COPD associated pulmonary hypertension: A post hoc analysis of the PERFECT study
Abstract The PERFECT study, a randomized, controlled, double‐blind study of inhaled treprostinil in patients with COPD and associated pulmonary hypertension (PH‐COPD) was a negative trial that was terminated early. The reason(s) for the negative outcome remains uncertain. A post hoc analysis of data...
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| Format: | Article |
| Language: | English |
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Wiley
2024-10-01
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| Series: | Pulmonary Circulation |
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| Online Access: | https://doi.org/10.1002/pul2.12430 |
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| author | Steven D. Nathan Victoria Lacasse Heidi Bell Prakash Sista Michael Di Marino Todd Bull Victor Tapson Aaron Waxman |
| author_facet | Steven D. Nathan Victoria Lacasse Heidi Bell Prakash Sista Michael Di Marino Todd Bull Victor Tapson Aaron Waxman |
| author_sort | Steven D. Nathan |
| collection | DOAJ |
| description | Abstract The PERFECT study, a randomized, controlled, double‐blind study of inhaled treprostinil in patients with COPD and associated pulmonary hypertension (PH‐COPD) was a negative trial that was terminated early. The reason(s) for the negative outcome remains uncertain. A post hoc analysis of data from the PERFECT study was undertaken to identify adverse responders and possibly potential responders. The goal was also to provide insight into phenotypes for possible inclusion and exclusion in future PH‐COPD clinical trials. An adverse response on active treatment was seen in 36.4% (24/66) of the subjects compared to 27.6% (16/58) on placebo. There was no evidence to suggest that hyperinflation, bronchospasm, or occult heart failure played any role in the untoward outcomes of the study. The patients who died during the study all had baseline diffusing capacity for carbon monoxide ≤25% of predicted. Evidence of a potential response was seen in 10.6% (7/66) of the patients who received inhaled treprostinil. Patients who had evidence of a treatment response had a baseline mean pulmonary artery pressure of ≥40 mmHg and a forced expiratory volume in the first second of ≥40%. Change in N‐terminal prohormone of brain natriuretic peptide did not predict clinical response. This post hoc analysis provides information that may potentially enable improved selection of patients for future therapeutic trials in PH‐COPD. These analyses are post hoc, observational, and exploratory. The thresholds defining the spectrum of responders are preliminary and may require further refinement and validation in future studies. |
| format | Article |
| id | doaj-art-feced9c966ee4e358d344b769b1f4bf6 |
| institution | Kabale University |
| issn | 2045-8940 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pulmonary Circulation |
| spelling | doaj-art-feced9c966ee4e358d344b769b1f4bf62024-12-27T05:54:34ZengWileyPulmonary Circulation2045-89402024-10-01144n/an/a10.1002/pul2.12430COPD associated pulmonary hypertension: A post hoc analysis of the PERFECT studySteven D. Nathan0Victoria Lacasse1Heidi Bell2Prakash Sista3Michael Di Marino4Todd Bull5Victor Tapson6Aaron Waxman7Inova Fairfax Hospital Falls Church Virginia USAUnited Therapeutics Silver Spring Maryland USAUnited Therapeutics Chapel Hill North Carolina USAUnited Therapeutics Silver Spring Maryland USAUnited Therapeutics Silver Spring Maryland USAPulmonary Sciences and Critical Care Medicine and Cardiology University of Colorado Denver Colorado USACedars Sinai Medical Center Los Angeles California USABrigham and Women's Hospital Boston Massachusetts USAAbstract The PERFECT study, a randomized, controlled, double‐blind study of inhaled treprostinil in patients with COPD and associated pulmonary hypertension (PH‐COPD) was a negative trial that was terminated early. The reason(s) for the negative outcome remains uncertain. A post hoc analysis of data from the PERFECT study was undertaken to identify adverse responders and possibly potential responders. The goal was also to provide insight into phenotypes for possible inclusion and exclusion in future PH‐COPD clinical trials. An adverse response on active treatment was seen in 36.4% (24/66) of the subjects compared to 27.6% (16/58) on placebo. There was no evidence to suggest that hyperinflation, bronchospasm, or occult heart failure played any role in the untoward outcomes of the study. The patients who died during the study all had baseline diffusing capacity for carbon monoxide ≤25% of predicted. Evidence of a potential response was seen in 10.6% (7/66) of the patients who received inhaled treprostinil. Patients who had evidence of a treatment response had a baseline mean pulmonary artery pressure of ≥40 mmHg and a forced expiratory volume in the first second of ≥40%. Change in N‐terminal prohormone of brain natriuretic peptide did not predict clinical response. This post hoc analysis provides information that may potentially enable improved selection of patients for future therapeutic trials in PH‐COPD. These analyses are post hoc, observational, and exploratory. The thresholds defining the spectrum of responders are preliminary and may require further refinement and validation in future studies.https://doi.org/10.1002/pul2.12430double‐blind methodchronic obstructivehypertensionpulmonarypulmonary diseasetreprostinil |
| spellingShingle | Steven D. Nathan Victoria Lacasse Heidi Bell Prakash Sista Michael Di Marino Todd Bull Victor Tapson Aaron Waxman COPD associated pulmonary hypertension: A post hoc analysis of the PERFECT study Pulmonary Circulation double‐blind method chronic obstructive hypertension pulmonary pulmonary disease treprostinil |
| title | COPD associated pulmonary hypertension: A post hoc analysis of the PERFECT study |
| title_full | COPD associated pulmonary hypertension: A post hoc analysis of the PERFECT study |
| title_fullStr | COPD associated pulmonary hypertension: A post hoc analysis of the PERFECT study |
| title_full_unstemmed | COPD associated pulmonary hypertension: A post hoc analysis of the PERFECT study |
| title_short | COPD associated pulmonary hypertension: A post hoc analysis of the PERFECT study |
| title_sort | copd associated pulmonary hypertension a post hoc analysis of the perfect study |
| topic | double‐blind method chronic obstructive hypertension pulmonary pulmonary disease treprostinil |
| url | https://doi.org/10.1002/pul2.12430 |
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