SESSION TITLE: Pulmonary Hypertension
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Tuesday, October 28, 2014 at 02:45 PM - 04:15 PM
PURPOSE: Utilization of systemic treprostinil infusion for advanced pulmonary artery hypertension (PAH) may be limited by external delivery system-related complications, including catheter-related bloodstream infection and subcutaneous infusion site pain. We postulated that a fully implantable intravascular delivery system would reduce the rate and severity of delivery-related adverse effects.
METHODS: The DelIVery for PAH clinical trial is a multi-center, prospective, single arm, non-randomized IDE study utilizing a fully implantable, programmable intravascular delivery system. Implanted pumps were refilled percutaneously with treprostinil at intervals dependent on the subject’s dose but less than 12 weeks. The primary analysis was a comparison of the rate of catheter-related complications using the newly developed implantable system compared to historical controls using external pump delivery systems.
RESULTS: Sixty implanted PAH subjects (80% female; mean age 53 years (range 24-74): mean baseline treprostinil dose 71.4 ng/kg/min (range 22-142) from 10 US clinical sites were followed for a mean of 367 days (range 87-701) after device implantation. Six catheter-related complications were observed, corresponding to a rate of 0.27 complications/1000 patient days (97.5% upper confidence bound: 0.59), which was significantly less than the upper reported rate of 2.5 complications/1000 patient days with external pump systems (p<0.0001). No bloodstream infections were associated with the implanted catheter. Mean time per week managing the delivery system decreased from 2.5 hours with the external system to 0.6 hours with the implantable system. The mean percentage increase for the 6-minute walk distance from baseline to 6 weeks post-implant was 0.2% (95% confidence interval: -4.9-5.2%). Mean plasma treprostinil levels with the external pump (10.9 mg/mL) and the implanted system (10.5 mg/mL) were similar. At 6 weeks and 6 months post implant, 100% of subjects rated the treatment overall as good, very good, or excellent.
CONCLUSIONS: The fully implantable programmable intravascular delivery system used in this study effectively delivered treprostinil in patients with PAH with a low rate of catheter-related complications and a high rate of patient satisfaction.
CLINICAL IMPLICATIONS: Treprostinil delivered by an implantable intravascular pump may reduce the amount of catheter related complications when compared to an external delivery system, and has similar outcomes for 6-minute walk distance for patients suffering from PAH.
DISCLOSURE: Robert Bourge: Consultant fee, speaker bureau, advisory committee, etc.: study consultant Aaron Waxman: Consultant fee, speaker bureau, advisory committee, etc.: study consultant Mardi Gomberg-Maitland: Consultant fee, speaker bureau, advisory committee, etc.: study consultant Jeff Cerkvenik: Employee: Medtronic Marty Morris: Employee: Medtronic Melissa Thalin: Employee: Medtronic Leigh Peterson: Employee: United Therapeutics Lewis Rubin: Consultant fee, speaker bureau, advisory committee, etc.: Medtronic consultant The following authors have nothing to disclose: Shelly Shapiro, James Tarver, Dianne Zwicke, Jeremy Feldman, Murali Chakinala, Robert Frantz, Fernando Torres
The purpose of this clinical trial is to evaluate the safety profile of the Model 10642 Implantable Intravascular Catheter portion of the PAH Implantable Vasodilator Therapy (PIVoT) system. This study will focus on the safety of delivery of RemodulinÂ® (treprostinil) Injection in the treatment of patients with PAH who meet the approved Remodulin Injection indication, using the approved formulation, and approved intravenous route of administration. The data generated by the study are intended to provide adequate safety information necessary to support Medtronic approval and FDA approval of a marketing application for the Model 10642 catheter and labeling updates for the SynchroMedÂ® II system, as well as an NDA-supplement from United Therapeutics to support updates to RemodulinÂ® Injection labeling.â