Long-term results of the DelIVery for Pulmonary Arterial Hypertension trial

Mardi Gomberg-Maitland, Robert C Bourge, Shelley M Shapiro, James H Tarver 3rd, Dianne L Zwicke, Jeremy P Feldman, Murali M Chakinala, Robert P Frantz, Fernando Torres, Remzi Bag, Jeffrey A Murphy, Amy A Lautenbach, Marty Morris, Leigh Peterson, Aaron B Waxman, Mardi Gomberg-Maitland, Robert C Bourge, Shelley M Shapiro, James H Tarver 3rd, Dianne L Zwicke, Jeremy P Feldman, Murali M Chakinala, Robert P Frantz, Fernando Torres, Remzi Bag, Jeffrey A Murphy, Amy A Lautenbach, Marty Morris, Leigh Peterson, Aaron B Waxman

Abstract

Background: The DelIVery for Pulmonary Arterial Hypertension clinical trial was a multi-center, prospective, single arm, Investigational Device Exemption study utilizing a fully implantable, programmable intravascular delivery system consisting of a pump and a catheter for intravenous treprostinil. The study met its primary endpoint and demonstrated that the intravascular delivery system significantly reduced catheter related complications at 22,000 subject-days of follow-up compared with a predefined objective performance criterion. Here we summarize the results obtained during a 6.4-year follow-up period.

Methods: Throughout study follow-up, participants had clinic visits and medication refills at least every 12 weeks (dependent on the subjects' dose). All adverse events and intravascular delivery system complications were evaluated and recorded.

Results: Sixty pulmonary arterial hypertension subjects were followed post device implantation for approximately 282 patient-years (range 87 days to 6.4 years). Of the 60 subjects, 14 died (1 related to intravascular delivery system pump failure), 2 withdrew after lung transplants, and 2 withdrew due to pump pocket infection. No catheter-related bloodstream infections, catheter thrombosis or occlusions, or catheter kinks occurred through 282 patient-years. Two participants had adverse events of abdominal pain, rash, due to subcutaneous treprostinil "leaks" after one catheter puncture and one catheter laceration during pump refill and replacement, respectively. Eight pump failure events occurred: seven pump motor stalls and one early replacement (faulty battery).

Conclusion: Delivery of treprostinil with an intravascular delivery system is a safe alternative to an external delivery system, while providing enhanced life experiences. To preserve the risk-benefit ratio, treatment at specialized pulmonary arterial hypertension centers is recommended until training is disseminated at other sites.

Keywords: internal device; prostacyclin; pulmonary arterial hypertension; treprostinil.

© The Author(s) 2019.

Figures

Fig. 1.
Fig. 1.
CONSORT flow diagram.
Fig. 2.
Fig. 2.
Kaplan–Meier survivorship plot with 95% confidence limit error bars. Five-year estimate from implant to death 76.4% (95% CI 63.3–85.3%).
Fig. 3.
Fig. 3.
Scatter plot of years post-implant (x-axis) vs. estimated pump motor turns (y-axis), with pump motor stalls identified with solid circles.
Fig. 4.
Fig. 4.
Kaplan–Meier survivorship plots with 95% confidence limit error bars. (a) Five-year estimate from implant to catheter failure 94.3% (95% CI 83.1–98.2%). (b) Five-year estimate from implant to pump failure 87.7% (95% CI 72.9–94.7%). (c) Five-year estimate from implant to pump replacement or explanted without replacement 74.9% (95% CI 60.0–85.0%). (d) Five-year estimate from implant to system modification 69.8% (95% CI 54.9–80.7%).
Fig. 4.
Fig. 4.
Kaplan–Meier survivorship plots with 95% confidence limit error bars. (a) Five-year estimate from implant to catheter failure 94.3% (95% CI 83.1–98.2%). (b) Five-year estimate from implant to pump failure 87.7% (95% CI 72.9–94.7%). (c) Five-year estimate from implant to pump replacement or explanted without replacement 74.9% (95% CI 60.0–85.0%). (d) Five-year estimate from implant to system modification 69.8% (95% CI 54.9–80.7%).
Fig. 5.
Fig. 5.
Adverse event proportion over time for the five most common therapy related adverse events.
Fig. 6.
Fig. 6.
Implantable system for remodulin expected accuracy ratio for a 40-mL refill volume. The shaded area represents the DelIVery for PAH clinical trial accuracy data (95/95% tolerance interval of the exponential data model).

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Source: PubMed

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