Complication of Transplanted Lung Clinical Trial
— AZLIOfficial title:
Aztreonam Lysine for Inhalation (AZLI) in the Treatment of Early Bronchiolitis Obliterans Syndrome (BOS) After Lung Transplantation
| Verified date | December 2015 |
| Source | Duke University |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | United States: Institutional Review Board |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 30 |
| Est. completion date | April 2015 |
| Est. primary completion date | March 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
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 |
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United States | Duke University Medical Center | Durham | North Carolina |
| United States | David Geffen School of Medicine at UCLA | Los Angeles | California |
| Lead Sponsor | Collaborator |
|---|---|
| Duke University | Gilead Sciences |
United States,
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. Review. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. Review. — View Citation
* Note: There are 12 references in all — Click here to view all references
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Change in Pulmonary Function, as Measured by Serial Forced Expiratory Volume in 1 Second (FEV1) on Spirometry | Within-subject change to absolute FEV1 month 1 vs. 0. FEV1 was measured 14-35 days after the start of months 1 AZLI courses and compared to study month 0 (baseline/prior to 1st dose). | Baseline, month 1 | No |
| Primary | Change in Pulmonary Function, as Measured by Serial Forced Expiratory Volume in 1 Second (FEV1) on Spirometry | Within-subject change to absolute FEV1 month 5 vs 0. | Baseline, month 5 | No |
| Primary | Change in Global Health Related Quality of Life, Measured by Serially Self-administered Short Form 36 Health Survey Questionnaire (SF-36) at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 1 | The SF-36 is a commonly used, well validated measure of global health related quality of life. The survey was self-administered. There are 8 subscales which combine to form a Physical Component Score (PCS) and a Mental Component Score (MCS). We analyzed within subject changes to the PCS and MCS at month 1 vs. 0. MCS and PCS scores are relative to a US population mean of 50. The higher the score, the better one perceives his quality of life. A change in score of 4 points or more is considered clinically meaningful. Scores represent Median Absolute Difference. The SF-36 was completed 14-35 days after the start of months 1 AZLI courses and compared to study month 0 (baseline/prior to 1st dose). | Baseline, month 1 | No |
| Primary | Change in Global Health Related Quality of Life, Measured by Serially Self-administered Short Form 36 Health Survey Questionnaire (SF-36) at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 1 and Month 5. | The SF-36 is a commonly used, well validated measure of global health related quality of life. The survey was self-administered. There are 8 subscales which combine to form a Physical Component Score (PCS) and a Mental Component Score (MCS). We analyzed within subject changes to the PCS and MCS at month 5 vs 0. MCS and PCS scores are relative to a US population mean of 50. The higher the score, the better one perceives his quality of life. A change in score of 4 points or more is considered clinically meaningful. Scores represent Median Absolute Difference. The SF-36 was completed 14-35 days after the start of months 1 and 5 AZLI courses and compared to study month 0 (baseline/prior to 1st dose). | Baseline, month 5 | No |
| Primary | Change in Respiratory-specific Health Related Quality of Life, Measured by Serially Self Administered St. George's Respiratory Questionnaire (SGRQ) at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 1 | The SRGQ measures activities, symptoms, and impacts of living with a pulmonary condition. We analyzed the change to the within-subject Total score month 1 vs. 0. Total score ranges from 0-100 with a smaller value representing better respiratory-specific QOL. A change in score of 4 points or more is considered clinically meaningful. Scores represent Median Absolute Difference in the Total Score. The SGRQ was completed 14-35 days after the start of months 1 AZLI courses and compared to study month 0 (baseline/prior to 1st dose). | Baseline, month 1 | No |
| Primary | Change in Respiratory-specific Health Related Quality of Life, Measured by Serially Self Administered St. George's Respiratory Questionnaire (SGRQ) at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 5. | The SRGQ measures activities, symptoms, and impacts of living with a pulmonary condition. We analyzed the change to the within-subject Total score month 5 vs 0. Total score ranges from 0-100 with a smaller value representing better respiratory-specific QOL. A change in score of 4 points or more is considered clinically meaningful. Scores represent Median Absolute Difference in theTotal Score. The SGRQ was completed 14-35 days after the start of month 5 AZLI courses and compared to study month 0 (baseline/prior to 1st dose). | Baseline, month 5 | No |
| Primary | Change in Pulmonary Function, as Measured by Serial Forced Expiratory Flow (FEF25-75) on Spirometry at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 5. | Within-subject change to absolute FEF 25-75 month 5 vs 0. FEF 25-75 was measured 14-35 days after the start of months 5 | Baseline, month 5 | No |
| Primary | Change in Pulmonary Function, as Measured by Serial Forced Expiratory Flow (FEF25-75) on Spirometry at Baseline (Prior to AZLI First Dose) and During AZLI Therapy at Month 1 | Within-subject change to absolute FEF 25-75 month 1 vs. 0. FEF 25-75 was measured 14-35 days after the start of months 1 | Baseline, month 1 | No |
| Secondary | Change in FEV1 Off AZLI Therapy | This will be compared to study month 0 (baseline, when obtained as standard of care (SOC). | At Study Months 2 and 4 | Yes |
| Secondary | Change in HRQOL Off AZLI Therapy. | This will be compared to study month 0 (baseline), when obtained at standard of care visit (SOC) | At study months 2 or 4 | Yes |
| Secondary | Among Patients Colonized With Pseudomonas Aeruginosa, Change in Infection Burden as Measured by the Culture Final Report (0,1+, 2+, 3+, 4+) of in Pseudomonas Aeruginosa Sputum or Bronchoalveolar Fluid. | Microbiology data was collected when performed for SOC purposes on BAL or sputum samples. Baseline and 1 month value represents the culture final report value (0,1+, 2+, 3+, 4+) of Pseudomonas aeruginosa. A value of zero represents no Pseudomonas aeruginosa sputum or bronchoalveolar fluid. A value of 4 represents high amounts of Pseudomonas aeruginosa sputum or bronchoalveolar fluid. | Baseline, month 1 | Yes |
| Secondary | Bronchoalveolar Lavage Fluid (BALF) Neutrophilia After Treatment, When Performed as Part of Clinical Care (SOC). | The study team is measuring the change in neutrophils AFTER treatment. They will compare a SOC BAL taken after AZLI with the BAL taken within 90 days of AZLI initiation (pre or baseline measure). The post AZLI BAL measurement time range is 15 days after first course of AZLI up to last day of the 3rd and final course of AZLI (over a period of 5 consecutive months). | Baseline - defined as a within 90 days of enrollment and After Treatment (5 months) | Yes |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00584077 -
Assessment of Cough Reflex in Lung Transplant Recipients
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