Implementing the EXPEDITE parenteral induction protocol: Rapid parenteral treprostinil titration and transition to oral treprostinil

Abstract

Treprostinil is a prostacyclin analogue that targets multiple cellular receptors to treat pulmonary arterial hypertension (PAH). In certain scenarios, patients may require aggressive treprostinil titration. Several studies have demonstrated that higher doses of treprostinil lead to greater clinical benefit. Data supports successful transitions from parenteral to oral treprostinil; however, administration routes, transition duration, and transition setting vary in the real‐world. The EXPEDITE clinical trial (NCT03497689) prospectively studied whether rapid parenteral treprostinil induction can be used to achieve high doses of oral treprostinil (total daily dose: ≥12 mg) in prostacyclin naïve PAH patients. Parenteral prostacyclin induction may be more appropriate for patients who need to reach therapeutic dosing more urgently than longer titration durations reported with conventional de novo oral treprostinil initiation. This summary provides strategies utilized in EXPEDITE. Parenteral treprostinil was initiated at 2 ng/kg/min intravenously or subcutaneously; clinicians determined the frequency and dose increment of up‐titration. Two distinct transition schedules from parenteral to oral treprostinil were employed: rapid cross‐titration in an inpatient setting (median: 2 days) or gradual cross‐titration in an outpatient setting (median: 5 days). Patient status was closely monitored after transition; oral treprostinil dose was titrated to clinical effect and tolerability. Factors considered when individualizing dosing strategies included parenteral and oral treprostinil target doses, nursing support, patient education, medication counseling and adverse events management. EXPEDITE demonstrated the time to a therapeutic dose of oral treprostinil is significantly shorter when utilizing a short‐term parenteral induction strategy and may be suitable for patients requiring aggressive titration of oral treprostinil.

Escalating Oral Treprostinil Dose With Intravenous Treprostinil Bridging Therapy

“…Rapid titration of IV treprostinil in a hospital setting followed by conversion to oral treprostinil was previously described by our group in 2015 [1] in a case of a patient unable to be placed on IV or subcutaneous treprostinil but in need of high-dose prostacyclin therapy. The EXPEDITE study [9] explored time-to-goal dosing through a prospective, multicenter, open-label study in evaluating whether a short-term course of IV treprostinil can assist patients in quickly achieving optimal goal dose of treprostinil, through various strategies, including rapid inpatient, moderately rapid outpatient, and gradual outpatient. The data from these studies are promising in terms of expediency and safety of rapid titration and attainment of goal dosing as opposed to de novo initiation of oral treprostinil therapy.…”