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AdaptResponse Clinical Study (AdaptResponse Clinical Study)

AdaptResponse Clinical Study (AdaptResponse Clinical Study)

82

A total of 3797 individuals were enrolled and 82 individuals were enrolled in Japan. The mean age was 64.6+-11.1 years (mean+-standard deviation, the same below) in aCRT ON and 65.2+-11.0 years in aCRT OFF. The female ratio was 43.2% in aCRT ON and 43.5% in aCRT OFF. The percentage of subjects implanted with CRT-D was 95.1% in aCRT ON and 95.5% in aCRT OFF, which shows similar distribution between the two groups. In addition, there were no significant differences between the two groups at baseline for LVEF (Left Ventricular Ejection Fraction), presence of LBBB (Left Bundle Branch Block), QRS width, PR interval, NYHA Class II ratio, NYHA Class III/IV ratio, and non-ischemic cardiomyopathy ratio.

Participant flow The study utilizes an event-driven study design. Enrollment will end when approximately 3500 patients are randomized or there is reasonable certainty that the required number of events will be reached, as determined by the Data Monitoring Committee (DMC), whichever occurs first. The expected total study duration is approximately 5.5 years, representing approximately 3 years of enrollment and approximately 2.5 years of subject follow-up. Due to the occurrence rate of primary endpoints was lower than expected. A total of 3797 individuals were enrolled at 227 sites in 27 countries (82 individuals were enrolled in Japan) between August 2014 and January 2019. In total, 3617 participants (95.3%) were randomly assigned to aCRT ON (1810 subjects) or aCRT OFF (1807 subjects). In total, 180 enrolled subjects were not randomized. The most frequent reasons were not meeting the eligibility criteria (n=103) and not having a successful device implantation (n=56). In total, 620 subjects died and there were 784 subjects that exited the trial prematurely. Table 8 summarizes the reasons for premature exit. There were 16 premature exits reported as related to the COVID-19 pandemic. These are classified as Subject revoked consent (n=7), Subject refused reconsent (n=5) and Investigator exited subject (n=4, of which 3 classified as Subject lost to follow up). The DMC reviewed aggregate outcome data on April 23, 2021 to assess potential effects of the COVID-19 pandemic on AdaptResponse. The report presented data from the study approximately one year after the pandemic onset, and while there was an increase in study deviations over the course of 2020 and early 2021, the effects of COVID-19 upon mortality, study exits, or conditional disengagement appeared relatively minor. There were no data quality concerns or additional data collection requirements by the DMC.

All serious (SAEs), cardiovascular, device or procedure-related events from enrollment until subject exit were considered reportable. Pre-existing conditions (e.g., disease signs and/or symptoms) that, in the opinion of the responsible clinician, existed prior to study participation were not considered reportable, unless the condition recurred after the patient had recovered from the pre-existing condition, or the condition worsened in intensity or frequency during the study. Additionally, planned hospitalizations for a pre-existing condition without serious deterioration in health were not considered SAEs. n total, there have been 10947 Adverse Events (AEs) reported in 2615 subjects. Sponsor assessment was used to classify the seriousness and relatedness of the AEs. The most common reported AE is cardiac failure (N=1207, N=701 severe). The rate of AEs for a Serious Adverse Device Effect (SADE) was 16.9 % and it was comparable.

The primary endpoint of this study is the composite of all-cause death and any intervention for heart failure decompensation. A total of 1100 patients experiencing a primary endpoint will give 90% power to show a significant reduction of the incidence of the primary endpoint, assuming a true intent-to-treat hazard ratio of 0.82 for aCRT ON compared to aCRT OFF. As a result, the strategy of adaptive CRT compared with conventional CRT did not significantly reduce the incidence of all-cause mortality or HF events; therefore, the primary endpoint was not met. There are no significant differences between groups for secondary endpoints. Overall rates of all-cause mortality, HF events, AF were very low, and CRT response rates were very high. To understand the effects of synchronized LV pacing, a post-hoc analysis was performed. Patients with >= 85% synchronized LV pacing had a significantly (24%) lower mortality/HF rate.

This study is the largest randomized clinical trial of CRT in patients with HF, LBBB, and intact AV conduction. A strategy of adaptive CRT did not significantly reduce the combined endpoint of all-cause mortality or intervention for heart failure decompensation. Overall, patients in this trial experienced the lowest long-term mortality and the highest response rate across randomized trials of CRT. Overall, patients in this trial experienced the lowest long-term mortality and the highest response rate acros.

Aug. 31, 2023

No

Not Applicable.

https://jrct.mhlw.go.jp/latest-detail/jRCTs052180128

Kusano Kengo

National Cerebral and Cardiovascular Center

6-1 Kishibe-Shimmachi, Suita, Osaka, Japan

kusanokengo@gmail.com

Tokudome Chikako

National Cerebral and Cardiovascular Center

6-1 Kishibe-Shimmachi, Suita, Osaka, Japan

+81-6-6170-1070

tokudome.c@ncvc.go.jp

Complete

Nov. 10, 2014

Interventional

randomized controlled trial

single blind

active control

parallel assignment

treatment purpose

1 Subject is willing to sign and date the study Patient Informed Consent (PIC) Form.
2 Subject is indicated for a CRT device according to local guidelines.
3 Sinus Rhythm at time of enrollment.
4 Left Bundle Branch Block (LBBB) as documented on an ECG (within 30 days prior to enrollment). Criteria16 for complete LBBB must include:
-Intrinsic QRS duration >=140 ms (men) or >=130 ms (women), -QS or rS in leads V1 and V2
-Mid-QRS notching or slurring in >=2 of leads V1, V2, V5, V6, I, and aVL.
5 Intrinsic, normal AV conduction as documented on an ECG by a PR interval less than or equal to 200ms (within 30 days prior to enrollment).
6 Left ventricular ejection fraction less than or equal to 35% (documented within 180 days prior to enrollment).
7 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 Aldosterone Antagonist.

1 Subject is less than 18 years of age (or has not reached minimum age per local law).
2 Subject is not expected to remain available for at least 2 years of follow-up visits.
3 Subject has permanent atrial arrhythmias for which pharmacological therapy and/or cardioversion have been unsuccessful or have not been attempted.
4 Subject is, or previously has been, receiving cardiac resynchronization therapy.
5 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.
6 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.
7 Subject has a mechanical tricuspid heart valve or is scheduled to undergo valve repair or valve replacement during the course of the study.
8 Subject is post heart transplant (subjects on the heart transplant list for the first time are not excluded).
9 Subject has a limited life expectancy due to non-cardiac causes that would not allow completion of the study.
10 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).
11 Subject meets any exclusion criteria required by local law.

Both

Heart Failure

Treatment group (aCRT ON, with AdaptivCRT programmed to Adaptive Bi-V and LV)
Control group (aCRT OFF, with AdaptivCRT programmed to Nonadaptive CRT)

Heart Failure

To test the hypothesis that AdaptivCRT reduces the incidence of the combined endpoint of all-cause mortality and intervention for heart failure decompensation, compared to standard CRT therapy, in patients with a CRT indication, LBBB and normal AV conduction.

To test the hypothesis that aCRT ON reduces all-cause mortality compared to aCRT OFF etc.

+81-798-45-6066

Feb. 12, 2019

Australia/Canada/ Hungary/ Slovakia/Austria/Belgium/Denmark/Finland/ France/ Germany/ Italy/Netherlands/Norway/ Portugal/Poland/Spain/ Sweden/ Switzerland/United Kingdom/Iceland/ Russian Federation/ India/Korea/Mexico/ Saudi Arabia/Kuwait/ United Arab Emirates/Taiwan/United States