Heart Failure, Heart Failure NYHA Class II, Heart Failure NYHA Class III, Heart Failure NYHA Class IV, Heart Failure With Reduced Ejection Fraction (HFrEF), Left Bundle-Branch Block
Conditions
Brief summary
The Mid-Q Response study is a prospective, multi-center, randomized controlled, interventional, single-blinded, post-market study. The purpose of the Mid-Q Response study is to test the hypothesis that the AdaptivCRT (aCRT) algorithm is superior to standard CRT therapy regarding patient outcomes in CRT indicated patients with moderate QRS duration, preserved atrioventricular (AV) conduction and left bundle branch block (LBBB). The study will be executed at approximately 60 centers in Asia. The subjects will be randomly assigned in a 1:1 ratio to the aCRT ON (Adaptive Bi-V and LV) group or the aCRT OFF (Nonadaptive CRT) group. The primary objective is to test the hypothesis that aCRT ON increases the proportion of patients that improve on the Clinical Composite Score (CCS) compared to aCRT OFF at 6 months of follow-up.
Interventions
Sponsors
Medtronic
Medtronic Japan Co., Ltd.
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Intervention model description
Eligible subjects will be randomized after baseline assessment and implant of a CRT system containing the aCRT algorithm. Randomization will be done in a 1:1 ratio to either treatment (aCRT ON, Adaptive Bi-V and LV) or control (aCRT OFF, Nonadaptive CRT) groups. All subjects, independent of randomization assignment, will have a CRT system.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is willing to sign and date the study Informed Consent Form (ICF). * Subject is indicated for a CRT device according to local guidelines. * Subject has sinus rhythm at time of enrollment * Subject has a moderately wide intrinsic QRS duration ≥120 ms and \<150 ms * Subject has Left Bundle Branch Block (LBBB) as documented on an ECG (preferably within 30 days prior to enrollment but up to 50 days is accepted) with Qs or rS in leads V1 and V2, and Mid-QRS notching or slurring in ≥2 of leads V1, V2, V5, V6, I, and aVL * Subject has intrinsic, normal AV conduction as documented on an ECG by a PR interval ≤200 ms (preferably within 30 days prior to enrollment but up to 50 days is accepted). * Subject has left ventricular ejection fraction ≤35% (documented within 180 days prior to enrollment). * Subject has NYHA class II, III, or IV (documented within 30 days prior to enrollment) despite optimal medical therapy. Optimal medical therapy is defined as maximal tolerated dose of Beta-blockers and a therapeutic dose of ACE-I, ARB or MRA.
Exclusion criteria
* Subject is less than 18 years of age (or has not reached minimum age per local law if that is higher). * Subject is not expected to remain available for at least 1 year of follow-up visits. * Subjects has permanent atrial arrhythmias for which pharmacological therapy and/or cardioversion have been unsuccessful or have not been attempted. * Subject is, or previously has been, receiving cardiac resynchronization therapy. * Subject is currently enrolled or planning to participate in a potentially confounding drug or device trial during the course of this study. Co-enrollment in concurrent trials is only allowed when documented pre-approval is obtained from the Medtronic study manager. * Subject has unstable angina, or experienced an acute myocardial infarction (MI) or received coronary artery revascularization (CABG) or coronary angioplasty (PTCA) within 30 days prior to enrollment. * Subject has a mechanical tricuspid heart valve or is scheduled to undergo valve repair or valve replacement during the course of the study. * Subject is post heart transplant (subjects on the heart transplant list for the first time are not excluded). * Subject has a limited life expectancy due to non-cardiac causes that would not allow completion of the study. * Subject is pregnant (if required by local law, women of child-bearing potential must undergo a pregnancy test within seven days prior to device implant). * Subject meets any
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Composite Score | 6 months post-randomization | The Clinical Composite Score (CCS) classifies patients according their clinical status at 6 months post-randomization into categories Improved, Unchanged, and Worsened. A patient is classified Worsened in case of death, hospitalization for worsening heart failure, worsened New York Heart Association (NYHA) class (using last observation carried forward), or worsened status on the Global Assessment Score. Also, patients that exit the study or cross over because of worsening heart failure are classified Worsened. A patient is classified Improved when not Worsened and there is an improvement in NYHA class or Global Assessment Score. Patients that are not Worsened or Improved are Unchanged including all patients that miss NYHA class and Global Assessment Score data and are not classified Worsened because of death, HF hospitalization, exit or crossover. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in New York Heart Association (NYHA) Class | Baseline to 6 and 12 months post-randomization | NYHA class is an ordinal variable with higher classes indicating a worse degree of heart failure: Class I - No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc. Class II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. Class III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m).Comfortable only at rest. Class IV - Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients. |
| Occurrence of Hospitalizations for Worsening Heart Failure | 12 months post-randomization | Defined as an event requiring inpatient hospitalization or invasive intervention |
| All-cause Mortality | 12 months post-randomization | All-cause mortality in the aCRT ON group vs the aCRT OFF group |
| Cardiovascular-related Mortality | 12 months post-randomization | Defined as all cardiac deaths as well as any cardiovascular deaths that are not directly a result of mechanical or electrical heart dysfunction. |
Countries
Brunei, China, Hong Kong, Indonesia, Japan, Malaysia, Philippines, Singapore, South Korea, Taiwan
Participant flow
Recruitment details
The study was multicentric and in a hospital setting, patients selected were heart failure patients in Asian countries indicated for CRT per local guidelines with moderately wide QRS (duration ≥120ms and \<150ms), preserved AV conduction (PR interval ≤ 200 ms), along with a Left bundle branch block (LBBB).
Pre-assignment details
Patients were enrolled as long as they met the inclusion criteria and were willing to consent. A total of 177 subjects were enrolled, of which 171 subjects were randomized between Adaptive and Conventional CRT.
Participants by arm
| Arm | Count |
|---|---|
| AdaptivCRT ON (aCRT ON, Treatment Group) AdaptivCRT programmed to Adaptive Bi-V and LV The aCRT algorithm has been developed to provide RV-synchronized LV pacing when intrinsic AV conduction is normal or BiV pacing otherwise.
aCRT ON: CRT device with AdaptivCRT enabled | 86 |
| AdaptivCRT OFF (aCRT OFF, Control Group) AdaptivCRT programmed to Nonadaptive CRT (standard CRT). Control group subjects will be optimized per physician's discretion. The method of AV and VV optimization in the control group will be collected.
aCRT OFF: CRT device with AdaptivCRT disabled | 85 |
| Total | 171 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 5 | 6 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | AdaptivCRT ON (aCRT ON, Treatment Group) | AdaptivCRT OFF (aCRT OFF, Control Group) | Total |
|---|---|---|---|
| Age, Continuous | 67.0 years STANDARD_DEVIATION 11.3 | 65.8 years STANDARD_DEVIATION 13.7 | 66.4 years STANDARD_DEVIATION 12.5 |
| LVEF | 27.0 percent STANDARD_DEVIATION 6.6 | 25.2 percent STANDARD_DEVIATION 6.5 | 26.1 percent STANDARD_DEVIATION 6.6 |
| NYHA class NYHA class I | 1 Participants | 1 Participants | 2 Participants |
| NYHA class NYHA class II | 30 Participants | 31 Participants | 61 Participants |
| NYHA class NYHA class IIII | 52 Participants | 47 Participants | 99 Participants |
| NYHA class NYHA class IV | 3 Participants | 6 Participants | 9 Participants |
| PR interval | 173.2 ms STANDARD_DEVIATION 21 | 174.3 ms STANDARD_DEVIATION 21.4 | 173.7 ms STANDARD_DEVIATION 21.1 |
| QRS duration | 136.9 ms STANDARD_DEVIATION 9.4 | 136.1 ms STANDARD_DEVIATION 9 | 136.5 ms STANDARD_DEVIATION 9.2 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 29 Participants | 25 Participants | 54 Participants |
| Sex: Female, Male Male | 57 Participants | 60 Participants | 117 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 86 | 6 / 85 |
| other Total, other adverse events | 8 / 86 | 14 / 85 |
| serious Total, serious adverse events | 27 / 86 | 24 / 85 |
Outcome results
Primary
Clinical Composite Score
The Clinical Composite Score (CCS) classifies patients according their clinical status at 6 months post-randomization into categories Improved, Unchanged, and Worsened. A patient is classified Worsened in case of death, hospitalization for worsening heart failure, worsened New York Heart Association (NYHA) class (using last observation carried forward), or worsened status on the Global Assessment Score. Also, patients that exit the study or cross over because of worsening heart failure are classified Worsened. A patient is classified Improved when not Worsened and there is an improvement in NYHA class or Global Assessment Score. Patients that are not Worsened or Improved are Unchanged including all patients that miss NYHA class and Global Assessment Score data and are not classified Worsened because of death, HF hospitalization, exit or crossover.
Time frame: 6 months post-randomization
Population: All randomized subjects
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AdaptivCRT ON (aCRT ON, Treatment Group) | Clinical Composite Score | Unchanged | 10 Participants |
| AdaptivCRT ON (aCRT ON, Treatment Group) | Clinical Composite Score | Improved | 66 Participants |
| AdaptivCRT ON (aCRT ON, Treatment Group) | Clinical Composite Score | Worsened | 10 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Clinical Composite Score | Improved | 68 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Clinical Composite Score | Unchanged | 11 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Clinical Composite Score | Worsened | 6 Participants |
p-value: 0.61Chi-squared
Secondary
All-cause Mortality
All-cause mortality in the aCRT ON group vs the aCRT OFF group
Time frame: 12 months post-randomization
Population: All randomized subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AdaptivCRT ON (aCRT ON, Treatment Group) | All-cause Mortality | 5 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | All-cause Mortality | 6 Participants |
p-value: 0.78Log Rank
Secondary
Cardiovascular-related Mortality
Defined as all cardiac deaths as well as any cardiovascular deaths that are not directly a result of mechanical or electrical heart dysfunction.
Time frame: 12 months post-randomization
Population: All randomized subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AdaptivCRT ON (aCRT ON, Treatment Group) | Cardiovascular-related Mortality | 3 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Cardiovascular-related Mortality | 3 Participants |
p-value: 0.9895% CI: [0.206, 5.056]Regression, Cox
Secondary
Change in New York Heart Association (NYHA) Class
NYHA class is an ordinal variable with higher classes indicating a worse degree of heart failure: Class I - No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc. Class II - Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. Class III - Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m).Comfortable only at rest. Class IV - Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.
Time frame: Baseline to 6 and 12 months post-randomization
Population: All randomized subjects
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| AdaptivCRT ON (aCRT ON, Treatment Group) | Change in New York Heart Association (NYHA) Class | Baseline | Class I | 1 Participants |
| AdaptivCRT ON (aCRT ON, Treatment Group) | Change in New York Heart Association (NYHA) Class | Baseline | Class II | 30 Participants |
| AdaptivCRT ON (aCRT ON, Treatment Group) | Change in New York Heart Association (NYHA) Class | Baseline | Class III/IV | 55 Participants |
| AdaptivCRT ON (aCRT ON, Treatment Group) | Change in New York Heart Association (NYHA) Class | 3 Month | Class III/IV | 11 Participants |
| AdaptivCRT ON (aCRT ON, Treatment Group) | Change in New York Heart Association (NYHA) Class | 3 Month | Not reported | 2 Participants |
| AdaptivCRT ON (aCRT ON, Treatment Group) | Change in New York Heart Association (NYHA) Class | 6 Month | Class I | 23 Participants |
| AdaptivCRT ON (aCRT ON, Treatment Group) | Change in New York Heart Association (NYHA) Class | 6 Month | Class II | 50 Participants |
| AdaptivCRT ON (aCRT ON, Treatment Group) | Change in New York Heart Association (NYHA) Class | 6 Month | Class III/IV | 11 Participants |
| AdaptivCRT ON (aCRT ON, Treatment Group) | Change in New York Heart Association (NYHA) Class | 6 Month | Not reported | 2 Participants |
| AdaptivCRT ON (aCRT ON, Treatment Group) | Change in New York Heart Association (NYHA) Class | 12 Month | Class I | 35 Participants |
| AdaptivCRT ON (aCRT ON, Treatment Group) | Change in New York Heart Association (NYHA) Class | 12 Month | Class III/IV | 8 Participants |
| AdaptivCRT ON (aCRT ON, Treatment Group) | Change in New York Heart Association (NYHA) Class | 12 Month | Not reported | 2 Participants |
| AdaptivCRT ON (aCRT ON, Treatment Group) | Change in New York Heart Association (NYHA) Class | Baseline | Not reported | 0 Participants |
| AdaptivCRT ON (aCRT ON, Treatment Group) | Change in New York Heart Association (NYHA) Class | 3 Month | Class I | 24 Participants |
| AdaptivCRT ON (aCRT ON, Treatment Group) | Change in New York Heart Association (NYHA) Class | 3 Month | Class II | 49 Participants |
| AdaptivCRT ON (aCRT ON, Treatment Group) | Change in New York Heart Association (NYHA) Class | 12 Month | Class II | 41 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Change in New York Heart Association (NYHA) Class | Baseline | Not reported | 0 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Change in New York Heart Association (NYHA) Class | Baseline | Class I | 1 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Change in New York Heart Association (NYHA) Class | 12 Month | Class I | 32 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Change in New York Heart Association (NYHA) Class | 3 Month | Class I | 22 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Change in New York Heart Association (NYHA) Class | Baseline | Class III/IV | 53 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Change in New York Heart Association (NYHA) Class | 3 Month | Class II | 53 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Change in New York Heart Association (NYHA) Class | 12 Month | Class III/IV | 9 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Change in New York Heart Association (NYHA) Class | 3 Month | Class III/IV | 4 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Change in New York Heart Association (NYHA) Class | 12 Month | Class II | 42 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Change in New York Heart Association (NYHA) Class | 3 Month | Not reported | 6 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Change in New York Heart Association (NYHA) Class | 12 Month | Not reported | 2 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Change in New York Heart Association (NYHA) Class | 6 Month | Class I | 27 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Change in New York Heart Association (NYHA) Class | Baseline | Class II | 31 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Change in New York Heart Association (NYHA) Class | 6 Month | Class II | 52 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Change in New York Heart Association (NYHA) Class | 6 Month | Not reported | 3 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Change in New York Heart Association (NYHA) Class | 6 Month | Class III/IV | 3 Participants |
Comparison: Due to limited number of subjects with NYHA class III or IV during follow-up, class III, IV, and death were grouped as a single category for analysis.p-value: 0.6395% CI: [0.579, 2.455]Regression, Logistic
Secondary
Occurrence of Hospitalizations for Worsening Heart Failure
Defined as an event requiring inpatient hospitalization or invasive intervention
Time frame: 12 months post-randomization
Population: All randomized subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AdaptivCRT ON (aCRT ON, Treatment Group) | Occurrence of Hospitalizations for Worsening Heart Failure | 10 Participants |
| AdaptivCRT OFF (aCRT OFF, Control Group) | Occurrence of Hospitalizations for Worsening Heart Failure | 8 Participants |
p-value: 0.6495% CI: [0.492, 3.175]Regression, Cox