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Intravenous treprostinil infusion via a fully implantable pump for pulmonary arterial hypertension

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Abstract

Objectives

Parenteral prostanoids infused via external pumps are well-established pulmonary arterial hypertension (PAH) treatments. However, local side-effects and systemic infections restrict their use. The purpose of this study was to investigate the safety of a fully implantable treprostinil infusion pump (LENUS Pro®) in patients with PAH.

Methods

Thirty patients with PAH undergoing pump implantation (with stable PAH therapy for ≥3 weeks pre-implantation) were included in this prospective, multicenter, observational study (NCT01979822). Primary endpoints were predefined adverse events (AEs) during implantation, in-hospital and/or during 6-month follow-up. Refill-related AEs were a secondary endpoint.

Results

Twenty-nine patients completed 6-month follow-up (one underwent lung transplantation). During implantation, one pneumothorax (not requiring drainage) occurred. Four patients had an in-hospital AE (including one catheter revision). During 6-month follow-up, AEs were most frequent at the first refill (10); the most common AE was seroma around the pump. No infections occurred. One pump required replacement because of a defective septum caused by use of a non-approved refill needle (associated with extravasation). Apart from the extravasation, no refill-related AEs were recorded. Post hoc efficacy analyses showed significant improvements in functional class [number in functional class I/II/III/IV: 0/5/21/2 (baseline) versus 3/8/17/0 (6 months); p = 0.012] and 6-min walk distance (mean ± standard deviation: 407 ± 122 m versus 445 ± 127 m; n = 17; p = 0.014).

Conclusions

This study supports use of a fully implantable treprostinil infusion pump in patients with PAH requiring parenteral prostanoids. Refills should be performed by specialized healthcare professionals at patients’ homes or at experienced centers using approved equipment.

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Acknowledgements

We would like to thank all participating pulmonary hypertension centers, the surgeons who implanted the pump, and all dedicated support staff for taking care of the patients’ LENUS Pro® refills. In addition, we would like to thank Dr. Anne Obst (University of Greifswald) for statistical assistance. This study was supported by the University of Greifswald, Germany. Editorial assistance was provided by Dr. Claire Mulligan (Beacon Medical Communications Ltd, Brighton, UK) funded by OMT GmbH.

Author information

Author notes

  1. Ralf Ewert and Manuel J. Richter contributed equally to this work and are both considered first authors.

Authors and Affiliations

  1. Department of Internal Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany

    Ralf Ewert & Christian Warnke

  2. Department of Pneumology, Kerckhoff Heart and Thoracic Center, Bad Nauheim, Germany

    Manuel J. Richter & Hossein-Ardeschir Ghofrani

  3. Department of Internal Medicine, Member of the German Center for Lung Research (DZL), Justus Liebig University Giessen, Universities of Giessen and Marburg Lung Center, Klinikstrasse 33, 35392, Giessen, Germany

    Manuel J. Richter & Hossein-Ardeschir Ghofrani

  4. Department of Cardiology and Angiology, Public Hospital Elisabethinen Linz, Linz, Austria

    Regina Steringer-Mascherbauer

  5. Academic Teaching Center, Linz, Austria

    Regina Steringer-Mascherbauer

  6. Centre for Pulmonary Hypertension, Thoraxklinik at the University Hospital Heidelberg, Heidelberg, Germany

    Ekkehard Grünig

  7. Division of Pneumology, Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany

    Tobias J. Lange

  8. Department of Cardiology, DRK Kliniken Berlin, Berlin, Germany

    Christian F. Opitz

  9. Department of Medicine, Imperial College London, London, UK

    Hossein-Ardeschir Ghofrani

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  1. Ralf Ewert
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Corresponding author

Correspondence to Hossein-Ardeschir Ghofrani.

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Conflict of interest

Dr. Ewert has received speaker fees and fees for participation in advisory boards from United Therapeutics/OMT, Pfizer, GlaxoSmithKline (GSK), Actelion, Novartis, Bayer HealthCare, and Encysive/Pfizer, and grants from Actelion and Boehringer Ingelheim. Dr. Steringer-Mascherbauer has received unrestricted grants from Actelion, GSK, AOP and Bayer, and fees for participation in advisory boards from Actelion, MSD and United Therapeutics. Dr. Grünig has received speaker fees from Bayer, Actelion, Pfizer, and GSK; fees for participation in advisory boards from Bayer, Pfizer, GSK, and Actelion; and industry-sponsored grants from Bayer HealthCare and Actelion. Dr. Lange has received speaker fees, honoraria for consultations, and research funding from Actelion, AOP Orphan Pharmaceuticals, Bayer, GSK, Novartis, Pfizer, and United Therapeutics. Dr. Opitz’s institution has received speaker fees and honoraria for consultations from Actelion, Bayer, GSK and Pfizer. Dr. Warnke has received speaker fees from United Therapeutics/OMT. Dr. Richter has received support from United Therapeutics and Bayer Pharma AG, and speaker fees from Actelion, Mundipharma, Roche, and United Therapeutics/OMT. Dr. Ghofrani has received consultancy fees from Bayer, Actelion, Pfizer, Merck, GSK, and Novartis; fees for participation in advisory boards from Bayer, Pfizer, GSK, Actelion, and Takeda; lecture fees from Bayer HealthCare, GSK, Actelion, and Encysive/Pfizer; industry-sponsored grants from Bayer HealthCare, Aires, Encysive/Pfizer, and Novartis; and sponsored grants from the German Research Foundation, Excellence Cluster Cardiopulmonary Research, and the German Ministry for Education and Research.

Ethical standards

The study was approved by the leading ethics committee of the University of Greifswald (BB 109/12, Amendment 109/12a), and local ethics committees of the recruiting centers if applicable; the study was therefore performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All patients gave written informed consent prior to their inclusion in the study.

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Ewert, R., Richter, M.J., Steringer-Mascherbauer, R. et al. Intravenous treprostinil infusion via a fully implantable pump for pulmonary arterial hypertension. Clin Res Cardiol 106, 776–783 (2017). https://doi.org/10.1007/s00392-017-1114-1

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  • DOI: https://doi.org/10.1007/s00392-017-1114-1

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