Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease.

Administration, Inhalation Adult Aged Aged, 80 and over Antihypertensive Agents / adverse effects Double-Blind Method Epoprostenol / adverse effects Exercise Tolerance / drug effects Female Humans Hypertension, Pulmonary / drug therapy Least-Squares Analysis Lung Diseases, Interstitial / complications Male Middle Aged Quality of Life Walk Test

Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
28 01 2021
Historique:
pubmed: 14 1 2021
medline: 11 2 2021
entrez: 13 1 2021
Statut: ppublish

Résumé

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. 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 μg) 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. 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. 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. (Funded by United Therapeutics; INCREASE ClinicalTrials.gov number, NCT02630316.).

Sections du résumé

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 μg) 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. (Funded by United Therapeutics; INCREASE ClinicalTrials.gov number, NCT02630316.).

Identifiants

DOI: 10.1056/NEJMoa2008470 PMID: 33440084
pubmed: 33440084
doi: 10.1056/NEJMoa2008470
doi:

Substances chimiques

Antihypertensive Agents 0
Epoprostenol DCR9Z582X0
treprostinil RUM6K67ESG

Banques de données

ClinicalTrials.gov
['NCT02630316']

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

325-334

Commentaires et corrections

Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2021 Massachusetts Medical Society.

Auteurs

Aaron Waxman (A)

From Brigham and Women's Hospital, Boston (A.W.); the University of South Florida, Tampa (R.R.-J.), and St. Vincent's Lung, Sleep, and Critical Care Specialists, Jacksonville (A.B.) - both in FL; the University of Minnesota, Minneapolis (T.T.); St. Vincent Medical Group, Indianapolis (A.R.); the Carl and Edyth Lindner Research Center at the Christ Hospital, Cincinnati (P.E.); University of California Davis Medical Center, Sacramento (R. Allen), and Cedars-Sinai, Los Angeles (V.T.); Arizona Pulmonary Specialists, Phoenix (J.F.); the Medical University of South Carolina, Charleston (R. Argula); United Therapeutics Corporation, Silver Spring, MD (P.S., K.R., C.D., L.P., H.B.); and Inova Fairfax Hospital, Falls Church, VA (S.D.N.).

Ricardo Restrepo-Jaramillo (R)

From Brigham and Women's Hospital, Boston (A.W.); the University of South Florida, Tampa (R.R.-J.), and St. Vincent's Lung, Sleep, and Critical Care Specialists, Jacksonville (A.B.) - both in FL; the University of Minnesota, Minneapolis (T.T.); St. Vincent Medical Group, Indianapolis (A.R.); the Carl and Edyth Lindner Research Center at the Christ Hospital, Cincinnati (P.E.); University of California Davis Medical Center, Sacramento (R. Allen), and Cedars-Sinai, Los Angeles (V.T.); Arizona Pulmonary Specialists, Phoenix (J.F.); the Medical University of South Carolina, Charleston (R. Argula); United Therapeutics Corporation, Silver Spring, MD (P.S., K.R., C.D., L.P., H.B.); and Inova Fairfax Hospital, Falls Church, VA (S.D.N.).

Thenappan Thenappan (T)

From Brigham and Women's Hospital, Boston (A.W.); the University of South Florida, Tampa (R.R.-J.), and St. Vincent's Lung, Sleep, and Critical Care Specialists, Jacksonville (A.B.) - both in FL; the University of Minnesota, Minneapolis (T.T.); St. Vincent Medical Group, Indianapolis (A.R.); the Carl and Edyth Lindner Research Center at the Christ Hospital, Cincinnati (P.E.); University of California Davis Medical Center, Sacramento (R. Allen), and Cedars-Sinai, Los Angeles (V.T.); Arizona Pulmonary Specialists, Phoenix (J.F.); the Medical University of South Carolina, Charleston (R. Argula); United Therapeutics Corporation, Silver Spring, MD (P.S., K.R., C.D., L.P., H.B.); and Inova Fairfax Hospital, Falls Church, VA (S.D.N.).

Ashwin Ravichandran (A)

From Brigham and Women's Hospital, Boston (A.W.); the University of South Florida, Tampa (R.R.-J.), and St. Vincent's Lung, Sleep, and Critical Care Specialists, Jacksonville (A.B.) - both in FL; the University of Minnesota, Minneapolis (T.T.); St. Vincent Medical Group, Indianapolis (A.R.); the Carl and Edyth Lindner Research Center at the Christ Hospital, Cincinnati (P.E.); University of California Davis Medical Center, Sacramento (R. Allen), and Cedars-Sinai, Los Angeles (V.T.); Arizona Pulmonary Specialists, Phoenix (J.F.); the Medical University of South Carolina, Charleston (R. Argula); United Therapeutics Corporation, Silver Spring, MD (P.S., K.R., C.D., L.P., H.B.); and Inova Fairfax Hospital, Falls Church, VA (S.D.N.).

Peter Engel (P)

From Brigham and Women's Hospital, Boston (A.W.); the University of South Florida, Tampa (R.R.-J.), and St. Vincent's Lung, Sleep, and Critical Care Specialists, Jacksonville (A.B.) - both in FL; the University of Minnesota, Minneapolis (T.T.); St. Vincent Medical Group, Indianapolis (A.R.); the Carl and Edyth Lindner Research Center at the Christ Hospital, Cincinnati (P.E.); University of California Davis Medical Center, Sacramento (R. Allen), and Cedars-Sinai, Los Angeles (V.T.); Arizona Pulmonary Specialists, Phoenix (J.F.); the Medical University of South Carolina, Charleston (R. Argula); United Therapeutics Corporation, Silver Spring, MD (P.S., K.R., C.D., L.P., H.B.); and Inova Fairfax Hospital, Falls Church, VA (S.D.N.).

Abubakr Bajwa (A)

From Brigham and Women's Hospital, Boston (A.W.); the University of South Florida, Tampa (R.R.-J.), and St. Vincent's Lung, Sleep, and Critical Care Specialists, Jacksonville (A.B.) - both in FL; the University of Minnesota, Minneapolis (T.T.); St. Vincent Medical Group, Indianapolis (A.R.); the Carl and Edyth Lindner Research Center at the Christ Hospital, Cincinnati (P.E.); University of California Davis Medical Center, Sacramento (R. Allen), and Cedars-Sinai, Los Angeles (V.T.); Arizona Pulmonary Specialists, Phoenix (J.F.); the Medical University of South Carolina, Charleston (R. Argula); United Therapeutics Corporation, Silver Spring, MD (P.S., K.R., C.D., L.P., H.B.); and Inova Fairfax Hospital, Falls Church, VA (S.D.N.).

Roblee Allen (R)

From Brigham and Women's Hospital, Boston (A.W.); the University of South Florida, Tampa (R.R.-J.), and St. Vincent's Lung, Sleep, and Critical Care Specialists, Jacksonville (A.B.) - both in FL; the University of Minnesota, Minneapolis (T.T.); St. Vincent Medical Group, Indianapolis (A.R.); the Carl and Edyth Lindner Research Center at the Christ Hospital, Cincinnati (P.E.); University of California Davis Medical Center, Sacramento (R. Allen), and Cedars-Sinai, Los Angeles (V.T.); Arizona Pulmonary Specialists, Phoenix (J.F.); the Medical University of South Carolina, Charleston (R. Argula); United Therapeutics Corporation, Silver Spring, MD (P.S., K.R., C.D., L.P., H.B.); and Inova Fairfax Hospital, Falls Church, VA (S.D.N.).

Jeremy Feldman (J)

From Brigham and Women's Hospital, Boston (A.W.); the University of South Florida, Tampa (R.R.-J.), and St. Vincent's Lung, Sleep, and Critical Care Specialists, Jacksonville (A.B.) - both in FL; the University of Minnesota, Minneapolis (T.T.); St. Vincent Medical Group, Indianapolis (A.R.); the Carl and Edyth Lindner Research Center at the Christ Hospital, Cincinnati (P.E.); University of California Davis Medical Center, Sacramento (R. Allen), and Cedars-Sinai, Los Angeles (V.T.); Arizona Pulmonary Specialists, Phoenix (J.F.); the Medical University of South Carolina, Charleston (R. Argula); United Therapeutics Corporation, Silver Spring, MD (P.S., K.R., C.D., L.P., H.B.); and Inova Fairfax Hospital, Falls Church, VA (S.D.N.).

Rahul Argula (R)

From Brigham and Women's Hospital, Boston (A.W.); the University of South Florida, Tampa (R.R.-J.), and St. Vincent's Lung, Sleep, and Critical Care Specialists, Jacksonville (A.B.) - both in FL; the University of Minnesota, Minneapolis (T.T.); St. Vincent Medical Group, Indianapolis (A.R.); the Carl and Edyth Lindner Research Center at the Christ Hospital, Cincinnati (P.E.); University of California Davis Medical Center, Sacramento (R. Allen), and Cedars-Sinai, Los Angeles (V.T.); Arizona Pulmonary Specialists, Phoenix (J.F.); the Medical University of South Carolina, Charleston (R. Argula); United Therapeutics Corporation, Silver Spring, MD (P.S., K.R., C.D., L.P., H.B.); and Inova Fairfax Hospital, Falls Church, VA (S.D.N.).

Peter Smith (P)

From Brigham and Women's Hospital, Boston (A.W.); the University of South Florida, Tampa (R.R.-J.), and St. Vincent's Lung, Sleep, and Critical Care Specialists, Jacksonville (A.B.) - both in FL; the University of Minnesota, Minneapolis (T.T.); St. Vincent Medical Group, Indianapolis (A.R.); the Carl and Edyth Lindner Research Center at the Christ Hospital, Cincinnati (P.E.); University of California Davis Medical Center, Sacramento (R. Allen), and Cedars-Sinai, Los Angeles (V.T.); Arizona Pulmonary Specialists, Phoenix (J.F.); the Medical University of South Carolina, Charleston (R. Argula); United Therapeutics Corporation, Silver Spring, MD (P.S., K.R., C.D., L.P., H.B.); and Inova Fairfax Hospital, Falls Church, VA (S.D.N.).

Kristan Rollins (K)

From Brigham and Women's Hospital, Boston (A.W.); the University of South Florida, Tampa (R.R.-J.), and St. Vincent's Lung, Sleep, and Critical Care Specialists, Jacksonville (A.B.) - both in FL; the University of Minnesota, Minneapolis (T.T.); St. Vincent Medical Group, Indianapolis (A.R.); the Carl and Edyth Lindner Research Center at the Christ Hospital, Cincinnati (P.E.); University of California Davis Medical Center, Sacramento (R. Allen), and Cedars-Sinai, Los Angeles (V.T.); Arizona Pulmonary Specialists, Phoenix (J.F.); the Medical University of South Carolina, Charleston (R. Argula); United Therapeutics Corporation, Silver Spring, MD (P.S., K.R., C.D., L.P., H.B.); and Inova Fairfax Hospital, Falls Church, VA (S.D.N.).

Chunqin Deng (C)

From Brigham and Women's Hospital, Boston (A.W.); the University of South Florida, Tampa (R.R.-J.), and St. Vincent's Lung, Sleep, and Critical Care Specialists, Jacksonville (A.B.) - both in FL; the University of Minnesota, Minneapolis (T.T.); St. Vincent Medical Group, Indianapolis (A.R.); the Carl and Edyth Lindner Research Center at the Christ Hospital, Cincinnati (P.E.); University of California Davis Medical Center, Sacramento (R. Allen), and Cedars-Sinai, Los Angeles (V.T.); Arizona Pulmonary Specialists, Phoenix (J.F.); the Medical University of South Carolina, Charleston (R. Argula); United Therapeutics Corporation, Silver Spring, MD (P.S., K.R., C.D., L.P., H.B.); and Inova Fairfax Hospital, Falls Church, VA (S.D.N.).

Leigh Peterson (L)

From Brigham and Women's Hospital, Boston (A.W.); the University of South Florida, Tampa (R.R.-J.), and St. Vincent's Lung, Sleep, and Critical Care Specialists, Jacksonville (A.B.) - both in FL; the University of Minnesota, Minneapolis (T.T.); St. Vincent Medical Group, Indianapolis (A.R.); the Carl and Edyth Lindner Research Center at the Christ Hospital, Cincinnati (P.E.); University of California Davis Medical Center, Sacramento (R. Allen), and Cedars-Sinai, Los Angeles (V.T.); Arizona Pulmonary Specialists, Phoenix (J.F.); the Medical University of South Carolina, Charleston (R. Argula); United Therapeutics Corporation, Silver Spring, MD (P.S., K.R., C.D., L.P., H.B.); and Inova Fairfax Hospital, Falls Church, VA (S.D.N.).

Heidi Bell (H)

From Brigham and Women's Hospital, Boston (A.W.); the University of South Florida, Tampa (R.R.-J.), and St. Vincent's Lung, Sleep, and Critical Care Specialists, Jacksonville (A.B.) - both in FL; the University of Minnesota, Minneapolis (T.T.); St. Vincent Medical Group, Indianapolis (A.R.); the Carl and Edyth Lindner Research Center at the Christ Hospital, Cincinnati (P.E.); University of California Davis Medical Center, Sacramento (R. Allen), and Cedars-Sinai, Los Angeles (V.T.); Arizona Pulmonary Specialists, Phoenix (J.F.); the Medical University of South Carolina, Charleston (R. Argula); United Therapeutics Corporation, Silver Spring, MD (P.S., K.R., C.D., L.P., H.B.); and Inova Fairfax Hospital, Falls Church, VA (S.D.N.).

Victor Tapson (V)

From Brigham and Women's Hospital, Boston (A.W.); the University of South Florida, Tampa (R.R.-J.), and St. Vincent's Lung, Sleep, and Critical Care Specialists, Jacksonville (A.B.) - both in FL; the University of Minnesota, Minneapolis (T.T.); St. Vincent Medical Group, Indianapolis (A.R.); the Carl and Edyth Lindner Research Center at the Christ Hospital, Cincinnati (P.E.); University of California Davis Medical Center, Sacramento (R. Allen), and Cedars-Sinai, Los Angeles (V.T.); Arizona Pulmonary Specialists, Phoenix (J.F.); the Medical University of South Carolina, Charleston (R. Argula); United Therapeutics Corporation, Silver Spring, MD (P.S., K.R., C.D., L.P., H.B.); and Inova Fairfax Hospital, Falls Church, VA (S.D.N.).

Steven D Nathan (SD)

From Brigham and Women's Hospital, Boston (A.W.); the University of South Florida, Tampa (R.R.-J.), and St. Vincent's Lung, Sleep, and Critical Care Specialists, Jacksonville (A.B.) - both in FL; the University of Minnesota, Minneapolis (T.T.); St. Vincent Medical Group, Indianapolis (A.R.); the Carl and Edyth Lindner Research Center at the Christ Hospital, Cincinnati (P.E.); University of California Davis Medical Center, Sacramento (R. Allen), and Cedars-Sinai, Los Angeles (V.T.); Arizona Pulmonary Specialists, Phoenix (J.F.); the Medical University of South Carolina, Charleston (R. Argula); United Therapeutics Corporation, Silver Spring, MD (P.S., K.R., C.D., L.P., H.B.); and Inova Fairfax Hospital, Falls Church, VA (S.D.N.).

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Administration par inhalation › Inhaled Treprostinil in Pulmonary Hypertension...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Inhaled Treprostinil in Pulmonary Hypertension...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Inhaled Treprostinil in Pulmonary Hypertension...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Sujet âgé de 80 ans ou plus › Inhaled Treprostinil in Pulmonary Hypertension...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents cardiovasculaires › Antihypertenseurs › Inhaled Treprostinil in Pulmonary Hypertension...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Méthode en double aveugle › Inhaled Treprostinil in Pulmonary Hypertension...
questionsmedicales.fr › Facteurs biologiques › Médiateurs de l'inflammation › Autacoïdes › Éicosanoïdes › Prostaglandines › Prostaglandines I › Prostacycline › Inhaled Treprostinil in Pulmonary Hypertension...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système locomoteur › Tolérance à l'effort › Inhaled Treprostinil in Pulmonary Hypertension...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Inhaled Treprostinil in Pulmonary Hypertension...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Hypertension artérielle › Hypertension pulmonaire › Inhaled Treprostinil in Pulmonary Hypertension...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Analyse de régression › Méthode des moindres carrés › Inhaled Treprostinil in Pulmonary Hypertension...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Maladies pulmonaires › Pneumopathies interstitielles › Inhaled Treprostinil in Pulmonary Hypertension...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Inhaled Treprostinil in Pulmonary Hypertension...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Mesures épidémiologiques › Démographie › État de santé › Qualité de vie › Inhaled Treprostinil in Pulmonary Hypertension...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Techniques de diagnostic cardiovasculaire › Tests de la fonction cardiaque › Test de marche › Inhaled Treprostinil in Pulmonary Hypertension...