Cardiac Pacemaker, Artificial, Magnetic Resonance Imaging
Conditions
Brief summary
The purpose of the Advisa MRI System clinical study is to confirm safety and effectiveness in the clinical MRI (Magnetic Resonance Imaging) environment when subjects receive MRI scans up to 2W/kg Specific Absorption Rate (SAR) without positioning restrictions (MRI scans may occur anywhere on the body including the chest).
Detailed description
The Advisa MRI IPG is a dual chamber, multi-programmable IPG. The IPG is indicated to restore heart rates, improve cardiac output, prevent symptoms, or protect against arrhythmias related to cardiac impulse formation or conduction disorders. The IPG is indicated for use in patients who may benefit from rate-responsive pacing to support cardiac output during varying levels of activity and has been modified for use during an MRI exam. Subjects will have required follow-up visits after implant, at 2 months, 9-12 weeks, 3 months, 4 months, 6 months and every 6 months thereafter until the study ends. The MR scans will occur at the 9-12 weeks visit.
Interventions
DEVICEMedtronic Advisa MRI Implantable Pulse Generator (IPG)
Advisa MRI IPG is a dual chamber, multi-programmable IPG indicated to restore heart rates, improve cardiac output, prevent symptoms, or protect against arrhythmias related to cardiac impulse formation or conduction disorders. The IPG is indicated for use in patients who may benefit from rate-responsive pacing to support cardiac output during varying levels of activity and has been modified for use during an MRI exam.
DEVICEMedtronic CapSureFix MRI™ active fixation MRI lead
The Medtronic CapSureFix MRI™ active fixation MRI lead is a transvenous, bipolar, silicone, steroid eluting and active fixation pacing lead. It is based on the commercially available Medtronic Model 5076 lead and has been modified for use in the MRI environment. The MRI lead is used for both atrial and ventricular applications.
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Subjects who have a Class I or II indication for implantation of a dual chamber pacemaker according to the American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Rhythm Society (HRS) guidelines * Subjects who are able to undergo a pectoral implant * Subjects who are able and willing to undergo elective magnetic resonance (MR) scanning without sedation * Subjects who are geographically stable and available for follow-up at the study center for the length of the study
Exclusion criteria
* Subjects with a mechanical tricuspid heart valve * Subjects with a history of significant tricuspid valvular disease * Subjects for whom a single dose of 1.0 milligram (mg) dexamethasone acetate may be contraindicated * Subjects who require a legally authorized representative to obtain consent * Subjects who have a previously implanted pacemaker or implantable cardioverter defibrillator (ICD) (abandoned pacemaker and/or defibrillator leads are not permitted; however subjects with complete system explants are not excluded) * Subjects who are immediate candidates for an ICD * Subjects who require an indicated MR scan, other than those specifically described in the study, before the 4 months follow-up * Subjects with previously implanted active medical devices * Subjects with a non-MRI compatible device (such as ICDs or neurostimulators) or material implant (e.g. non-MRI compatible sternal wires, neurostimulators, biostimulators, metals or alloys) * Subjects with medical conditions that preclude the testing required by the protocol or limit study participation * Subjects who are enrolled or intend to participate in another clinical trial (of an investigational drug or device, new indication for an approved drug or device, or requirement of additional testing beyond standard clinical practice) during this clinical study * Pregnant women, or women of child bearing potential and who are not on a reliable form of birth control * Subjects with
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Magnetic Resonance Imaging (MRI)-Related Complications | MRI scan to one-month post-MRI scan | For each subject in this objective, the endpoint was the occurrence of an MRI-related complication within 30 days post-MRI. An independent Adverse Event Advisory Committee (AEAC) determined whether each adverse event was a complication and whether it was MRI-related. |
| Atrial Pacing Capture Threshold Success | Pre-MRI/waiting period to one month post-MRI/waiting period | Subjects' atrial pacing capture threshold was measured at the 9-12 week visit (pre-MRI/waiting period) and the 4-month visit (i.e. one month post-MRI/waiting period). A success was when a subject experienced an increase less than or equal to 0.5V (volts) between the two visits. |
| Ventricular Pacing Capture Threshold Success | Pre-MRI /waiting period to 1-month post-MRI/waiting period | Subjects' ventricular pacing capture threshold was measured at the 9-12 week visit (pre-MRI/waiting period) and the 4-month visit (i.e. one month post-MRI/waiting period). A success was when a subject experienced an increase less than or equal to 0.5V (volts) between the two visits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Atrial Sensed Amplitude Success | Pre-MRI /waiting period to 1-month post-MRI/waiting period | Subjects' atrial sensed amplitude was measured at the 9-12 week visit (pre-MRI/waiting period) and the 4-month visit (i.e. one month post-MRI/waiting period). A success was defined as a 50% or less decrease in atrial sensed amplitude between the two visits. |
| System-related Complications | Implant to four months post implant | Subjects with a complication related to the implanted system, which consisted of the pacemaker, leads to the right chambers of the heart (atrium and ventricle), pacemaker software, and programmer. All adverse events in the time frame were recorded at the subject's center and assessed the AEAC. The AEAC determined whether each adverse event was a complication (requiring invasive intervention), and whether the event was related to the system. |
| Ventricular Sensed Amplitude Success | Pre-MRI /waiting period to 1-month post-MRI/waiting period | Subjects' ventricular sensed amplitude was measured at the 9-12 week visit (pre-MRI/waiting period) and the 4-month visit (i.e. one month post-MRI/waiting period). A success was defined as a 50% or less decrease in ventricular sensed amplitude between the two visits. |
| Occurrence of Sustained Ventricular Arrhythmias and Asystole During MRI Scans. | During MRI scans | The endpoint was the occurrence of sustained ventricular arrhythmias and asystole during MRI scans and attributable to the MR scan. Sustained ventricular arrhythmias or asystole episodes that occurred during the MRI scan was considered attributable to the MR scan if so adjudicated by the AEAC. |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Hungary, Israel, Italy, Netherlands, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Enrollment occurred from June 22, 2010 to October 12, 2011. A total of 269 subjects were enrolled at 35 centers.
Pre-assignment details
A successful implant is defined as having a complete Advisa MRI system implant(Advisa MRI implable pulse generator (IPG) and two Model 5086MRI leads). Six subjects were exited prior to randomization. Of them, 3 subjects did not have an implant attempt and 3 subjects did not have a full Advisa MRI system. All other enrolled subjects were randomized.
Participants by arm
| Arm | Count |
|---|---|
| MRI Group Subjects randomized to the MRI group underwent a one-hour MRI scan, including 16 individual sequences in the chest and head region, at 9-12 weeks post-implant. | 177 |
| Control Group Subjects randomized to the Control group waited for one hour without having any MRI scan at 9-12 weeks post-implant. | 86 |
| Total | 263 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 1 |
Baseline characteristics
| Characteristic | MRI Group | Control Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 118 Participants | 62 Participants | 180 Participants |
| Age, Categorical Between 18 and 65 years | 59 Participants | 24 Participants | 83 Participants |
| Age Continuous | 68.1 years STANDARD_DEVIATION 12.8 | 68.7 years STANDARD_DEVIATION 10.8 | 68.3 years STANDARD_DEVIATION 12.2 |
| Region of Enrollment Australia | 15 participants | 5 participants | 20 participants |
| Region of Enrollment Canada | 5 participants | 3 participants | 8 participants |
| Region of Enrollment Europe | 112 participants | 56 participants | 168 participants |
| Region of Enrollment Middle East | 10 participants | 5 participants | 15 participants |
| Region of Enrollment United States | 35 participants | 17 participants | 52 participants |
| Sex: Female, Male Female | 68 Participants | 32 Participants | 100 Participants |
| Sex: Female, Male Male | 109 Participants | 54 Participants | 163 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 177 | 7 / 86 |
| serious Total, serious adverse events | 45 / 177 | 21 / 86 |
Outcome results
Primary
Atrial Pacing Capture Threshold Success
Subjects' atrial pacing capture threshold was measured at the 9-12 week visit (pre-MRI/waiting period) and the 4-month visit (i.e. one month post-MRI/waiting period). A success was when a subject experienced an increase less than or equal to 0.5V (volts) between the two visits.
Time frame: Pre-MRI/waiting period to one month post-MRI/waiting period
Population: To be included in the analysis, subjects in the MRI group must undergo an MRI scan and those in the Control group must complete the 9-12 week visit, and all the subjects must have valid pacing capture threshold measurements at pre-MRI/waiting period and the 4-month visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MRI Group | Atrial Pacing Capture Threshold Success | 141 participants |
| Control Group | Atrial Pacing Capture Threshold Success | 75 participants |
Comparison: Null hypothesis: % successes MRI group ≤ % successes Control group -10%.Farrington-Manning test
Primary
Magnetic Resonance Imaging (MRI)-Related Complications
For each subject in this objective, the endpoint was the occurrence of an MRI-related complication within 30 days post-MRI. An independent Adverse Event Advisory Committee (AEAC) determined whether each adverse event was a complication and whether it was MRI-related.
Time frame: MRI scan to one-month post-MRI scan
Population: Subjects who had an MRI scan and completed their 4-month visit (or a later follow-up), or had an MRI-related complication within one month post-MRI were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MRI Group | Magnetic Resonance Imaging (MRI)-Related Complications | 0 participants |
Comparison: Null Hypothesis: MRI-related complication rate between the MRI scan and one-month post-MRI \>=10%.p-value: <0.0001exact test of binomial proportions
Primary
Ventricular Pacing Capture Threshold Success
Subjects' ventricular pacing capture threshold was measured at the 9-12 week visit (pre-MRI/waiting period) and the 4-month visit (i.e. one month post-MRI/waiting period). A success was when a subject experienced an increase less than or equal to 0.5V (volts) between the two visits.
Time frame: Pre-MRI /waiting period to 1-month post-MRI/waiting period
Population: To be included in the analysis, subjects in the MRI group must undergo an MRI scan and those in the Control group must complete the 9-12 week visit, and all the subjects must have valid pacing capture threshold measurements at pre-MRI/waiting period and the 4-month visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MRI Group | Ventricular Pacing Capture Threshold Success | 146 participants |
| Control Group | Ventricular Pacing Capture Threshold Success | 78 participants |
Comparison: Null hypothesis: % successes MRI group ≤ % successes Control group -10%.p-value: <0.000195% CI: [-5, 5.9]Farrington-Manning test
Secondary
Atrial Sensed Amplitude Success
Subjects' atrial sensed amplitude was measured at the 9-12 week visit (pre-MRI/waiting period) and the 4-month visit (i.e. one month post-MRI/waiting period). A success was defined as a 50% or less decrease in atrial sensed amplitude between the two visits.
Time frame: Pre-MRI /waiting period to 1-month post-MRI/waiting period
Population: Only subjects with measured sensed amplitude values at both pre-MRI/waiting period and the 4-month visit were used in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MRI Group | Atrial Sensed Amplitude Success | 134 participants |
| Control Group | Atrial Sensed Amplitude Success | 72 participants |
Comparison: Null hypothesis: % successes MRI group ≤ % successes Control group - 10%.p-value: 0.001Farrington-Manning test
Secondary
Occurrence of Sustained Ventricular Arrhythmias and Asystole During MRI Scans.
The endpoint was the occurrence of sustained ventricular arrhythmias and asystole during MRI scans and attributable to the MR scan. Sustained ventricular arrhythmias or asystole episodes that occurred during the MRI scan was considered attributable to the MR scan if so adjudicated by the AEAC.
Time frame: During MRI scans
Population: All subjects successfully implanted with the Advisa MRI system who underwent MRI scans were included in the analysis. All MRI scans, whether done at the 9-12 week visit in the MRI group, or done at other times in either group were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MRI Group | Occurrence of Sustained Ventricular Arrhythmias and Asystole During MRI Scans. | 0 participants |
Comparison: Null hypothesis: the proportion of subjects with sustained ventricular arrhythmias and asystole during MRI scans \>= 10%.p-value: <0.0001exact test of binomial proportions
Secondary
System-related Complications
Subjects with a complication related to the implanted system, which consisted of the pacemaker, leads to the right chambers of the heart (atrium and ventricle), pacemaker software, and programmer. All adverse events in the time frame were recorded at the subject's center and assessed the AEAC. The AEAC determined whether each adverse event was a complication (requiring invasive intervention), and whether the event was related to the system.
Time frame: Implant to four months post implant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MRI Group | System-related Complications | 20 participants |
Comparison: Null hypothesis: the system-related complication rate between the implant procedure and the 4-months visit \>= 20%.p-value: <0.05Kaplan-Meier method
Secondary
Ventricular Sensed Amplitude Success
Subjects' ventricular sensed amplitude was measured at the 9-12 week visit (pre-MRI/waiting period) and the 4-month visit (i.e. one month post-MRI/waiting period). A success was defined as a 50% or less decrease in ventricular sensed amplitude between the two visits.
Time frame: Pre-MRI /waiting period to 1-month post-MRI/waiting period
Population: Only subjects with measured sensed amplitude values at both pre-MRI/waiting period and the 4-month visit were used in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MRI Group | Ventricular Sensed Amplitude Success | 138 participants |
| Control Group | Ventricular Sensed Amplitude Success | 74 participants |
Comparison: Null hypothesis: % successes MRI group ≤ % successes Control group - 10%.p-value: 0.0001Farrington-Manning test