| Citation |
Castro M, Rubin AS, Laviolette M, Fiterman J, De Andrade Lima M, Shah PL, Fiss E, Olivenstein R, Thomson NC, Niven RM, Pavord ID, Simoff M, et al. |
| Objective |
The objective of this randomized, double blind, sham-controlled study was to demonstrate the safety and effectiveness of the Alair® Bronchial Thermoplasty System in a population of subjects with severe asthma who are still symptomatic despite being managed on conventional therapy of high doses of inhaled corticosteroids (ICS – doses greater than 1000?g per day beclomethasone or equivalent) and long-acting ?2-agonists (LABA – doses of at least 100?g per day salmeterol or equivalent). |
| Design |
An international, multi-center, randomized, double-blind sham-controlled trial conducted at 30 Investigational Sites in 6 countries comparing the effects of treatment with the Alair® Bronchial Thermoplasty System plus conventional drug therapy of ICS and LABA with sham bronchoscopy plus conventional drug therapy of ICS and LABA. Subjects meeting the inclusion/exclusion criteria underwent baseline evaluations, followed by bronchial thermoplasty (BT) Treatment or Sham bronchoscopy procedures (depending upon randomization), and underwent follow-up evaluations at 3-, 6-, 9-, and 12-months post procedure. Long-term follow up of BT treated patients to include annual visits out to 5 years. |
| Blinding |
Separate teams of study personnel were employed at each site in order to maintain blinding of the study. The unblinded team (Bronchoscopy Team) performed both the Sham and BT procedures. A separate blinded team (Assessment Team) conducted the baseline and post-procedure follow-up evaluations on the subjects. All study subjects were blinded. |
| Methods |
Subjects in the BT Group received the Alair® treatment during three separate bronchoscopy sessions while subjects in the Sham Group received three separate sham bronchoscopy procedures. All subjects continued on their prescribed maintenance asthma medications throughout the study. All subjects completed follow-up evaluations at 3 months, 6 months, 9 months, and 12 months after the last bronchoscopy session. Subjects were required to record in a diary their peak expiratory flow rates, asthma symptoms, and rescue medication usage for pre-specified periods throughout the study. Following the 12 month evaluation, Sham group subjects were exited from the study, while BT Group subjects will complete 4 subsequent annual follow-up evaluations for safety. The blind was broken at the 12-month visit. |
| Primary Endpoint |
Difference between study groups in the change in Asthma Quality of Life Questionnaire (AQLQ) scores from baseline to the integrated score at 6, 9, and 12 month evaluations. |
| Secondary Endpoints |
|
| Safety |
Safety was assessed by comparing the incidence and types of adverse events reported for the subjects in each group during the Treatment Period (day of 1st bronchoscopy till 6 weeks after the 3rd bronchoscopy), and the Post-Treatment Period (from 6 weeks after the 3rd bronchoscopy till 12 months). Safety was also assessed by comparing unscheduled physicians office visits for respiratory symptoms, emergency room visits for respiratory symptoms, and hospitalizations for respiratory symptoms. |
| Results |
A total of 297 Subjects (18-65 years) meeting study inclusion/exclusion criteria were randomized to the BT group (196) or a Sham group (101) in a 2 to 1 randomization scheme. 288 subjects (190 BT group and 98 Sham group) underwent the bronchoscopy procedures. Effectiveness Key findings for BT treated patients versus Sham during the Post-Treatrment Period:
Safety
Post-Treatment Phase
|
| Conclusions |
BT delivered by the Alair® System provides long term asthma control in patients with severe asthma out to one year The Alair® System is safe and effective for the treatment of severe persistent asthma in adults |
| AIR2 Trial: Participating Institutions and Investigators | ||
|---|---|---|
| United States | ||
| Institution | Principal Investigator | Co-Investigator |
| Baylor College of Medicine, Houston, TX | William Lunn, MD | Nicola Hanania, MD |
| Brigham & Women’s Hospital, Boston, MA | Michael Wechsler, MD | Elliot Israel, MD |
| Cleveland Clinic Foundation, Cleveland, OH | Serpil Erzurum, MD | Tom Gildea, MD Atul Mehta, MD |
| Duke University Medical Center, Durham, NC | Monica Kraft, MD | Momen Wahidi, MD |
| Health Partners Specialty Center, Regions Hospital, St. Paul, MN | Charlene McEvoy, MD | Krista Graven, MD |
| Henry Ford Hospital, Detroit, MI | Michael Simoff, MD | Edward Zoratti, MD |
| Johns Hopkins University School Medicine, Baltimore, MD | Rex Yung, MD | Nadia Hansel, MD |
| Swedish Medical Center, Seattle, WA | Brian Louie, MD | Linda Anderson, MD |
| University of Chicago, Chicago, IL | Imre Noth, MD | Kyle Hogarth, MD |
| University of Iowa, Iowa City, IO | Geoffrey McLennan, MD | Joel Kline, MD |
| University of Pennsylvania, Philadelphia, PA | Daniel Sterman, MD | Ali Musani, MD Michael Sims, MD |
| USC School of Medicine, Los Angeles, CA | Richard Barbers, MD | Ricardo Juarez, MD |
| Veritas Clinical Specialties, Topeka, KS | William Leeds, MD | Laura Ludlow, PA |
| Virginia Hospital Center, Arlington, VA | David Duhamel, MD | Jeff Hales, MD |
| Washington University School of Medicine, St. Louis, MO | Mario Castro, MD | Martin Mayse, MD |
| AIR2 Trial: Participating Institutions and Investigators | ||
|---|---|---|
| Canada | ||
| Institution | Principal Investigator | Co-Investigator |
| Hôpital Laval, Sainte-Foy, Quebec, Canada | Michel Laviolette, MD | Simon Martel, MD Louis-Phillipe Boulet, MD |
| Montreal Chest Institute, Montreal, Canada | Ronald Olivenstein, MD | Jean Bourbeau, MD |
| St. Joseph’s Healthcare, Hamilton, Ontario, Canada | Gerard Cox, MD | John Miller, MD |
| Europe | ||
| Institution | Principal Investigator | Co-Investigator |
| Birmingham Heartlands Hosp., Birmingham, UK | Adel Mansur, MD | Sherwood Burge, MD |
| Chelsea & Westminster Hosp., London, UK | Pallav Shah, MD | Suveer Singh, MD |
| Gartnavel General Hosp., Univ. Glasgow, Glasgow, UK | Neil Thompson, MD | Rekha Chaudhuri, MD |
| Glenfield General Hospital, Leicester, UK | Ian Pavord, MD | Neil Martin, MD |
| Wythenshawe Hosp., Univ. of Manchester, Manchester, UK | Robert Niven, MD | Tony Pickering, MD Curig Prys-Picard. MD |
| University Hospital Groningen, Groningen, The Netherlands | Nicolaas HT ten Hacken, MD | Dirk-Jan Slebos, MD |
| Australia | ||
| Institution | Principal Investigator | Co-Investigator |
| Royal Adelaide Hospital, Adelaide, Australia | Mark Holmes, MD | Hubertus Jersmann, MD |
| Sir Charles Gairdner Hospital, Perth, Australia | Martin Phillips, MD | Kerry Boughton |
| Brazil | ||
| Institution | Principal Investigator | Co-Investigator |
| Faculdade de Medicina do ABC, Sao Paulo, Brazil | Elie Fiss, MD | Claudio Rufino Gomes, Jr., MD Maria Enedina, MD |
| Hospital São Lucas da PUCRS, Porto Alegre, Brazil | Jussara Fiterman, MD | Virgilio Tonietto, MD Fábio M Haggsträm, MD |
| Hospital Univeritario Clementino Graga Filho, Rio de Janiero, Brazil | Jose Roberto Lapa, MD | Marina de Andrade Lima, MD |
| Irmandade Santa Casa de Misericórdia Porto Alegre, Brazil | Adalberto S Rubin, MD | Paulo Cardoso, MD Manuela Cavalcanti, MD |
