eFlow® Vibrating Membrane Nebulizer for the Treatment of Cystic Fibrosis

PICHON-RIVIERE, A.; AUGUSTOVSKI, F. A.; GARCIA MARTI, S.; GLUJOVSKY, D.; ALCARAZ, A.; LOPEZ, A.; BARDACH, A.; CIAPPONI, A

Documento de Evaluación de Tecnologías Sanitarias

IECS

Año: 2012 p. 1 - 30

1668-2793

Cystic fibrosis is an autosomal recessive disorder present in approximately 1/2,500 Caucasian live-borns. Its symptoms may include persistent pulmonary infections constituting the most common cause of morbidity and mortality in these patients. Several treatments are used to treat it; many of them are inhaled.This type of nebulizer may substantially change the amount of inhaled drug since the inhaled particle size may vary according to the type of device.In cystic fibrosis patients, the use of eFlow® - a vibrating membrane nebulizer - is proposed because it would increase the amount of drug deposited in the lungs (when compared with conventional nebulizers), thus improving the results and increasing the patient´s adherence.TechnologyNebulizers are devices that turn liquid into spray drops. The success of spray therapy depends on the fact that the proper amount of drug is deposited in the bronchi. eFlow® has a micro-perforated vibrating membrane that would offer proper drop size, resulting in tiny and high-density particles which may reduce the nebulization time with good access to the target tissue and low oropharyngeal deposit.PurposeTo assess the evidence available on the safety, efficacy and other issues related to the coverage polices of the use of eFlow® (vibrating membrane nebulizer) for the treatment of cystic fibrosis patients.MethodsA bibliographic search was carried out on the main databases: DARE, NHS EED, on Internet general search engines, in health technology evaluation agencies and health sponsors. Priority was given to the inclusion of systematic reviews; controlled, randomized clinical trials (RCTs); health technology assessments and economic evaluations; clinical practice guidelines and coverage policies of other health systems.ResultsTwo open-label, crossed-arms RCTs and 3 quasi-experimental studies, one clinical practice guideline and one health technology assessment report were found. Also, data from coverage policies from health sponsors are also reported.One open-label, crossed-arm RCT where 25 cystic fibrosis and chronic Pseudomonae aeruginosa patients were randomized to tobramycin, administered by eFlow® versus LCplus® nebulizer, was published in 2009. The treatment was 15-day-long in each arm, with a 7-day free interval between both arms. Nebulization times were significantly shorter with eFlow® than with LC Plus? both on Day 1 (-10.5 min, 95% CI -12.6 to -8.3, p<0.01) and on Day 15 (-7.7 min, 95% CI -9.0 to -6.5, p<0.01). No significant differences were found neither in tobramycin concentrations or peak concentration in sputum, or in adverse events.Another open-label, crossed-arm RCT where 13 subjects ((7 with cystic fibrosis and 6 healthy) were randomized to tobramycin using the eFlow® or LCplus® nebulizer was published in 2010. In cystic fibrosis patients, the deposit in lungs was lower with eFlow®, although it was not a significant difference. Nebulization time was significantly shorter with eFlow (7 min vs. 20 min, p<0.05).Also, between 2009 and 2011, 3 studies were published (range: 15-59 patients) which were conducted on cystic fibrosis subjects, and before (conventional nebulizer) and after (eFlow®) data were compared. No statistically significant differences were found in the respiratory performance parameters assessed or in the tobramycin dose administered. Nebulization time was statistically shorter with eFlow® in the three studies as well as the rate of satisfaction. In one of the studies, the eFlow® device early stopped in 51% of the cases due to hole obstruction, which reduced the administered dose and suggested the need for proper device cleaning.The European Consensus on Inhaled Drugs and Devices for cystic fibrosis patients mentions that using eFlow®: a) the pulmonary doses is 32% versus 16% when using PARI LC®, and 63-73% when using I-neb®; b) residual volume is approximately 28% with eFlow®, being 38% and 61% with the conventional devices; c) it is not clear whether eFlow keeps on supplying the full dose when used longer than 6 months; d) drug loss is estimated in 34% for eFlow®, and 1% for I-neb®. There are no recommendations as regards eFlow®.The Australia and New Zealand Horizon Scanning Network (ANZHSN) mentions that there are few studies comparing eFlow® with another nebulizer in patients with cystic fibrosis. It mentions a shorter nebulization time than with other conventional nebulizers and considers that this should be taken into account due to a potential better adherence that might provide better results.The guidelines published by the United Kingdom Royal Brompton Hospital describe that the pros of eFlow® are that it may be used with any drug, it provides fast nebulization, it is silent and may be used at any age. Cons include that it is not activated by respiration and that some drug may be lost during exhalation, that antibiotics require filter and that it takes longer to clean it.Not many coverage policies have been found which specifically mention the type of nebulizer to be used in cystic fibrosis, and the health sponsors relieved do not mention eFlow®, although they mention other types of nebulizers.Its cost is estimated in $14,750 (Argentine pesos, January, 2012) versus approximately $300 (Argentine pesos, January, 2012) which is the cost of conventional devices.ConclusionsThe information included in this report comes from small, low methodological quality studies and most of them do not report relevant clinical results.The only advantage shown in the published studies is shorter nebulization time with eFlow® when compared with conventional devices. However, this does not show relevant clinical benefits beyond its potential better adherence. Also, one study mentions that its performance may decrease after 6 months in use. In addition, there are other nebulizers (e.g., I-neb®) with which it may be compared, since they have potential advantages.So far, based on the evidence found, there is no evidence that shows the clinical benefit of eFlow® over conventional devices beyond nebulization times. More properly designed studies are required to assess if eFlow® would have a relevant benefit in patients with cystic fibrosis.