Active and Completed Studies
Promising Results to Help Reshape the Treatment Pathway for Patients
The Carillon Therapy has been evaluated in four prior studies. The most recently completed study was a blinded, randomized, sham-controlled study which demonstrated that patients implanted with the Carillon Therapy and coupled with medical therapy were more likely to have reduced mitral regurgitation and experience a reduction in left ventricle size as compared to patients who were treated with medical therapy alone. The Carillon Therapy has been commercially available in Europe since 2011 with more than 1,500 patients receiving the Carillon Therapy worldwide.
We are currently enrolling patients in the U.S. pivotal EMPOWER Trial. The goal of this trial is to show the Carillon Therapy can be used earlier in a patient’s disease state and will ultimately lead to a new option to treat patients before their disease progresses and the damage becomes irreversible. Talk to your doctor to see if this trial is right for you.
For Further Information
JACC: Heart Failure
The REDUCE FMR Trial was the first double-blinded, randomized, sham-controlled trial of a percutaneous heart valve therapy. The REDUCE FMR Trial achieved its primary endpoint of reduction in regurgitant volume (RV) and demonstrated favorable left ventricular (LV) remodeling. A median 22% reduction in regurgitant volume was demonstrated, as assessed by a blinded, independent echo core lab. In addition, an improvement of almost 17ml versus the control group was shown in favorable left ventricular remodeling.
The results of The REDUCE FMR Trial are consistent with the prior Carillon Therapy studies.
Reduce FMR Results
Key eligibility criteria were similar to the prior trials of the Carillon Therapy including NYHA class II-IV, MR grade 2+ to 4+, LVEDD >55mm and an ejection fraction <50%, despite the use of stable guideline-directed medical therapy. Being double-blinded, the study was of the highest scientific rigor—patients and assessors were blinded throughout follow-up and the independent echo core lab not only was blinded to treatment and the timing of the images but also read the images in random order.
In total, 120 patients were randomly allocated to treatment (87) or the sham-control (33) arm at 31 sites in Europe, Australia, and New Zealand.
Echocardiographic evaluation was performed at the site prior to enrollment, and 35 patients (29.2%) were later judged by the independent echo core laboratory to have had MR 1+ at baseline. In 14 (16%) of those allocated to treatment, no device was implanted, due most commonly to coronary impingement (n=8) which resolved following device removal in all cases.
The average device implant time was 64.2 minutes and total procedure time averaged 102.7 minutes. Freedom from device-related major adverse events (MAE) was 98.9%, with no device embolizations, device fractures, cardiac perforations or intra-procedural ischemic events. There were two deaths within 30 days, both in implanted patients attributed to progressive cardio-renal deterioration. The incidence of MAE at 1 year was not statistically different between the treatment and control groups (16.1% in treatment group vs. 18.2% in control group).
The primary endpoint was met with a statistically significant reduction in mitral RV in the treatment group as compared to the control group (decrease of 7.1 mL/beat vs. an increase of 3.3 mL/beat, p=0.049). A secondary analysis of patients with more severe FMR (MR grade ≥3+) demonstrated a similar pattern of changes. Patients in the treatment group (n=15) experienced a reduction in mitral RV of 12.8 mL/beat whereas patients in the control group (n=8) experienced an increase of 0.6 mL/beat (p=0.14). In addition to improvements in RV, favorable reverse left ventricular (LV remodeling was demonstrated, with a significant reduction in LV volumes in patients receiving the device vs. the control group.
Patients in the treatment group also experienced a significant improvement in 6-minute walk distance at 12 months compared with their baseline (p=0.002), whereas patients allocated to the control group did not (p=0.29). Likewise, the treatment group had a significant improvement in NYHA class at 12 months compared with baseline (p=0.002) whereas patients allocated to the control group did not (p=0.75).
With REDUCE FMR, the Carillon Therapy became the first TMVr treatment to demonstrate significant favorable LV remodeling at 1 year and significant reduction in RV in a blinded, randomized, sham-controlled trial.
The TITAN II study achieved its endpoint and showed significant improvements in echo parameters and patient function.
TITAN II was a single-arm study designed to assess the safety and efficacy of an updated version of the Carillon Therapy. Inclusion and exclusion criteria were similar to those in TITAN. Patients had symptomatic congestive heart failure (NYHA class ≥2), MR grade 2+ to 4+, a dilated LV (LVEDD >55 mm) and an ejection fraction <40%. Quantitative assessments of MR were performed by an independent core echo laboratory, and MAE were reviewed by an independent data and safety monitoring board. In total, 36 patients were enrolled; 30 received a permanent implant.
TITAN II Results
European Journal of Heart Failure
The TITAN study met its endpoint and showed the Carillon Therapy can significantly and safely reduce FMR severity in heart failure patients, resulting in significantly favorable LV remodeling over 12 months and improved measures of clinical outcomes over 24 months.
The TITAN study was a prospective, non-randomized multi-center European study. The objective of the study was to determine if the Carillon Therapy could safely and effectively reduce FMR and yield a durable long-term clinical benefit. Follow-up included typical clinical and echo assessments through 1 year and implanted patients had an additional clinical follow-up assessment at 2 years. The study was rigorously conducted with oversight by independent parties including an independent echo core lab, clinical events committee, and a data and safety monitoring board. Key inclusion criteria included MR grade 2+ to 4+, NYHA Class II-IV and LVEF <40%.
Of the 53 patients enrolled in the study, 36 underwent permanent implant of the device. In 17 patients, the device was recaptured (due to transient coronary impingement (n=8) or <1 grade FMR reduction (n=9)). These non-implant patients were followed as a comparator group.
The first-in-human AMADEUS study met its endpoint and demonstrated successful deployment of the Carillon Therapy and a significant reduction in FMR.
AMADEUS was a single-arm, first-in-human study designed to evaluate the safety and feasibility of the Carillon Therapy. The study utilized several independent bodies to minimize bias and increase rigor, including a blinded independent echo core lab, clinical events committee, and data and safety monitoring board. Key inclusion criteria included moderate to severe FMR, NYHA class II-IV, LVEDD >55mm, and ejection fraction <40% receiving sustained stable and optimal HF medication regimen. The study enrolled 48 patients with the device successfully implanted in 30 patients. At six months, the degree of FMR reduction among five different quantitative echo measures ranged from 22-32%.
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NOTE: The Carillon Mitral Contour System has received CE Mark (0344) and is available for sale in Europe and other countries that recognize CE Mark.
CAUTION: Investigational Device. Limited by United States law to investigational use.