Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Bilton D

PROVIDER: S-EPMC9078215 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Bilton Diana D Pressler Tacjana T Fajac Isabelle I Clancy John Paul JP Sands Dorota D Minic Predrag P Cipolli Marco M Galeva Ivanka I Solé Amparo A Quittner Alexandra L AL Liu Keith K McGinnis John P JP Eagle Gina G Gupta Renu R Konstan Michael W MW

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 20190823 2

<h4>Background</h4>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.<h4>Methods</h4>Eligible patients with forced expiratory volume in 1 s (FEV<sub>1</sub>) ≥25% of predicted value at screening and CF with chronic P. aeruginosa infection were randomly assigned to receive 3 treatment cycles (28 day ...[more]

PMID: 31451351

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Project description:BackgroundMycobacterium abscessus is the second most common nontuberculous mycobacterium respiratory pathogen and shows in vitro resistance to nearly all oral antimicrobials. M abscessus treatment success is low in the presence of macrolide resistance.Research questionDoes treatment with amikacin liposome inhalation suspension (ALIS) improve culture conversion in patients with M abscessus pulmonary disease who are treatment naive or who have treatment-refractory disease?Study design and methodsIn an open-label protocol, patients were given ALIS (590 mg) added to background multidrug therapy for 12 months. The primary outcome was sputum culture conversion defined as three consecutive monthly sputum cultures showing negative results. The secondary end point included development of amikacin resistance.ResultsOf 33 patients (36 isolates) who started ALIS with a mean age of 64 years (range, 14-81 years), 24 patients (73%) were female, 10 patients (30%) had cystic fibrosis, and nine patients (27%) had cavitary disease. Three patients (9%) could not be evaluated for the microbiologic end point because of early withdrawal. All pretreatment isolates were amikacin susceptible and only six isolates (17%) were macrolide susceptible. Eleven patients (33%) were given parenteral antibiotics. Twelve patients (40%) received clofazimine with or without azithromycin as companion therapy. Fifteen patients (50%) with evaluable longitudinal microbiologic data demonstrated culture conversion, and 10 patients (67%) sustained conversion through month 12. Six of the 33 patients (18%) demonstrated mutational amikacin resistance. All were patients using clofazimine or clofazimine plus azithromycin as companion medication(s). Few serious adverse events occurred for ALIS users; however, reduction of dosing to three times weekly was common (52%).InterpretationIn a cohort of patients primarily with macrolide-resistant M abscessus, one-half of the patients using ALIS showed sputum culture conversion to negative findings. The emergence of mutational amikacin resistance was not uncommon and occurred with the use of clofazimine monotherapy.Trial registryClinicalTrials.gov; No.: NCT03038178; URL: www.Clinicaltrialsgov.

Project description:IntroductionThis study aimed to gain insight from patients with refractory Mycobacterium avium complex lung disease (MAC-LD) into strategies used to manage adverse events (AEs) associated with amikacin liposome inhalation suspension (ALIS).MethodsWe conducted semi-structured interviews with US patients with refractory MAC-LD prescribed ALIS in a real-world setting. Interview transcripts were analyzed and coded to identify patterns in participants' descriptions of their ALIS treatment experiences, including AEs and their disruptiveness, and AE mitigation strategies, including participants' ratings of strategies' effectiveness. Concept saturation was also assessed.ResultsTwenty participants (mean age 48.7 years; 80% women; mean ALIS duration 5.45 months) were interviewed. At the time of the interview, 15 participants (75%) had received ALIS for > 1 month and 13 (65%) were currently receiving ALIS. Participants described 44 unique AE mitigation strategies, which can be categorized into three groups: prepare for treatment; prevent increased emergence of AEs; and persist on treatment by mitigating AEs. Common strategies (reported by ≥ 50% of participants) included use of educational materials from the patient support program, localized management of throat irritation, and symptom management to reduce fatigue. Evidence of concept saturation was observed: no new strategies were identified in the last five interviews, which suggests the sample was robust enough to identify all mitigation strategies likely to be used by the broader patient population.ConclusionsThis real-world study identified a diverse set of potential AE mitigation strategies intended to help individual patients prepare for ALIS treatment, prevent the increased emergence of certain AEs, and mitigate the impact of AEs on treatment persistence. Developing a comprehensive accounting of the types of mitigation strategies in use among patients in real-world settings can inform future investigation of the effectiveness of such strategies, and support evidence-based recommendations for treatment management.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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