Cardiovascular Diseases
Conditions
Keywords
Reactive ATP, device based Management of Atrial fibrilation, AF Management
Brief summary
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.
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.
Interventions
OTHERTreatment 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
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
The patient is unaware of which type of programming changes have been made ( whether it is the reduced sequence programming or the standard Minerva setting )
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of 'Persistent AF' Over Time | up to 18 months | Probability of participants to encounter 'Persistant AF" was analyzed over time. This information is obtained using Kaplan-Meier method. The occurrence of Persistant AF has been studied over time by using Kaplan-Meier technique. Probabilities and their 95% confidence intervals have been obtained at baseline, 6 months, 12 months and 18 months. We are studying the occurrence of Persistant AF based on results obtained from the Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of All-cause Death Over Time | up to 18 months | Probability of participants to encounter 'All-cause death was analyzed over time. This information is obtained using Kaplan-Meier method. The occurrence of All-cause death has been studied over time by using Kaplan-Meier technique. Probabilities and their 95% confidence intervals have been obtained at baseline, 6 months, 12 months and 18 months. We are studying the occurrence of All-cause death based on results obtained from the Kaplan-Meier method. |
| Cardiovascular Hospitalization | 18 Months | 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. No CV related hospitalization events were observed. This information is obtained using the Kaplan-Meier method. The incidence of CV hospitalization has been studied using the Kaplan-Meier technique. Incidence rates and their 95% confidence intervals have been obtained at baseline, 6 months, 12 months and 18 months.' |
| Annual Rate for All-cause Hospitalization | 18 months | Compare the two atrial ATP Programming arms in terms of clinical endpoints such as all cause hospitalizations and its annual rate on the study |
| Incidence of AT/AF Burden ≥ 1day Overtime | up to 18 months | Probability of participants to encounter AT/AF Burden ≥ 1day was analyzed over time. This information is obtained using Kaplan-Meier method. The occurrence of AT/AF Burden ≥ 1day has been studied over time by using Kaplan-Meier technique. Probabilities and their 95% confidence intervals have been obtained at baseline, 6 months, 12 months and 18 months. We are studying the occurrence of AT/AF Burden ≥ 1day based on results obtained from the Kaplan-Meier method. |
| Incidence of AT/AF Burden ≥ 30 Days Overtime | up to 18 months | Probability of participants to encounter AT/AF Burden ≥ 30 days was analyzed over time. This information is obtained using Kaplan-Meier method. The occurrence of 'AT/AF Burden ≥ 30 days has been studied over time by using Kaplan-Meier technique. Probabilities and their 95% confidence intervals have been obtained at baseline, 6 months, 12 months and 18 months. We are studying the occurrence of AT/AF Burden ≥ 30 days based on results obtained from the Kaplan-Meier method. |
| Incidence of AT/AF Burden ≥ 2 Days Overtime | up to 18 months | Probability of participants to encounter AT/AF Burden ≥ 2 days was analyzed over time. This information is obtained using Kaplan-Meier method. The occurrence of AT/AF Burden ≥ 2 days has been studied over time by using Kaplan-Meier technique. Probabilities and their 95% confidence intervals have been obtained at baseline, 6 months, 12 months and 18 months. We are studying the occurrence of AT/AF Burden ≥ 2 days based on results obtained from the Kaplan-Meier method. |
| Evaluate Number of Successful and Unsuccessful Treated AT/AF Episodes Out of the Detected Episodes | 18 months | 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 . |
| Measure Number of Delivered Therapies Per Episode | 18 months | Compare the two ATP programming arms in terms of clinical endpoints to measure the average number of ATP sequences delivered per patient on each arm |
| Evaluate the Number of ATP Sequences | 18 months | Compare the two ATP programming arms in terms of clinical endpoints to measure the number of ATP sequences delivered on each arm. |
| Evaluate Number of Stroke, TIA (Transient Ischemic Attack ) or Other Thromboembolic Events | 18 months | 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 |
| Percentage of Patients Treated With Anticoagulation Therapy | 18 months | 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. |
| Measure the Left Atrial Diameter Size | up to 18 months | Compare the two ATP programming arms in terms of clinical endpoints to evaluate the Left Atrial diameter (if available) as measured through an Echocardiogram |
| Number of Pharmacological and Electrical Cardio Versions Reported | 18 months | 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; |
| Evaluate the Biventricular Pacing Percentage (Average) | 18 months | 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) |
| Incidence of the Composite Endpoints Like Death or Cardiovascular Hospitalizations | 42months | A cumulative endpoint which includes number of deaths, cardiovascular hospitalizations, stroke, TIA or other thromboembolic events. |
| Incidence of Persistent AF in Patients With Sick Sinus Syndrome | 42 months | 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. |
| Efficacy of Atrial ATP Therapies Measured by Number of Successful Termination of AF Events | 42 months | 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. |
Countries
India
Contacts
STUDY_CHAIRShantanu Sarkar, PhD
Medtronic, PLC
Participant flow
Recruitment details
The study was multicentric and in a hospital setting, patients were selected based on retrospective data . The study recruitment lasted from 1 Oct 2019 till 30 May 2021 even though the LPE was 5 Feb 2021. The recruitment period ended earlier than initially planned (18 months expected) due to the decision to early terminate the study due to Covid impact.
Pre-assignment details
The study was based on Standard of Care practice and all of the pts were previously implanted with the device, so they were enrolled as long as they met the inclusion criteria and Pt was willing to consent . A total of 79 subjects were enrolled, of which 75 were eligible and randomized.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 71 years |
| BMI | 24.7 kg/m2 |
| cha2ds2-vasc score missing information | 17 Participants |
| cha2ds2-vasc score score of 0 | 0 Participants |
| cha2ds2-vasc score score of 1 | 4 Participants |
| cha2ds2-vasc score score of 2 | 10 Participants |
| cha2ds2-vasc score score of 3 | 9 Participants |
| cha2ds2-vasc score score of 4 | 3 Participants |
| Diastolic BP | 70.0 mmHg |
| Hearth Rate | 71 beats/min |
| Height | 165.0 cm |
| Race and Ethnicity Not Collected | 0 Participants |
| Region of Enrollment India | 38 participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 26 Participants |
| Systolic BP | 130.0 mmHg |
| Weight | 68.9 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 1 / 37 |
| other Total, other adverse events | 0 / 38 | 0 / 37 |
| serious Total, serious adverse events | 1 / 38 | 2 / 37 |
Outcome results
None listed