Mid-Q Response Study

Study Overview
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Brief Summary
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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.

Official Title
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Mid-Q Response Study

Conditions
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Heart Failure, Left Bundle-Branch Block, Heart Failure With Reduced Ejection Fraction (HFrEF), Heart Failure NYHA Class II, Heart Failure NYHA Class III, Heart Failure NYHA Class IV

Intervention / Treatment
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* Device: aCRT ON
* Device: aCRT OFF


Participation Criteria
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Eligibility Criteria
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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 exclusion criteria required by local law.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AdaptivCRT ON (aCRT ON, treatment group)<br>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. | Device: aCRT ON<br>* CRT device with AdaptivCRT enabled<br>|
| Active Comparator: AdaptivCRT OFF (aCRT OFF, control group)<br>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. | Device: aCRT OFF<br>* CRT device with AdaptivCRT disabled<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 6 months post-randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in New York Heart Association (NYHA) Class |  | Baseline to 6 and 12 months post-randomization | 
| Occurrence of hospitalizations for worsening heart failure | Defined as an event requiring inpatient hospitalization or invasive intervention | 12 months post-randomization | 
| All-cause and cardiovascular related mortality |  | 12 months post-randomization |