in terms of clinical endpoints to evaluate the LA diameter (if available) as measured through an Echocardiogram	42 months
Number of Pharmacological and electrical cardio versions reported	Compare the two ATP programming arms in terms of clinical endpoints such as number of electrical or pharmacological cardio-versions measured in terms of time to first event and its annual rate on the study;	42 months
Evaluate the biventricular pacing percentage	Compare the two ATP programming arms in terms of clinical endpoints such as biventricular pacing percentage (in cardiac resynchronization therapy defibrillator (CRT-D) / cardiac resynchronization therapy-Pacemaker (CRT-P) patients)	42 months
Incidence of the composite endpoints like death or Cardiovascular Hospitalizations	A cumulative endpoint which includes number of deaths, cardiovascular hospitalizations, stroke, TIA or other thromboembolic events.	42months
Incidence of persistent AF in patients with sick sinus syndrome	To evaluate the incidence of persistent AF in patients with sick sinus syndrome as compared to the one found in the Minerva trial, and characterize the difference between the European and Indian populations. The unit of measure will be number of pts that had persistent AF on the study.	42 months
Efficacy of Atrial ATP therapies measured by number of successful termination of AF events	To evaluate the efficacy of atrial ATP therapies as a function of the device type (Pacemakers(IPG),Cardiac defibrillators (ICD),Cardiac resynchronization Therapy (CRT-D, CRT-P), and population characteristics (baseline characteristics, implant indications) in optimizing therapy and evaluating the successful termination of AF events, preventing pts from going into persistent or permanent AF, as measured by no of ATP's delivered by device.	42 months

Collaborators and Investigators

• Sponsor: Medtronic Cardiac Rhythm and Heart Failure
• Investigators: Study Chair: Shantanu Sarkar, PhD, Medtronic, PLC

Publications and helpful links

General Publications

• Stewart S, Hart CL, Hole DJ, McMurray JJ. A population-based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley study. Am J Med. 2002 Oct 1;113(5):359-64. doi: 10.1016/s0002-9343(02)01236-6.
• Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, Van Gelder IC, Al-Attar N, Hindricks G, Prendergast B, Heidbuchel H, Alfieri O, Angelini A, Atar D, Colonna P, De Caterina R, De Sutter J, Goette A, Gorenek B, Heldal M, Hohloser SH, Kolh P, Le Heuzey JY, Ponikowski P, Rutten FH; ESC Committee for Practice Guidelines. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Europace. 2010 Oct;12(10):1360-420. doi: 10.1093/europace/euq350. No abstract available. Erratum In: Europace. 2011 Jul;13(7):1058. Dosage error in article text.
• Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001 May 9;285(18):2370-5. doi: 10.1001/jama.285.18.2370.
• Kannel WB, Wolf PA, Benjamin EJ, Levy D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol. 1998 Oct 16;82(8A):2N-9N. doi: 10.1016/s0002-9149(98)00583-9.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2019
• Primary Completion (ACTUAL): July 15, 2021
• Study Completion (ANTICIPATED): January 1, 2022

Study Registration Dates

• First Submitted: May 28, 2019
• First Submitted That Met QC Criteria: November 19, 2019
• First Posted (ACTUAL): November 21, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 27, 2021
• Last Update Submitted That Met QC Criteria: September 21, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Reactive ATP; device based Management of Atrial fibrilation; AF Management
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Cardiovascular Diseases; Atrial Fibrillation
• Other Study ID Numbers: MDT18039

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No