Quality of life, safety and efficacy profile of thermostable flolan in pulmonary arterial hypertension

Steeve Provencher, Patrap Paruchuru, Andrea Spezzi, Brian Waterhouse, Mardi Gomberg-Maitland, pH12 Flolan reformulation study group, Steeve Provencher, Patrap Paruchuru, Andrea Spezzi, Brian Waterhouse, Mardi Gomberg-Maitland, Steeve Provencher, Patrap Paruchuru, Andrea Spezzi, Brian Waterhouse, Mardi Gomberg-Maitland, pH12 Flolan reformulation study group, Steeve Provencher, Patrap Paruchuru, Andrea Spezzi, Brian Waterhouse, Mardi Gomberg-Maitland

Abstract

Background: Flolan (epoprostenol sodium) is most commonly prescribed to patients with severe pulmonary arterial hypertension (PAH) owing to the requirement that the drug be delivered by continuous intravenous infusion and the reconstituted solution may only be administered up to 24 hours when it is maintained between a temperature of 2°C and 8°C. The aim of this single-arm, open label study was to describe the effects of the new thermostable formulation of Flolan on health-related quality of life (HRQoL) and ease of administration in subjects switching from the currently marketed Flolan to the reformulated product.

Methods: Following a 4-week run-in period and after 4 weeks of treatment with the reformulated product, patients completed the SF-36 HRQoL questionnaire and a study-specific questionnaire evaluating ease of administration, along with World Health Organization (WHO) functional class, six-minute walked distance (6MWD) and N-terminal-pro B-type natriuretic peptide (NT-proBNP) assessment.

Results: 16 participants completed the study. The SF-36 scores remained unchanged from baseline to Week 4. Conversely, there were small improvements for the majority of the study-specific questionnaire items and 14 (88%) subjects preferred the reformulated product to the currently marketed Flolan. There was no significant change in the dose of reformulated product, 6MWD, Borg dyspnoea index, WHO functional class and mean NT-proBNP levels. No significant changes in haemodynamic parameters were seen from baseline to 2 hours post transition in a subset of patients undergoing catheterization.

Conclusion: The reformulated product was not associated with significant improvement in HRQoL compared with the currently marketed Flolan as measured by the SF-36. However, most subjects preferred the reformulated product to the currently marketed Flolan. Moreover, the 2 formulations of Flolan had similar safety and efficacy profiles.

Trial registration: ClinicalTrials.gov NCT01462565.

Conflict of interest statement

Competing Interests: SP is a research scholar of the Fonds de Recherche en Santé du Québec and as received speaker fees from Actelion, consultant fees from Actelion, Bayer, Merck and Pfizer, and research grant from Actelion, Bayer and Glaxo Smith Kline. PP, AS and BW are employed by Glaxo Smith Kline. MGM has no conflict of interest to declare. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Study flow chart.
Fig 1. Study flow chart.
One patient was excluded because of a catheter site infection which developed during screening period (before the baseline visit).
Fig 2. Individual SF-36 domain scores at…
Fig 2. Individual SF-36 domain scores at baseline and after 4 weeks of treatment with the reformulated product.
The box plots are schematic box and whisker plots such that the whisker above represents the largest observed value that falls within for the upper fence (3rd quartile + 1.5 * IQR) and the whisker below represents the smallest observed value that falls within the lower fence (1st quartile—1.5 * IQR). IQR = inner quartile range calculated as 3rd quartile value minus 1st quartile value. PF: physical functioning; RP: role physical; RE: role emotional; VT: vitality; MH: mental health; SF: social functioning; BP: bodily pain; GH: general health; PHC: mean physical health component score; MHC: mean mental health component score.
Fig 3. Individual 6 Minute Walk distance…
Fig 3. Individual 6 Minute Walk distance at the time of screening, at baseline and after 4 weeks of treatment with the reformulated product.
Fig 4. Mean N-terminal-pro B-type natriuretic peptide…
Fig 4. Mean N-terminal-pro B-type natriuretic peptide levels at baseline and after 4 weeks of treatment with the reformulated product.
The box plots are schematic box and whisker plots such that the whisker above represents the largest observed value that falls within for the upper fence (3rd quartile + 1.5 * IQR) and the whisker below represents the smallest observed value that falls within the lower fence (1st quartile—1.5 * IQR). IQR = inner quartile range calculated as 3rd quartile value minus 1st quartile value.

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