Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease

被引：420

作者：

Waxman, Aaron ^{[1
]}

Restrepo-Jaramillo, Ricardo ^{[2
]}

Thenappan, Thenappan ^{[4
]}

Ravichandran, Ashwin ^{[5
]}

Engel, Peter ^{[6
]}

Bajwa, Abubakr ^{[3
]}

Allen, Roblee ^{[7
]}

Feldman, Jeremy ^{[9
]}

Argula, Rahul ^{[10
]}

Smith, Peter ^{[11
]}

Rollins, Kristan ^{[11
]}

Deng, Chunqin ^{[11
]}

Peterson, Leigh ^{[11
]}

Bell, Heidi ^{[11
]}

Tapson, Victor ^{[8
]}

Nathan, Steven D. ^{[12
]}

机构：

[1] Brigham & Womens Hosp, Boston, MA 02115 USA

[2] Univ S Florida, Tampa, FL 33620 USA

[3] St Vincents Lung Sleep & Crit Care Specialists, Jacksonville, FL USA

[4] Univ Minnesota, Minneapolis, MN USA

[5] St Vincent Med Grp, Indianapolis, IN USA

[6] Christ Hosp, Carl & Edyth Lindner Res Ctr, Cincinnati, OH 45219 USA

[7] Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA

[8] Cedars Sinai, Los Angeles, CA USA

[9] Arizona Pulm Specialists, Phoenix, AZ USA

[10] Med Univ South Carolina, Charleston, SC 29425 USA

[11] United Therapeut Corp, Silver Spring, MD USA

[12] Inova Fairfax Hosp, Falls Church, VA USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2021年 / 384卷 / 04期

关键词：

ARTERIAL-HYPERTENSION; GAS-EXCHANGE; ILOPROST; VALIDATION; THERAPY;

D O I：

10.1056/NEJMoa2008470

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND No therapies are currently approved for the treatment of pulmonary hypertension in patients with interstitial lung disease. The safety and efficacy of inhaled treprostinil for patients with this condition are unclear. METHODS We enrolled patients with interstitial lung disease and pulmonary hypertension (documented by right heart catheterization) in a multicenter, randomized, double-blind, placebo-controlled, 16-week trial. Patients were assigned in a 1:1 ratio to receive inhaled treprostinil, administered by means of an ultrasonic, pulsed-delivery nebulizer in up to 12 breaths (total, 72 mu g) four times daily, or placebo. The primary efficacy end point was the difference between the two groups in the change in peak 6-minute walk distance from baseline to week 16. Secondary end points included the change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level at week 16 and the time to clinical worsening. RESULTS A total of 326 patients underwent randomization, with 163 assigned to inhaled treprostinil and 163 to placebo. Baseline characteristics were similar in the two groups. At week 16, the least-squares mean difference between the treprostinil group and the placebo group in the change from baseline in the 6-minute walk distance was 31.12 m (95% confidence interval [CI], 16.85 to 45.39; P<0.001). There was a reduction of 15% in NT-proBNP levels from baseline with inhaled treprostinil as compared with an increase of 46% with placebo (treatment ratio, 0.58; 95% CI, 0.47 to 0.72; P<0.001). 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; 95% CI, 0.40 to 0.92; P=0.04 by the log-rank test). The most frequently reported adverse events were cough, headache, dyspnea, dizziness, nausea, fatigue, and diarrhea. CONCLUSIONS 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.

引用

页码：325 / 334

页数：10

共 16 条

[1] Inhaled Treprostinil in Group-3 Pulmonary Hypertension [J].