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

NCT ID: NCT01469364

Last Updated: 2016-01-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2015-04-30

Brief Summary

This study is a pilot two- center study to determine if aztreonam lysine for inhalation AZLI can be safely and self-administered in lung transplant recipients with newly diagnosed bronchiolitis obliterans syndrome, grade 1 (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.

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 intermittently for 5 consecutive study 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 for 3 intermittent courses, 28 days each, over a 5 month study period.. 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, one month and five month study visit.. 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 5 months of intermittent therapy, and complete baseline, month 1 and month 5 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.

Conditions

Complication of Transplanted Lung

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Aztreonam Lysine for Inhalation (AZLI)

Patients to received Aztreonam Lysine(AZLI)

Group Type: EXPERIMENTAL

Aztreonam Lysine for Inhalation (AZLI)

Intervention Type: DRUG

The intervention will involve open label treatment with AZLI inhaled 75mg TID self-administered intermittently for 28 days on study drug and 28 days off study drug over a study period of 5 consecutive months (on/off/on/off/on AZLI)

Status Post Lung Transplant

Intervention Type: PROCEDURE

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.

Interventions

Aztreonam Lysine for Inhalation (AZLI)

The intervention will involve open label treatment with AZLI inhaled 75mg TID self-administered intermittently for 28 days on study drug and 28 days off study drug over a study period of 5 consecutive months (on/off/on/off/on AZLI)

Intervention Type: DRUG

Status Post Lung Transplant

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.

Intervention Type: PROCEDURE

Other Intervention Names

Standard Post Lung Transplant Care

Eligibility Criteria

Inclusion Criteria

• Adult (18 or older at the time of transplant) male or female
• Cadaveric first lung transplant recipient, single or bilateral; or multi-organ lung transplant recipient.
• Current FEV1 66-80% of posttransplant baseline FEV1, and meets all criteria for BOS 1 as defined by the International Society of Heart and Lung Transplantation.

• Onset of BOS 1 within twelve months of screening

Exclusion Criteria

• Known allergy to aztreonam
• Retransplant
• Pediatric patients
• Live lobar transplant recipients
• Inability to provide informed consent.
• Patients with advanced BOS (grades 2,3) or established BOS >6 months
• Pregnant Women

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Scott Palmer, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

References

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. doi: 10.1513/pats.200807-073GO.

Reference Type: BACKGROUND

PMID: 19131536 (View on PubMed)

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. doi: 10.1055/s-0030-1249116. Epub 2010 Mar 30.

Reference Type: BACKGROUND

PMID: 20354932 (View on PubMed)

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. doi: 10.1016/s1053-2498(02)00398-4. No abstract available.

Reference Type: BACKGROUND

PMID: 11897517 (View on PubMed)

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. doi: 10.1164/rccm.200609-1344OC. Epub 2007 Mar 8.

Reference Type: BACKGROUND

PMID: 17347496 (View on PubMed)

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. doi: 10.1016/j.healun.2010.08.004. No abstract available.

Reference Type: BACKGROUND

PMID: 20870165 (View on PubMed)

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. doi: 10.1164/rccm.201002-0211OC. Epub 2010 May 27.

Reference Type: BACKGROUND

PMID: 20508211 (View on PubMed)

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. doi: 10.1016/j.healun.2010.05.023. Epub 2010 Jul 8.

Reference Type: BACKGROUND

PMID: 20619683 (View on PubMed)

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. doi: 10.1164/rccm.200212-1424BC. Epub 2003 Apr 2.

Reference Type: BACKGROUND

PMID: 12672648 (View on PubMed)

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. doi: 10.1183/09031936.00128607. Epub 2008 Feb 6.

Reference Type: BACKGROUND

PMID: 18256072 (View on PubMed)

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. doi: 10.1016/j.healun.2009.12.003. Epub 2010 Feb 4.

Reference Type: BACKGROUND

PMID: 20133163 (View on PubMed)

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. doi: 10.1164/rccm.200712-1804OC. Epub 2008 Jul 24.

Reference Type: BACKGROUND

PMID: 18658109 (View on PubMed)

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. doi: 10.1002/ppul.21301.

Reference Type: BACKGROUND

PMID: 20672296 (View on PubMed)

Other Identifiers

Gilead Sciences, Inc

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00030191

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00030559

Identifier Type: -

Identifier Source: org_study_id