Inhaled Treprostinil effective in Pulmonary Hypertension Due to ILD: NEJM study
Pulmonary hypertension secondary to interstitial lung disease (PH-ILD) is commonly encountered in clinical practice and linked to significant morbidity and mortality. Recent trial findings suggest that Inhaled treprostinil was well tolerated and significantly improved pulmonary outcomes over 16 weeks in patients with pulmonary hypertension associated with interstitial lung disease. The research has been published in The New England Journal Of Medicine on January 13, 2020.
Treprostinil (Tyvaso) is a prostacyclin analogue. It directs vasodilation of pulmonary and systemic arterial vascular beds and inhibits platelet aggregation. It is specifically indicated to increase walk distance in patients with WHO Group I pulmonary arterial hypertension and NYHA Class III symptoms. Phase 2 trial on treprostinil showed promising results, however, the safety and efficacy of inhaled treprostinil are unclear and need further investigation. Therefore, researchers conducted a phase 3 trial to evaluate the safety and efficacy of treprostinil in patients with pulmonary hypertension associated with interstitial lung disease.
INCREASE trial was a phase III, multicenter, randomized, double-blind, placebo-controlled, 16-week trial in 326 patients with PH-ILD. Researchers randomly assigned patients in either inhaled treprostinil (n=163) administered by an ultrasonic, pulsed-delivery nebulizer in up to 12 breaths (total, 72 μg) four times daily or placebo (n=163). The major outcome assessed was the difference between the two groups in the change in peak 6-minute walk distance from the baseline to week 16. They also assessed the change in N-terminal pro–B-type natriuretic peptide (NT-proBNP) level at week 16 and the time to clinical worsening.
Key findings of the study were:
♦ Researchers noted similar baseline characteristics between the groups.
♦ At week 16, they noted that the patients in the inhaled treprostinil group had a placebo-corrected median improvement from baseline in 6-minute walk distance of 21 m. Using a different statistical approach, mixed-model repeated measurement, they noted treatment with inhaled treprostinil increased 6-minute walk distance by 31.12m.
♦ They noted that the Inhaled treprostinil resulted in a 15% reduction in NT-proBNP when compared with placebo which increased it by 46%.
♦ They observe that clinical worsening occurred in 37 patients (22.7%) in the treprostinil group as compared with 54 patients (33.1%) in the placebo group (hazard ratio, 0.61).
♦ The most frequently reported adverse events were cough, headache, dyspnea, dizziness, nausea, fatigue, and diarrhea.
The authors concluded, "In patients with pulmonary hypertension due to interstitial lung disease, inhaled treprostinil improved exercise capacity from baseline, assessed with the use of a 6-minute walk test, as compared with placebo".
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