No Disclosures Lung in a Box Ex vivo Lung Perfusion (EVLP) Jasleen - PDF document

5/31/2013 Critical Care Medicine & Trauma Conference 2013 No Disclosures “Lung in a Box” Ex vivo Lung Perfusion (EVLP) Jasleen Kukreja, M.D., M.P.H. Program & Surgical Director, Lung Transplant University of California San Francisco Increasing waiting list has not been Lung Transplant Facts matched with donation rate • As of Februrary 8, 2013, 1658 patients waiting for lung transplant in 70 Lung transplant • Only 15-20% offered programs in the U.S lungs accepted; 80% rejected due to: • California has the highest number on waitlist - poor quality - prolonged ischemia • >50% wait more than 6 months on the list time • 12% to 15% die waiting for suitable organs 4 1

5/31/2013 Supply : Demand Optimizing Supply : Demand Ratio • Recipient selection criteria – Age – Diagnosis – Single vs double lung transplant 5 6 LUNG TRANSPLANTS: LUNG TRANSPLANTATION Transplant Recipient Age by Year of Transplant Kaplan-Meier Survival by Age Group (Transplants: January 1990 – June 2009) Transplants: January 1, 1987 – June 30, 2010 100 HALF-LIFE 18-34: 6.4 Years; 35-49: 6.7 Years; 50-59: 5.3 Years; 60-65: 4.4 Years; >65: 3.5 100% 60 Years Median recipient age (years) 80 80% 48 Survival comparisons % of transplantsrs All p-values significant at p < 0.0001 except 18-34 vs. 35-49: p =0.1708 60% 36 Survival (%) 60 40% 24 40 20% 12 18-34 (N = 5,523) 35-49 (N = 7,980) 20 50-59 (N = 11,389) 0% 0 60-65 (N = 5,685) 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 >65 (N = 1,217) Year of Transplant 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 0-11 12-17 18-34 35-49 50-59 60-65 66+ Median Age Years ISHLT ISHLT 2011 2011 J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132 J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132 2

5/31/2013 LUNG TRANSPLANTATION Single vs Double Lung Transplant Kaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2009) 100 Alpha-1 (N=2,349) CF (N=4,828) COPD (N=10,741) IPF (N=6,478) IPAH (N=1,189) Sarcoidosis (N=756) 80 HALF-LIFE Alpha-1: 6.3 Years; CF: 7.4 Years; COPD: 5.3 Years; IPF: 4.5 Years; IPAH: 4.9 Years; Sarcoidosis: 5.3 Years Survival (%) 60 40 Single Lung Single Lung Survival comparisons All comparisons with Alpha-1 and CF are 20 statistically significant at < 0.01 COPD vs. IPF: p < 0.0001 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Years ISHLT 2011 J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132 ADULT LUNG TRANSPLANTATION Optimizing Supply : Demand Ratio Kaplan-Meier Survival (Transplants: January 1994 - June 2009) 100 Double lung: 1/2-life = 6.8 Years; Single lung: 1/2-life = 4.7 Years All lungs: 1/2-life = 5.5 Years • Recipient selection • Donor selection criteria: 80 criteria: Survival (%) 60 – Age P < 0.0001 -Age – Diagnosis 40 -Single vs double lung – Single vs double lung transplant Bilateral/Double Lung (N=16,628) transplant 20 Single Lung (N=12,085) All Lungs (N= 28,727) 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Years ISHLT 2011 12 J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132 3

5/31/2013 LUNG TRANSPLANTS: ADULT LUNG TRANSPLANTS (1/1997-6/2005) Donor Age by Year of Transplant Risk Factors for 5 Year Mortality Donor Age Transplants: January 1, 1987 – June 30, 2010 Relative Risk of 5 Year Mortality 50 100% 2 Median donor age (years) 80% 40 % of transplants 1.5 60% 30 1 40% 20 20% 10 0.5 p = 0.0646 0% 0 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 7 8 9 0 8 8 8 9 9 9 9 9 9 9 9 9 9 0 0 0 0 0 0 0 0 0 0 1 9 9 9 9 9 9 9 9 9 9 9 9 9 0 0 0 0 0 0 0 0 0 0 0 0 1 1 1 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 2 Year of Transplant 15 20 25 30 35 40 45 50 55 Donor Age 0-11 12-17 18-34 35-49 50-59 60+ Median Donor Age ISHLT ISHLT 2011 2011 J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132 J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132 Standard Lung Procurement Optimizing Supply : Demand Ratio • Recipient selection • Donor selection criteria: criteria: -Age – Age -Single vs double – Diagnosis -Rehabilitation/ – Single vs double lung reconditioning transplant 15 4

5/31/2013 “Lungs in a Box” • Bronchoscopy • Antibiotic treatment • Constant Monitoring – Dynamic compliance – Peak Inspiratory pressure – Pulmonary vascular resistance – P/F ratio Ex Vivo Reconditioning Donor Lungs Transplantation Proceedings, 42, 440 – 443 (2010) 5

5/31/2013 Normothermic Ex-vivo Perfusion in Lung Transplant N Engl J Med 364;15 April 14, 2011 High Risk Donors: • Inclusion Criteria: • PaO2/FiO2 < 300 mm Hg • Bilateral infiltrates w/o infection • Poor lung deflation or inflation intraoperatively • Blood transfusions exceeding 10 Units • Donation after cardiac death • Exclusion Criteria: • Established pneumonia • Mechanical lung injury From the Toronto Lung Transplant Program • Gross gastric aspiration N Engl J Med 2011;364:1431-40 . 6

5/31/2013 U.S. NOVEL Lung Trial Marginal Donor Lungs ADULT LUNG TRANSPLANT RECIPIENTS: OCS INSPIRE Trial Relative Incidence of Leading Causes of Death International Randomized Trial (Deaths: January 1992 - June 2010) 50 Bronchiolitis Malignancy (non-Lymph/PTLD) Infection (non-CMV) Graft Failure Goals: To compare the safety and Cardiovascular 40 effectiveness of the OCS Lung Percentage of Deaths compared to cold storage for donor lung preservation 30 Design: A prospective, international, multi- 20 center, randomized controlled trial comparing preservation of donor 10 lungs using OCS-Lung perfusion device (Treatment Group) to cold 0 flush and storage (Control Group) 0-30 Days 31 Days – 1 >1 Year – 3 >3 Years – 5 >5 Years – 10 >10 Years (N=2,204) Year Years Years Years (N=675) Size: Up-to 20 participating sites with up to (N=3,781) (N=3,425) (N=1,962) (N=2,336) 264 randomized male and female subjects who are primary lung transplant recipients. ISHLT 2011 J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132 7

5/31/2013 OCS™ Lung Technology INSPIRE Endpoints Primary: A composite of patient and graft survival at day 30 post transplantation, and absence of ISHLT Primary Graft Dysfunction (PGD) Grade 3 at 72 hours post-transplantation. Secondary: • Incidence of ISHLT PGD Grade 3 at 72 hours post-transplantation • Incidence of ISHLT PGD Grade 2 or 3 at 72 hours post-transplantation • Patient survival at day 30 • Graft survival at day 30 The ONLY Portable, Integrated and Automated Perfusion & Ventilation System INSPIRE Trial Centers To-Date Early Clinical Experience • OCS Lung was released in the European market EU Sites US Sites Australia in Jan 2011 Hannover Sydney • Between February-July 2011, 13 double lung Berlin Cleveland Clinic transplant procedures on the OCS™ -Lung Madrid UCLA device Padua Canada UPMC • Non-randomized and were consecutive case Leuven The Methodist series at Hannover Medical School, Hannover, Strasbourg Edmonton UCSF Germany and Puerta de Hierro Majdahonda Bichat Harefield Hospital, Madrid, Spain Leuven 8

5/31/2013 Early outcome Post transplant outcomes OCS SOC (N=9) (N=10) ICU time (hours) Mean +/- SD 170+/-350 97+/-91 Median 50 65 Range 15 - 1033 16 - 276 The INSPIRE International Lung Trial Mechanical ventilation time (hours) With The Organ Care System Mean +/- SD 14.4+/-5.5 15.5+/-5.6 Technology (OCS™) Median 14.5 15.0 Range 5 - 22 9 - 27 G. Warnecke, A. Haverich, G. Massard, N. Santelmo, F. Rea, C. Knosalla, R. Hetzer, Survival at 30 days Patient [n(%)] 6 (100) 7 (100) G. Leseche, A. Ardehali, A. R. Simon, J. Kukreja, K. McCurrey Graft [n(%)] 6 (100) 7 (100) Primary Graft Dysfunction (PGD) Grade 3 T 0 [n(%)] 0 (0) 2 (20) T 24 [n(%)] 0 (0) 0 (0) T 48 [n(%)] 0 (0) 1 (11) T 72 [n(%)] 0 (0) 1 (11) “Lung in a Box” might be the ANSWER! Improved Survival Increased Supply Thank You ! 35 9