Post-FDA Approval Study With a Continuous Flow LVAD
Objectives. A post-approval (PA) study for destination therapy (DT) was required by the Food and Drug Administration (FDA) to determine whether results with the HeartMate (HM) II (Thoratec, Pleasanton, California) left ventricular assist device (LVAD) in a commercial setting were comparable to results during the DT multicenter pivotal clinical trial.
Background. New device technology developed in the clinical research setting requires validation in a real-world setting.
Methods. The PA study was a prospective evaluation of the first 247 HM II patients identified pre-operatively as eligible for DT in the national INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) registry. Patients were enrolled from January to September 2010 at 61 U.S. centers and followed for 2 years. A historical comparison group included patients (n = 133 at 34 centers) enrolled in the primary data cohort in the DT pivotal trial (TR). Survival rates and adverse events for the PA group were obtained from the INTERMACS registry.
Results. Baseline characteristics were similar for PA versus TR. Forty-five percent of PA patients were in INTERMACS profiles 1 to 2 and 28% were in profile 3. Adverse events in the PA group were similar or lower than those in the TR group, including improvements in device-related infection (0.22 vs. 0.47) and post-operative bleeding requiring surgery (0.09 vs. 0.23) events per patient-year. Kaplan-Meier survival at 2 years was 62% (PA group) versus 58% (TR group). PA group survival at 1 and 2 years was 82 ± 5% and 69 ± 6% for INTERMACS profiles 4 to 7 (n = 63) versus 72 ± 3% and 60 ± 4% for profiles 1 to 3 (n = 184). The median length of stay after surgery was reduced by 6 days in the PA group versus the TR group.
Conclusions. Results in a commercial patient care setting for the DT population supported the original pivotal clinical trial findings regarding the efficacy and risk profile of the HM II LVAD. Survival was best in patients who were not inotrope-dependent (INTERMACS profiles 4 to 7).
Continuous-flow (CF) left ventricular assist devices (CF-LVADs) have successfully replaced the previous generation of pulsatile flow devices for patients with advanced heart failure. Moreover, observational studies following initial approval for the bridge-to-transplant (BTT) indication by the Food and Drug Administration (FDA) have demonstrated excellent outcomes with the HeartMate (HM) II (Thoratec, Pleasanton, California) when used by clinicians in the commercial (i.e., outside of the clinical trial) setting. Of note, success for the BTT indication is generally defined as "alive on device or transplanted by 180 days," and is by definition accomplished in patients who are candidates for cardiac transplantation (i.e., relatively young and without major comorbidities).
More recently, following a pivotal multicenter trial conducted from 2005 to 2010, which had a primary endpoint of survival at 2 years on the original device and without disabling stroke, the HM II was also approved for destination therapy (DT). DT candidates are not eligible for cardiac transplantation, are typically older, and frequently have a higher burden of comorbidities. Management of this patient cohort is more complex, and results obtained in a strictly regulated clinical trial setting may not be achievable in clinical commercial use. Accordingly, and to fulfill requirements by the FDA for a post-approval (PA) study, we compared outcomes of the first HeartMate II DT patients in commercial use to DT patients in the pivotal trial (TR). We hypothesized that LVAD patients who underwent implantation for DT in commercial use would have comparable outcomes to the clinical trial.
Abstract and Introduction
Abstract
Objectives. A post-approval (PA) study for destination therapy (DT) was required by the Food and Drug Administration (FDA) to determine whether results with the HeartMate (HM) II (Thoratec, Pleasanton, California) left ventricular assist device (LVAD) in a commercial setting were comparable to results during the DT multicenter pivotal clinical trial.
Background. New device technology developed in the clinical research setting requires validation in a real-world setting.
Methods. The PA study was a prospective evaluation of the first 247 HM II patients identified pre-operatively as eligible for DT in the national INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) registry. Patients were enrolled from January to September 2010 at 61 U.S. centers and followed for 2 years. A historical comparison group included patients (n = 133 at 34 centers) enrolled in the primary data cohort in the DT pivotal trial (TR). Survival rates and adverse events for the PA group were obtained from the INTERMACS registry.
Results. Baseline characteristics were similar for PA versus TR. Forty-five percent of PA patients were in INTERMACS profiles 1 to 2 and 28% were in profile 3. Adverse events in the PA group were similar or lower than those in the TR group, including improvements in device-related infection (0.22 vs. 0.47) and post-operative bleeding requiring surgery (0.09 vs. 0.23) events per patient-year. Kaplan-Meier survival at 2 years was 62% (PA group) versus 58% (TR group). PA group survival at 1 and 2 years was 82 ± 5% and 69 ± 6% for INTERMACS profiles 4 to 7 (n = 63) versus 72 ± 3% and 60 ± 4% for profiles 1 to 3 (n = 184). The median length of stay after surgery was reduced by 6 days in the PA group versus the TR group.
Conclusions. Results in a commercial patient care setting for the DT population supported the original pivotal clinical trial findings regarding the efficacy and risk profile of the HM II LVAD. Survival was best in patients who were not inotrope-dependent (INTERMACS profiles 4 to 7).
Introduction
Continuous-flow (CF) left ventricular assist devices (CF-LVADs) have successfully replaced the previous generation of pulsatile flow devices for patients with advanced heart failure. Moreover, observational studies following initial approval for the bridge-to-transplant (BTT) indication by the Food and Drug Administration (FDA) have demonstrated excellent outcomes with the HeartMate (HM) II (Thoratec, Pleasanton, California) when used by clinicians in the commercial (i.e., outside of the clinical trial) setting. Of note, success for the BTT indication is generally defined as "alive on device or transplanted by 180 days," and is by definition accomplished in patients who are candidates for cardiac transplantation (i.e., relatively young and without major comorbidities).
More recently, following a pivotal multicenter trial conducted from 2005 to 2010, which had a primary endpoint of survival at 2 years on the original device and without disabling stroke, the HM II was also approved for destination therapy (DT). DT candidates are not eligible for cardiac transplantation, are typically older, and frequently have a higher burden of comorbidities. Management of this patient cohort is more complex, and results obtained in a strictly regulated clinical trial setting may not be achievable in clinical commercial use. Accordingly, and to fulfill requirements by the FDA for a post-approval (PA) study, we compared outcomes of the first HeartMate II DT patients in commercial use to DT patients in the pivotal trial (TR). We hypothesized that LVAD patients who underwent implantation for DT in commercial use would have comparable outcomes to the clinical trial.
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