Myocardial Infarction, Myocardial Infarction, Acute, Myocardial Infarction Old
Conditions
Brief summary
The BIO\|GUARD-MI study investigates whether continuous arrhythmia monitoring and the consequent treatment after detected arrhythmias in patients after myocardial infarction with preserved cardiac function, but other risk factors, decreases the risk of major adverse cardiac events.
Detailed description
Patients randomized to the BioMonitor arm will receive an implantable cardiac monitor (ICM; BioMonitor) with remote monitoring function (Home Monitoring®). If the device detects and reports an arrhythmia, patients will be appropriately examined and treated. Patients randomized to the control arm will receive best proven treatment, but no implantable cardiac monitor.
Interventions
DEVICEBioMonitor
Patients will be implanted with the BioMonitor + Home Monitoring feature
Sponsors
IHF GmbH - Institut für Herzinfarktforschung
Qmed Consulting A/S
Biotronik SE & Co. KG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Masking description
An independent Endpoint Committee was installed to evaluate all reported cardiovascular and serious AEs. The information provided to the Committee did not contain information about the group assigment of the patients.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Patient has a history of MI according to guidelines * CHA2DS2-VASc-Score ≥ 4 in men / ≥ 5 in women * LVEF \> 35 % as estimated within 6 months before enrollment but after conclusion of AMI treatment * Patient accepts activation of Home Monitoring® * Patient is able to understand the nature of the clinical study and has provided written informed consent
Exclusion criteria
* Patients with hemorrhagic diathesis * Permanent oral anticoagulation treatment for atrial fibrillation * Indication for chronic renal dialysis * Pacemaker or ICD implanted or indication for implantation * Parkinson's disease * Life expectancy \< 1 year * Participation in another interventional clinical Investigation * Age \< 18 years * Woman who are pregnant or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier Estimate of Percentage of Participants With Major Adverse Cardiac Event (MACE) | 2 years | The primary endpoint is defined as death for cardiovascular reasons or unplanned hospitalization for cardiovascular reasons as per study protocol. The time period with regards to the Time-to-Event Outcome Measures starts with the randomization of the patient. All patients will be assessed for Time-to-Event Outcome Measures until formal study termination is announced or until the individual patient meets a drop out criterion in accordance with the study protocol. The study period is estimated 6 years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier Estimate of Percentage of Participants With Outcome of Death Due to Any Cause | 2 years | The occurrence of death due to any cause will be recorded and analyzed. |
| Kaplan-Meier Estimate of Percentage of Participants With Outcome of Death Due to Any Cause or Heart Transplantation | 2 years | Assessment of the time from randomization to death for any reason or heart transplantation during the clinical investigation. |
| Kaplan-Meier Estimate of Percentage of Participants With Outcome of Cardiovascular Death or Heart Transplantation | 2 years | Assessment of the time from randomization to cardiovascular death or heart transplantation during the clinical investigation. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement. |
| Kaplan-Meier Estimate of Percentage of Participants With Worsening of Heart Failure Requiring Hospitalization or Urgent Visit | 2 years | Assessment of the time from randomization to first hospitalization or urgent visit for worsening of the patient status due to heart failure, or death due to heart failure. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement. |
| Kaplan-Meier Estimate of Percentage of Participants With an Arrhythmia Resulting in Hospitalization | 2 years | Assessment of the time from randomization to the first hospitalization resulting from an arrhythmia or death resulting from arrhythmia. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement. |
| Kaplan-Meier Estimate of Percentage of Participants With Acute Coronary Syndrome Resulting in Hospitalization | 2 years | Assessment of the time from randomization to the first hospitalization resulting from acute coronary syndrome or death resulting from acute coronary syndrome. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement. |
| Kaplan-Meier Estimate of Percentage of Participants With Major Bleeding Resulting in Hospitalization | 2 years | Assessment of the time from randomization to the first hospitalization resulting from major bleeding or death resulting from major bleeding. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement. |
| Kaplan-Meier Estimate of Percentage of Participants With Systemic Embolism Resulting in Hospitalization | 2 years | Assessment of the time from randomization to the first hospitalization resulting from systemic embolism or death resulting from systemic embolism. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement. |
| Kaplan-Meier Estimate of Percentage of Participants With an Arrhythmia | 2 years | Assessment of the time from randomization to first arrhythmia. |
| Type of Initiated Therapies | All data are collected for the period from randomization until official study end or drop-out, for all enrolled patients, up to 6 years. | Post-hoc categorical summary of most frequent therapies initiated after detection of arrhythmias. |
| Kaplan-Meier Estimate of Percentage of Participants Receiving Therapy After Arrhythmia Diagnosis | 2 years | Assessment of the time from randomization to first therapy. In this context therapy is the attempted remediation of the patient's regular heartbeat. |
| Change in World Health Organization Five Well-being Index (WHO-5) From 6 Months to 24 Months. | We report the intraindividual change from 6-months to 24-months. All data are collected for the period from randomization until official study end or drop-out, for all enrolled patients. | A further secondary endpoint is the assessment of the patient's well-being. The patient's well-being will be recorded during the regular telephone contacts using the WHO-5 Well-being Index. The scale reaches from 0 (worst status) to 100 (best possible status). |
| Kaplan-Meier Estimate of Percentage of Participants With Stroke Resulting in Hospitalization | 2 years | Assessment of the time from randomization to the first hospitalization resulting from stroke or death resulting from stroke. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean Value of EQ-5D-5L | From Baseline measurement to 60 months. All data are collected for the period from randomization until official study end or drop-out, for all enrolled patients. | The EQ-5D-5L questionnaire was administered during the telephone contacts to estimate utility values at different time points for an economic evaluation. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. The scale reaches from 0 (worst status) to 100 (best possible status). |
Countries
Australia, Austria, Belgium, Czechia, Denmark, France, Germany, Hungary, Latvia, Netherlands, Poland, Slovakia, Spain, United States
Participant flow
Pre-assignment details
802 patients were enrolled, 12 exited the study before randomization.
Participants by arm
| Arm | Count |
|---|---|
| BioMonitor Arm BioMonitor group (implantation with investigational device + transfer of information via Home Monitoring)
BioMonitor: Patients will be implanted with the BioMonitor + Home Monitoring feature | 398 |
| Control Arm Control group (standard of care) | 392 |
| Total | 790 |
Baseline characteristics
| Characteristic | BioMonitor Arm | Control Arm | Total |
|---|---|---|---|
| Age, Continuous | 71.5 years STANDARD_DEVIATION 7.7 | 70.8 years STANDARD_DEVIATION 8.5 | 71.2 years STANDARD_DEVIATION 8.1 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 107 Participants | 115 Participants | 222 Participants |
| Sex: Female, Male Male | 291 Participants | 277 Participants | 568 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 43 / 398 | 42 / 392 |
| other Total, other adverse events | 259 / 398 | 173 / 392 |
| serious Total, serious adverse events | 300 / 398 | 267 / 392 |
Outcome results
Primary
Kaplan-Meier Estimate of Percentage of Participants With Major Adverse Cardiac Event (MACE)
The primary endpoint is defined as death for cardiovascular reasons or unplanned hospitalization for cardiovascular reasons as per study protocol. The time period with regards to the Time-to-Event Outcome Measures starts with the randomization of the patient. All patients will be assessed for Time-to-Event Outcome Measures until formal study termination is announced or until the individual patient meets a drop out criterion in accordance with the study protocol. The study period is estimated 6 years.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BioMonitor Arm | Kaplan-Meier Estimate of Percentage of Participants With Major Adverse Cardiac Event (MACE) | 21.6 percentage of patients with event |
| Control Arm | Kaplan-Meier Estimate of Percentage of Participants With Major Adverse Cardiac Event (MACE) | 24.3 percentage of patients with event |
p-value: 0.2195% CI: [0.64, 1.1]Log Rank
Secondary
Change in World Health Organization Five Well-being Index (WHO-5) From 6 Months to 24 Months.
A further secondary endpoint is the assessment of the patient's well-being. The patient's well-being will be recorded during the regular telephone contacts using the WHO-5 Well-being Index. The scale reaches from 0 (worst status) to 100 (best possible status).
Time frame: We report the intraindividual change from 6-months to 24-months. All data are collected for the period from randomization until official study end or drop-out, for all enrolled patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BioMonitor Arm | Change in World Health Organization Five Well-being Index (WHO-5) From 6 Months to 24 Months. | 0.1 Change in units on the WHO-5 scale | Standard Deviation 17.6 |
| Control Arm | Change in World Health Organization Five Well-being Index (WHO-5) From 6 Months to 24 Months. | 0.7 Change in units on the WHO-5 scale | Standard Deviation 21.2 |
Secondary
Kaplan-Meier Estimate of Percentage of Participants Receiving Therapy After Arrhythmia Diagnosis
Assessment of the time from randomization to first therapy. In this context therapy is the attempted remediation of the patient's regular heartbeat.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BioMonitor Arm | Kaplan-Meier Estimate of Percentage of Participants Receiving Therapy After Arrhythmia Diagnosis | 53.6 percentage of patients with event |
| Control Arm | Kaplan-Meier Estimate of Percentage of Participants Receiving Therapy After Arrhythmia Diagnosis | 10.0 percentage of patients with event |
Secondary
Kaplan-Meier Estimate of Percentage of Participants With Acute Coronary Syndrome Resulting in Hospitalization
Assessment of the time from randomization to the first hospitalization resulting from acute coronary syndrome or death resulting from acute coronary syndrome. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BioMonitor Arm | Kaplan-Meier Estimate of Percentage of Participants With Acute Coronary Syndrome Resulting in Hospitalization | 10.6 percentage of patients with event |
| Control Arm | Kaplan-Meier Estimate of Percentage of Participants With Acute Coronary Syndrome Resulting in Hospitalization | 15.1 percentage of patients with event |
Secondary
Kaplan-Meier Estimate of Percentage of Participants With an Arrhythmia
Assessment of the time from randomization to first arrhythmia.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BioMonitor Arm | Kaplan-Meier Estimate of Percentage of Participants With an Arrhythmia | 53.6 percentage of patients with event |
| Control Arm | Kaplan-Meier Estimate of Percentage of Participants With an Arrhythmia | 10 percentage of patients with event |
Secondary
Kaplan-Meier Estimate of Percentage of Participants With an Arrhythmia Resulting in Hospitalization
Assessment of the time from randomization to the first hospitalization resulting from an arrhythmia or death resulting from arrhythmia. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BioMonitor Arm | Kaplan-Meier Estimate of Percentage of Participants With an Arrhythmia Resulting in Hospitalization | 3.3 percentage of patients with event |
| Control Arm | Kaplan-Meier Estimate of Percentage of Participants With an Arrhythmia Resulting in Hospitalization | 3.4 percentage of patients with event |
Secondary
Kaplan-Meier Estimate of Percentage of Participants With Major Bleeding Resulting in Hospitalization
Assessment of the time from randomization to the first hospitalization resulting from major bleeding or death resulting from major bleeding. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BioMonitor Arm | Kaplan-Meier Estimate of Percentage of Participants With Major Bleeding Resulting in Hospitalization | 0.6 percentage of patients with event |
| Control Arm | Kaplan-Meier Estimate of Percentage of Participants With Major Bleeding Resulting in Hospitalization | 1.1 percentage of patients with event |
Secondary
Kaplan-Meier Estimate of Percentage of Participants With Outcome of Cardiovascular Death or Heart Transplantation
Assessment of the time from randomization to cardiovascular death or heart transplantation during the clinical investigation. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BioMonitor Arm | Kaplan-Meier Estimate of Percentage of Participants With Outcome of Cardiovascular Death or Heart Transplantation | 3.5 percentage of patients with event |
| Control Arm | Kaplan-Meier Estimate of Percentage of Participants With Outcome of Cardiovascular Death or Heart Transplantation | 4.7 percentage of patients with event |
Secondary
Kaplan-Meier Estimate of Percentage of Participants With Outcome of Death Due to Any Cause
The occurrence of death due to any cause will be recorded and analyzed.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BioMonitor Arm | Kaplan-Meier Estimate of Percentage of Participants With Outcome of Death Due to Any Cause | 6.7 percentage of patients with event |
| Control Arm | Kaplan-Meier Estimate of Percentage of Participants With Outcome of Death Due to Any Cause | 7.1 percentage of patients with event |
Secondary
Kaplan-Meier Estimate of Percentage of Participants With Outcome of Death Due to Any Cause or Heart Transplantation
Assessment of the time from randomization to death for any reason or heart transplantation during the clinical investigation.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BioMonitor Arm | Kaplan-Meier Estimate of Percentage of Participants With Outcome of Death Due to Any Cause or Heart Transplantation | 6.7 percentage of patients with event |
| Control Arm | Kaplan-Meier Estimate of Percentage of Participants With Outcome of Death Due to Any Cause or Heart Transplantation | 7.1 percentage of patients with event |
Secondary
Kaplan-Meier Estimate of Percentage of Participants With Stroke Resulting in Hospitalization
Assessment of the time from randomization to the first hospitalization resulting from stroke or death resulting from stroke. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BioMonitor Arm | Kaplan-Meier Estimate of Percentage of Participants With Stroke Resulting in Hospitalization | 3.6 percentage of patients with event |
| Control Arm | Kaplan-Meier Estimate of Percentage of Participants With Stroke Resulting in Hospitalization | 3.0 percentage of patients with event |
Secondary
Kaplan-Meier Estimate of Percentage of Participants With Systemic Embolism Resulting in Hospitalization
Assessment of the time from randomization to the first hospitalization resulting from systemic embolism or death resulting from systemic embolism. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BioMonitor Arm | Kaplan-Meier Estimate of Percentage of Participants With Systemic Embolism Resulting in Hospitalization | 0.3 percentage of patients with event |
| Control Arm | Kaplan-Meier Estimate of Percentage of Participants With Systemic Embolism Resulting in Hospitalization | 0.7 percentage of patients with event |
Secondary
Kaplan-Meier Estimate of Percentage of Participants With Worsening of Heart Failure Requiring Hospitalization or Urgent Visit
Assessment of the time from randomization to first hospitalization or urgent visit for worsening of the patient status due to heart failure, or death due to heart failure. A specified endpoint definition will be given by the members of the EAEC and documented in the charter agreement.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BioMonitor Arm | Kaplan-Meier Estimate of Percentage of Participants With Worsening of Heart Failure Requiring Hospitalization or Urgent Visit | 6.0 percentage of patients with event |
| Control Arm | Kaplan-Meier Estimate of Percentage of Participants With Worsening of Heart Failure Requiring Hospitalization or Urgent Visit | 5.9 percentage of patients with event |
Secondary
Type of Initiated Therapies
Post-hoc categorical summary of most frequent therapies initiated after detection of arrhythmias.
Time frame: All data are collected for the period from randomization until official study end or drop-out, for all enrolled patients, up to 6 years.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BioMonitor Arm | Type of Initiated Therapies | Reduction of heart-rate lowering drugs | 43 Participants |
| BioMonitor Arm | Type of Initiated Therapies | Betablocker treatment | 13 Participants |
| BioMonitor Arm | Type of Initiated Therapies | Pacemaker implantation | 45 Participants |
| BioMonitor Arm | Type of Initiated Therapies | Antiarrhythmics | 10 Participants |
| BioMonitor Arm | Type of Initiated Therapies | Oral anticoagulation treatment | 84 Participants |
| Control Arm | Type of Initiated Therapies | Antiarrhythmics | 9 Participants |
| Control Arm | Type of Initiated Therapies | Oral anticoagulation treatment | 18 Participants |
| Control Arm | Type of Initiated Therapies | Pacemaker implantation | 6 Participants |
| Control Arm | Type of Initiated Therapies | Betablocker treatment | 6 Participants |
| Control Arm | Type of Initiated Therapies | Reduction of heart-rate lowering drugs | 5 Participants |
Other Pre-specified
Mean Value of EQ-5D-5L
The EQ-5D-5L questionnaire was administered during the telephone contacts to estimate utility values at different time points for an economic evaluation. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. The scale reaches from 0 (worst status) to 100 (best possible status).
Time frame: From Baseline measurement to 60 months. All data are collected for the period from randomization until official study end or drop-out, for all enrolled patients.
Population: Not all patients contributed to this endpoint. The EQ-5D-5L was only introduced later in the trial via an amendment in 2019.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BioMonitor Arm | Mean Value of EQ-5D-5L | Baseline | 74.9 Units on the EQ-5D-5L scale | Standard Deviation 16.4 |
| BioMonitor Arm | Mean Value of EQ-5D-5L | 12-months | 72.5 Units on the EQ-5D-5L scale | Standard Deviation 17.7 |
| BioMonitor Arm | Mean Value of EQ-5D-5L | 24-months | 71.6 Units on the EQ-5D-5L scale | Standard Deviation 18.2 |
| BioMonitor Arm | Mean Value of EQ-5D-5L | 36-months | 71.2 Units on the EQ-5D-5L scale | Standard Deviation 19.2 |
| BioMonitor Arm | Mean Value of EQ-5D-5L | 48-months | 69.9 Units on the EQ-5D-5L scale | Standard Deviation 17.3 |
| BioMonitor Arm | Mean Value of EQ-5D-5L | 60-months | 74.8 Units on the EQ-5D-5L scale | Standard Deviation 20.8 |
| Control Arm | Mean Value of EQ-5D-5L | 48-months | 69.8 Units on the EQ-5D-5L scale | Standard Deviation 19.2 |
| Control Arm | Mean Value of EQ-5D-5L | Baseline | 75.0 Units on the EQ-5D-5L scale | Standard Deviation 18.8 |
| Control Arm | Mean Value of EQ-5D-5L | 36-months | 69.5 Units on the EQ-5D-5L scale | Standard Deviation 18.4 |
| Control Arm | Mean Value of EQ-5D-5L | 12-months | 73.2 Units on the EQ-5D-5L scale | Standard Deviation 16.9 |
| Control Arm | Mean Value of EQ-5D-5L | 60-months | 64.4 Units on the EQ-5D-5L scale | Standard Deviation 21.2 |
| Control Arm | Mean Value of EQ-5D-5L | 24-months | 71.3 Units on the EQ-5D-5L scale | Standard Deviation 18.1 |