Safety Study of Aztreonam Lysine for Inhalation (AZLI) in the Treatment of Early Bronchiolitis Obliterans Syndrome (BOS)

Condition(s) targeted: Complication of Transplanted Lung

Intervention: Aztreonam Lysine for Inhalation (AZLI) (Drug); Status Post Lung Transplant (Procedure)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: Duke University

Official(s) and/or principal investigator(s):
Scott Palmer, MD, Principal Investigator, Affiliation: Duke University

Overall contact:
Scott Palmer, MD, Phone: 919-668-5111, Email: palme002@mc.duke.edu

This study is a pilot two- center study to determine if aztreonam lysine for inhalation AZLI can be safely and continuously administered over 4 month period in lung transplant recipients with bronchiolitis obliterans syndrome (BOS) and obtain pilot data regarding its effect on lung function in order to appropriately design and power a larger multicenter randomized study.

The hypothesis is that AZLI is a safe and effective treatment for declining lung function in lung transplant recipients with early stage BOS.

Official title: Aztreonam Lysine for Inhalation (AZLI) in the Treatment of Early Bronchiolitis Obliterans Syndrome (BOS) After Lung Transplantation

Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Change in FEV1 from enrollment to study completion

Secondary outcome:

Number of participants with adverse events as a measure of safety or tolerability

Number of patients that complete the full treatment course

Changes in lung fluid biomarkers after completion of treatment as compared to baseline values

Detailed description: Lung transplantation is increasingly employed as a therapy for patients with advanced lung disease including cystic fibrosis, idiopathic pulmonary fibrosis or emphysema. Despite significant short-term improvements in life quality and measures of lung function after lung transplantation, long-term outcomes are disappointing primarily due to the development of a condition of airway fibrosis known as bronchiolitis obliterans (BO). It is hypothesized that aztreonam lysine for inhalation (AZLI) is a safe and effective treatment for declining lung function in lung transplant recipients with early stage BOS. In order to test the hypothesis, the investigators seek to establish the safety of AZLI in a two-center cohort of 30 lung transplant recipients with BOS treated continuously for 4 months and determine if this treatment leads to improvement or stabilization of lung function. The intervention will involve open label treatment with AZLI, in addition to usual transplant care, administered continuously for the 4-month patient involvement in the study. Bronchoscopy, pulmonary function testing, and laboratory testing will be performed on a regular basis during study enrollment consistent with each center's usual standard clinical care. Patients will have a baseline screening visit, a 2 months study visit and a closeout visit at 4 months. The study will take two years to complete from the start of funding. After a start-up period of 2 months, a total of 30 patients will be enrolled over 12 months across the two centers (15 patients each at DUMC and UCLA). Each enrolled patient will complete 4 months of continuous therapy, and complete baseline, on study, and study termination visits. Over the next 6 months the study database will be finalized, statistical analysis will for primary and secondary outcomes will be performed leading to the generation of either a study abstract or manuscript.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Adult (18 or older)

- Cadaveric first lung transplant recipient, single or bilateral

- Current FEV1 66-80% of posttransplant baseline FEV1, and meets all criteria for BOS 1

as defined by the ISHLT.

- Onset of BOS diagnosis within one year

- No other BOS treatments initiated within one month prior to enrollment; if patients

are already on azithromycin its use is permitted without change during the study.

- No changes in BOS treatments over the course of the study

- Non-pregnant females

Exclusion Criteria:

- Known allergy to aztreonam

- Retransplant

- Pediatric patients

- Multiorgan transplant recipients

- Live lobar transplant recipients

- Anticipation of the need for additional BOS treatments during the study

- Inability to provide informed consent.

- Patients with advanced BOS (grades 2,3) or established BOS >6 months

Scott Palmer, MD, Phone: 919-668-5111, Email: palme002@mc.duke.edu

David Geffen School of Medicine at UCLA, Los Angeles, California 90095, United States; Not yet recruiting
John Belpreio, MD, Principal Investigator

Duke University Medical Center, Durham, North Carolina 27710, United States; Not yet recruiting
Scott Palmer, MD, Principal Investigator

Related publications:

Belperio JA, Weigt SS, Fishbein MC, Lynch JP 3rd. Chronic lung allograft rejection: mechanisms and therapy. Proc Am Thorac Soc. 2009 Jan 15;6(1):108-21. Review.

Weigt SS, Wallace WD, Derhovanessian A, Saggar R, Saggar R, Lynch JP, Belperio JA. Chronic allograft rejection: epidemiology, diagnosis, pathogenesis, and treatment. Semin Respir Crit Care Med. 2010 Apr;31(2):189-207. Epub 2010 Mar 30. Review.

Estenne M, Maurer JR, Boehler A, Egan JJ, Frost A, Hertz M, Mallory GB, Snell GI, Yousem S. Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria. J Heart Lung Transplant. 2002 Mar;21(3):297-310. Review. No abstract available.

Lama VN, Murray S, Lonigro RJ, Toews GB, Chang A, Lau C, Flint A, Chan KM, Martinez FJ. Course of FEV(1) after onset of bronchiolitis obliterans syndrome in lung transplant recipients. Am J Respir Crit Care Med. 2007 Jun 1;175(11):1192-8. Epub 2007 Mar 8.

Christie JD, Edwards LB, Kucheryavaya AY, Aurora P, Dobbels F, Kirk R, Rahmel AO, Stehlik J, Hertz MI. The Registry of the International Society for Heart and Lung Transplantation: twenty-seventh official adult lung and heart-lung transplant report--2010. J Heart Lung Transplant. 2010 Oct;29(10):1104-18. No abstract available.

Finlen Copeland CA, Snyder LD, Zaas DW, Turbyfill WJ, Davis WA, Palmer SM. Survival after bronchiolitis obliterans syndrome among bilateral lung transplant recipients. Am J Respir Crit Care Med. 2010 Sep 15;182(6):784-9. Epub 2010 May 27.

Vos R, Vanaudenaerde BM, Ottevaere A, Verleden SE, De Vleeschauwer SI, Willems-Widyastuti A, Wauters S, Van Raemdonck DE, Nawrot TS, Dupont LJ, Verleden GM. Long-term azithromycin therapy for bronchiolitis obliterans syndrome: divide and conquer? J Heart Lung Transplant. 2010 Dec;29(12):1358-68. Epub 2010 Jul 8.

Gerhardt SG, McDyer JF, Girgis RE, Conte JV, Yang SC, Orens JB. Maintenance azithromycin therapy for bronchiolitis obliterans syndrome: results of a pilot study. Am J Respir Crit Care Med. 2003 Jul 1;168(1):121-5. Epub 2003 Apr 2.

Vos R, Vanaudenaerde BM, Geudens N, Dupont LJ, Van Raemdonck DE, Verleden GM. Pseudomonal airway colonisation: risk factor for bronchiolitis obliterans syndrome after lung transplantation? Eur Respir J. 2008 May;31(5):1037-45. Epub 2008 Feb 6.

Jain R, Hachem RR, Morrell MR, Trulock EP, Chakinala MM, Yusen RD, Huang HJ, Mohanakumar T, Patterson GA, Walter MJ. Azithromycin is associated with increased survival in lung transplant recipients with bronchiolitis obliterans syndrome. J Heart Lung Transplant. 2010 May;29(5):531-7. Epub 2010 Feb 4.

McCoy KS, Quittner AL, Oermann CM, Gibson RL, Retsch-Bogart GZ, Montgomery AB. Inhaled aztreonam lysine for chronic airway Pseudomonas aeruginosa in cystic fibrosis. Am J Respir Crit Care Med. 2008 Nov 1;178(9):921-8. Epub 2008 Jul 24.

Oermann CM, Retsch-Bogart GZ, Quittner AL, Gibson RL, McCoy KS, Montgomery AB, Cooper PJ. An 18-month study of the safety and efficacy of repeated courses of inhaled aztreonam lysine in cystic fibrosis. Pediatr Pulmonol. 2010 Nov;45(11):1121-34.

Starting date: December 2012
Last updated: November 26, 2012