Oral Treprostinil for the Treatment of Pulmonary Arterial Hypertension in Patients Receiving Background Endothelin Receptor Antagonist and Phosphodiesterase Type 5 Inhibitor Therapy (The FREEDOM-C2 Study)

Tapson, Victor F.; Jing, Zhi‐Cheng; Xu, Kai‐Feng; Pan, Lei; Feldman, Jeremy; Kiely, David G.; Kotlyar, Eugene; McSwain, C. Shane; Laliberte, Kevin; Arneson, Carl; Rubin, Lewis J.

doi:10.1378/chest.12-2875

Cited by 268 publications

(240 citation statements)

References 17 publications

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“…Possible reasons for not reaching the predefined composite end point of our study include the presence of stable background PAH therapy at baseline and the relatively short duration of the trial; a longer trial may have allowed titration of the study drug to higher doses, which might have had greater efficacy, as discussed in the main publication on the FREEDOM-C2 study. 27 In addition, a predefined combined end point was reached by 16.8% of patients in a large multicenter study investigating the inhalation of iloprost, 34 highlighting the complexity of reaching numerous strict end points in multicenter trials.…”

Section: Discussionmentioning

confidence: 99%

“…The dose threshold was the mean dose of oral treprostinil received by patients at week 16 (3.1 ± 1.9 mg twice daily). 27 …”

Section: Study Objectivesmentioning

confidence: 99%

“…We therefore assessed Ang-2 and sP-selectin levels in patients with PAH participating in the FREEDOM-C2 study of oral treprostinil. 27 We hypothesized that Ang-2 and sP-selectin levels are associated with the treatment response when oral treprostinil is administered in combination with other PAH medications and that they may therefore have an impact on clinical decision-making and disease monitoring.…”

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confidence: 99%

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Relevance of Angiopoietin‐2 and Soluble P‐Selectin Levels in Patients with Pulmonary Arterial Hypertension Receiving Combination Therapy with Oral Treprostinil: A FREEDOM‐C2 Biomarker Substudy

et al. 2016

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Studies have suggested roles for angiopoietin-2 (Ang-2) and soluble P-selectin (sP-selectin) as biomarkers of disease severity and treatment response in pulmonary arterial hypertension (PAH), but additional data are required for validation. We evaluated these biomarkers using data from FREEDOM-C2, in which patients with PAH receiving stable monotherapy or combination therapy were randomized to receive additional treatment with oral treprostinil (up-titrated from 0.25 mg twice daily) or placebo for 16 weeks. Biomarker analysis was optional in FREEDOM-C2. We measured plasma Ang-2 and sP-selectin levels at baseline and at week 16, and we assessed their association with predefined outcomes (6-minute walk distance [6MWD] change from baseline >40 m, 6MWD >380 m, functional class I/II, and/or N-terminal pro-brain natriuretic peptide [NT-proBNP] <1,800 pg/mL at week 16) using Spearman correlation, receiver operating characteristics, and logistic regression. Biomarker data were available for 83 of 157 and 95 of 153 patients in the oral treprostinil and placebo groups, respectively. In the oral treprostinil group, baseline Ang-2 levels correlated with week 16 NT-proBNP levels (P < 0.0001). Baseline Ang-2 ≥12 ng/mL was associated with a reduced likelihood of having NT-proBNP <1,800 pg/mL at week 16 (multivariate odds ratio: 0.08; 95% confidence interval: 0.02-0.32). However, Ang-2 showed no significant association with the other assessed outcomes, and sP-selectin was not associated or correlated with any of the outcomes. These data suggest that Ang-2 and sP-selectin are not associated with response to oral treprostinil in patients already receiving stable PAH therapy. Trial registration: Clinicaltrials.gov identifier NCT00887978.

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Section: Discussionmentioning

confidence: 99%

“…The dose threshold was the mean dose of oral treprostinil received by patients at week 16 (3.1 ± 1.9 mg twice daily). 27 …”

Section: Study Objectivesmentioning

confidence: 99%

mentioning

confidence: 99%

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Relevance of Angiopoietin‐2 and Soluble P‐Selectin Levels in Patients with Pulmonary Arterial Hypertension Receiving Combination Therapy with Oral Treprostinil: A FREEDOM‐C2 Biomarker Substudy

et al. 2016

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“…55,56 A comparison between results with oral treprostinil in combination with other background PAH therapy in the FREEDOM-C and FREEDOM-C2 studies did not demonstrate a significant improvement in exercise capacity. 57,58 Iloprost is a prostacyclin analogue that is beneficial to patients with idiopathic PAH when administered via inhalation. A recent study showed that inhaled iloprost has acute beneficial effects on pulmonary hemodynamics and resulted in both acute and sustained symptomatic improvement in patients with portopulmonary hypertension.…”

Section: Prostanoidsmentioning

confidence: 99%

Untitled

Coşarderelioğlu

Coşar

Gürakar

et al. 2016

Exp Clin Transplant

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Portopulmonary hypertension is one of the main pulmonary conditions affecting patients with liver disease and/or portal hypertension. Other conditions include hepatopulmonary syndrome and hepatic hydrothorax. Portopulmonary hypertension is caused by pulmonary vasoconstriction and increased pulmonary vascular resistance. It develops as a result of portal hypertension with or without liver disease and is associated with a higher morbidity and mortality. However, portopulmonary hypertension is usually asymptomatic; the most common symptoms are dyspnea, fatigue, and peripheral edema. All liver transplant candidates should be screened for potential portopulmonary hypertension because its coexistence can affect survival rates after transplant. All patients with cirrhosis who present with dyspnea should also be screened. Transthoracic echocardiography is a noni nvasive, useful method for screening, but right heart-sided catheterization remains the criterion standard for diagnosis. Portopulmonary hypertension carries a poor prognosis without liver transplant, and its severe form is considered to be a contraindication for liver transplant. Treating patients with pulmonary arterial hypertension-specific therapies before liver transplant for moderate and severe portopulmonary hypertension appears to be beneficial.

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“…[117][118][119] Oral treprostinil was shown to effective as initial monotherapy treatment in adult PAH 120 , but not as add-on therapy. 121 Studies using oral treprostinil in children are ongoing.…”

Section: Calcium Channel Blockersmentioning

confidence: 99%

Pulmonary hypertension in children

2012

Arch Dis Child

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Oral Treprostinil for the Treatment of Pulmonary Arterial Hypertension in Patients Receiving Background Endothelin Receptor Antagonist and Phosphodiesterase Type 5 Inhibitor Therapy (The FREEDOM-C2 Study)

Abstract: ClinicalTrials.gov; No.: NCT00887978; URL: www.clinicaltrials.gov.

Cited by 268 publications

References 17 publications

Relevance of Angiopoietin‐2 and Soluble P‐Selectin Levels in Patients with Pulmonary Arterial Hypertension Receiving Combination Therapy with Oral Treprostinil: A FREEDOM‐C2 Biomarker Substudy

Relevance of Angiopoietin‐2 and Soluble P‐Selectin Levels in Patients with Pulmonary Arterial Hypertension Receiving Combination Therapy with Oral Treprostinil: A FREEDOM‐C2 Biomarker Substudy

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Pulmonary hypertension in children

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