Amikacin liposome inhalation suspension for chronic Pseudomonas aeruginosa infection in cystic fibrosis

Autor: Diana Bilton, Tacjana Pressler, Isabelle Fajac, John Paul Clancy, Dorota Sands, Predrag Minic, Marco Cipolli, Ivanka Galeva, Amparo Solé, Alexandra L. Quittner, Keith Liu, John P. McGinnis, Gina Eagle, Renu Gupta, Michael W. Konstan, Sabine Renner, Christiane Knoop, Anne Malfroot, Lieven Dupont, Kristine Desager, Frans De Baets, Miroslava Bosheva, Vania Nedkova, Ivan Galabov, Andreas Freitag, Nancy Morrison, Pearce Wilcox, Tanja Pressler, Yves Martinet, Raphael Chiron, Stephan Dominique, Philippe Reix, Anne Prevotat, Isabelle Sermet, Isabelle Durieu, Rainald Fischer, Rudolf Huber, Doris Staab, Uwe Mellies, Wolfgang Sextro, Tobias Welte, Heinrike Wilkens, Urte Sommerwerk, Burkhard Bewig, Ilias Inglezos, Stavros-Eleftherios Doudounakis, Olga Bede, Ferenc Gönczi, Rita Újhelyi, Edward McKone, Paul McNally, Vincenzina Lucidi, Mario La Rosa, Laura Minicucci, Rita Padoan, Giovanna Pisi, Rolando Gagliardini, Carla Colombo, Inez Bronsveld, Ewa Sapiejka, Henryk Mazurek, Grażyna Górnicka, Iwona Stelmach, Halina Batura-Gabryel, Marta Rachel, Jaroslava Orosova, Branko Takac, Anna Feketova, Carmen Martinez, Gloria Garcia Hernandez, Jose Ramon Villa-Asensi, Silvia Gartner, Amparo Sole, Anders Lindblad, Martin Ledson, Joanna Whitehouse, Alan Smyth, Ian Ketchell, Timothy Lee, Gordon MacGregor
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Cystic Fibrosis
Gastroenterology
Cystic fibrosis
0302 clinical medicine
Surveys and Questionnaires
Tobramycin
education.field_of_study
Inhalation
Symptom Flare Up
3. Good health
Anti-Bacterial Agents
Respiratory Function Tests
Hospitalization
medicine.anatomical_structure
Treatment Outcome
Amikacin
Pseudomonas aeruginosa
Female
medicine.symptom
Symptom Assessment
medicine.drug
Pulmonary and Respiratory Medicine
Adult
medicine.medical_specialty
Population
Article
03 medical and health sciences
Internal medicine
Administration
Inhalation
medicine
Humans
Pseudomonas Infections
education
Adverse effect
Lung
Dose-Response Relationship
Drug
business.industry
Sputum
medicine.disease
respiratory tract diseases
030104 developmental biology
030228 respiratory system
Pediatrics
Perinatology and Child Health
Liposomes
business
Zdroj: J Cyst Fibros
ISSN: 1873-5010
Popis: Background Shortcomings of inhaled antibiotic treatments for Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) include poor drug penetration, inactivation by sputum, poor efficiency due to protective biofilm, and short residence in the lung. Methods Eligible patients with forced expiratory volume in 1 s (FEV1) ≥25% of predicted value at screening and CF with chronic P. aeruginosa infection were randomly assigned to receive 3 treatment cycles (28 days on, 28 days off) of amikacin liposome inhalation suspension (ALIS, 590 mg QD) or tobramycin inhalation solution (TIS, 300 mg BID). The primary endpoint was noninferiority of ALIS vs TIS in change from baseline to day 168 in FEV1 (per-protocol population). Secondary endpoints included change in respiratory symptoms by Cystic Fibrosis Questionnaire-Revised (CFQ-R). Results The study was conducted February 2012 to September 2013. ALIS was noninferior to TIS (95% CI, −4.95 to 2.34) for relative change in FEV1 (L) from baseline. The mean increases in CFQ-R score from baseline on the Respiratory Symptoms scale suggested clinically meaningful improvement in both arms at the end of treatment in cycle 1 and in the ALIS arm at the end of treatment in cycles 2 and 3; however, the changes were not statistically significant between the 2 treatment arms. Treatment-emergent adverse events (TEAEs) were reported in most patients (ALIS, 84.5%; TIS, 78.8%). Serious TEAEs occurred in 17.6% and 19.9% of patients, respectively; most were hospitalisations for infective pulmonary exacerbation of CF. Conclusions Cyclical dosing of once-daily ALIS was noninferior to cyclical twice-daily TIS in improving lung function. ClinicalTrials.gov Identifier: NCT01315678
Databáze: OpenAIRE
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