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Reducing the Burden of Parenteral Prostacyclin Therapy: The Totally Implantable Prostacyclin System


Sophia Airhart, MD
Sophia.Airhart@ahn.org

Amresh Raina, MD, FACC
Amresh.Raina@ahn.org
Allegheny General Hospital
Pittsburgh, PA, USA



As clinicians caring for patients with pulmonary arterial hypertension (PAH) we have all experienced the challenging situation in which a patient should ideally be treated with a parenteral prostacyclin for advanced symptoms but was not felt to be an appropriate candidate or declined to start prostacyclin therapy. The reasons for this are varied, including a history of non-compliance, an inability or unwillingness to maintain an access site and long-term infusion pump, or an unstable social situation.

In addition, in many patients, particularly young, active patients such as children and adolescents, there is sometimes a social stigma associated with carrying an infusion pump on a daily basis, and managing a parenteral prostacyclin can impact a patient's ability to do their daily activities such as playing sports, showering and swimming. Lastly, for those already on parental agents, there is also a significant daily burden of maintaining their infusion site, need to frequently mix drug, and risk of infection with intravenous agents. In essence, caring for their pump and infusion site becomes a portion of daily life for patients on parenteral prostacyclins.

This has led to greater interest in the use of alternative forms of prostacyclin therapy such as inhaled and now oral prostacyclin analogs. However, for patients with advanced symptoms, current guidelines still recommend use of parenteral agents.

So what if we could alleviate the burden of managing an infusion site, changing cassettes and mixing drug? Could this have a significant impact upon the patient's quality of life, satisfaction with prostacyclin therapy, and ultimately open up parenteral prostacyclin agents to a greater proportion of patients who actually warrant this therapy?

Recent results of a multicenter, prospective, single-arm, clinical trial (DelIVery for Pulmonary Arterial Hypertension) demonstrated the feasibility and clinical benefit of a novel implantable intravascular delivery system for continuous treprostinil which has potential to address this treatment gap and simplify the regimen for those patients already on IV treprostinil.

The implantable pump is placed in the abdomen and a catheter is connected to the infusion pump and then tunneled under the skin to the venous access site. Patients were typically discharged from the hospital 24 hours after implant and the pump was programmed to deliver a priming bolus followed by a continuous infusion of treprostinil from the pump reservoir. The pump refill process takes approximately 15 minutes and occurred when the drug volume in the pump reservoir was low at an interval dependent on the patient dose (up to 12 weeks with an average refill interval of 47 days). In this cohort of 60 implanted subjects at ten study sites, the drug delivery system maintained therapeutic drug levels as postimplantation plasma treprostinil levels were highly correlated with baseline levels.

In this preliminary study there were no catheter-related bloodstream infections or occlusions. Six-catheter related complications occurred in five patients over a mean duration of use of 367 days and included three catheter dislocations, one episode of mechanical catheter damage, one pneumothorax, and one episode of venous stasis. The complication rate of 0.27 per 1,000 patient-days with the implantable delivery device was markedly lower than the pre-defined criteria of 2.5 complications per 1000 days with external delivery devices.

Patients spent 75% less time managing their delivery system (average 0.6 hours per week), including time spent traveling to and from, and in, the PAH clinic compared with the external system they used prior to implantation (average 2.5 hours per week). The use of this system maintained NYHA functional class and 6MWD and was associated with a higher rate of patient satisfaction.

For patients requiring parenteral prostacyclins the new implantable pump may present a viable alternative to a traditional intravenous or subcutaneous method of administration. To the patient, the implantable device is simplified and more convenient; there is less room for user error with a more automated delivery system and no cassette mixing. The absence of a transcutaneous outlet resulted in a marked reduction in catheter-related complications. The majority of patients reported either no change or better quality of life, likely related to both convenience and being able to do more regular activities without concern for infusion site complications.

This novel drug delivery approach appears to improve the safety of IV prostanoid delivery and patient quality of life and has the potential to expand the availability of parenteral prostacyclins to a greater number of patients. ■

Disclosure Statement: The authors have no conflicts of interest to disclose.


References:

  1. Ryerson CJ, Nayar S, Swiston JR, et al. Pharmacotherapy in pulmonary arterial hypertension: a systematic review and meta-analysis. Respir Res 2010; 11:12
  2. Tapson VF, Gomberg-Maitland M. McLaughlin VV, et al Safety and efficacy of IV treprostinil for pulmonary arterial hypertension: a prospective, multicenter, open-label, 12-week trial. Chest. 2006;129:683-688
  3. Bourge RC, Waxman AB, Gomberg-Maitland M, et al. Treprostinil Administered to Treat Pulmonary Arterial Hypertension Using a Fully Implantable Programmable Intravascular Delivery System: Results of the DelIVery for PAH Trial. Chest. 2016 Jul;150(1):27-34.



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