Mid-Q Response Study

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure; Left Bundle-Branch Block; Heart Failure NYHA Class II; Heart Failure NYHA Class III; Heart Failure NYHA Class IV; Heart Failure With Reduced Ejection Fraction (HFrEF)
• Intervention / Treatment: Device: aCRT ON; Device: aCRT OFF

• Study Type: Interventional
• Enrollment (Estimated): 232
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Federica La Neve, PhD; Phone Number: +39 3476190843; Email: federica.laneve@medtronic.com

Study Locations

• Brunei Darussalam
  • Bandar Seri Begawan, Brunei Darussalam
    • Gleneagles Jerudong Park Medical Centre
• China
  • Shanghai, China
    • Ruijin Hospital Shanghai Jiao Tong University School of Medicine
• Hong Kong
  • Hong Kong, Hong Kong
    • Tuen Mun Hospital
  • Hong Kong, Hong Kong
    • Queen Elizabeth Hospital
  • Hong Kong, Hong Kong
    • Grantham Hospital
• Indonesia
  • Jakarta, Indonesia, 11420
    • National Cardiovascular Center Harapan Kita
• Japan
  • Fukui, Japan
    • University of Fukui Hospital
  • Fukuoka, Japan
    • Kokura Memorial Hospital
  • Hirosaki, Japan
    • Hirosaki University Hospital
  • Hiroshima, Japan
    • Hiroshima Prefectural Hospital
  • Hyōgo, Japan
    • The Hospital of Hyogo College of Medicine
  • Ibaraki, Japan
    • University of Tsukuba Hospital
  • Isehara, Japan
    • Tokai University Hospital
  • Kanagawa, Japan
    • Kitasato University Hospital
  • Kawasaki, Japan
    • St. Marianna University School of Medicine Hospital
  • Kumamoto, Japan
    • Saiseikai Kumamoto Hospital
  • Kurashiki, Japan
    • Kurashiki Central Hospital
  • Miyagi, Japan
    • Tohoku University Hospital
  • Miyazaki, Japan
    • University of Miyazaki Hospital
  • Miyazaki, Japan
    • Miyazaki Medical Association Hospital
  • Morioka, Japan
    • Iwate Medical University Hospital
  • Nagoya, Japan
    • Nagoya University Hospital
  • Nagoya, Japan
    • Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
  • Okayama, Japan
    • Okayama University Hospital
  • Okayama, Japan
    • The Sakakibara Heart Institute of Okayama
  • Osaka, Japan
    • National Cerebral and Cardiovascular Center
  • Osaka, Japan
    • Sakurabashi Watanabe Hospital
  • Saitama, Japan
    • Saitama Medical Center Jichi Medical University
  • Saitama, Japan
    • Saitama Medical University International Medical Center
  • Saitama, Japan
    • Japanese Red Cross Saitama Hospital
  • Shizuoka, Japan
    • Shizuoka General Hospital
  • Tokyo, Japan
    • Kyorin University Hospital
  • Tokyo, Japan
    • Juntendo University Hospital
  • Toyoake, Japan
    • Fujita Health University Hospital
  • Yamagata, Japan
    • Yamagata Prefectural Central Hospital
  • Yokohama, Japan
    • Saiseikai Yokohama tobu Hospital
  • Yokohama, Japan
    • St. Marianna University Yokohama City Seibu Hospital
  • Yufu, Japan
    • Oita University Hospital
• Korea, Republic of
  • Bucheon, Korea, Republic of
    • Sejong General Hospital
  • Daegu, Korea, Republic of
    • Keimyung University Dongsan Medical Center
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Kyung Hee University Medical Center
  • Seoul, Korea, Republic of
    • Severance Hospital
  • Seoul, Korea, Republic of
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Bundang Hospital
• Malaysia
  • Alor Setar, Malaysia
    • Hospital Sultanah Bahiyah
  • Kajang, Malaysia
    • Hospital Serdang
  • Kuala Lumpur, Malaysia
    • Institut Jantung Negara - National Heart Institute
  • Kuching, Malaysia
    • Sarawak Heart Centre
  • Sarawak
    • Kota Samarahan, Sarawak, Malaysia
      • Sarawak Heart Center
• Philippines
  • Makati, Philippines
    • Makati Medical Center
• Singapore
  • Singapore, Singapore
    • National University Hospital
  • Singapore, Singapore
    • Tan Tock Seng Hospital
  • Singapore, Singapore
    • Changi General Hospital
• Taiwan
  • Hsinchu, Taiwan
    • National Taiwan University Hospital Hsin Chu Branch
  • Kaohsiung City, Taiwan
    • Kaohsing Chang Gung Memorial Hospital
  • Taichung City, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Tainan, Taiwan
    • National Cheng Kung University Hospital
  • Taoyuan City, Taiwan, 333
    • Chang Gung Memorial Hospital LinKou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Device: aCRT ON; CRT device with AdaptivCRT enabled
Active Comparator: 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.	Device: aCRT OFF; CRT device with AdaptivCRT disabled

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in quality of life	QoL will be measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ); the overall summary score of the KCCQ will be analyzed. The responses are categorized under 3 subscales (symptom burden, physical limitation and quality of life) with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. The total KCCQ score represents the mean of the three subscale scores.	Baseline to 6 and 12 months post-randomization
Combined effects of height, QRS durations, and aCRT on clinical outcomes measured by the Clinical Composite Score	The combined effects of height, QRS duration and aCRT on the Clinical Composite Score will be assessed from the coefficients of a multivariable logistic regression model.	12 months post-randomization
Incidence of atrial fibrillation		12 months post-randomization
Occurrence of cardiovascular adverse events		12 months post-randomization
Degree of reverse cardiac remodeling		12 months post-randomization

Collaborators and Investigators

• Sponsor: Medtronic Bakken Research Center
• Collaborators: Medtronic; Medtronic Japan Co., Ltd.
• Investigators: Study Chair: Kazutaka Aonuma, MD, University of Tsukuba Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2020
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: November 18, 2019
• First Submitted That Met QC Criteria: November 26, 2019
• First Posted (Actual): November 27, 2019

Study Record Updates

• Last Update Posted (Actual): May 26, 2023
• Last Update Submitted That Met QC Criteria: May 25, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Heart Block; Heart Failure; Bundle-Branch Block
• Other Study ID Numbers: MDT18037

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No