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

5/31/2013 1

Jasleen Kukreja, M.D., M.P.H. Program & Surgical Director, Lung Transplant University of California San Francisco

“Lung in a Box” Ex vivo Lung Perfusion (EVLP)

Critical Care Medicine & Trauma Conference 2013

No Disclosures Lung Transplant Facts

• As of Februrary 8, 2013, 1658 patients waiting

for lung transplant in 70 Lung transplant programs in the U.S

• California has the highest number on waitlist
• >50% wait more than 6 months on the list
• 12% to 15% die waiting for suitable organs

Increasing waiting list has not been matched with donation rate

• Only 15-20% offered

lungs accepted; 80% rejected due to:

• poor quality
• prolonged ischemia

time

4

5/31/2013 2

Supply : Demand

5

Optimizing Supply : Demand Ratio

• Recipient selection criteria

– Age – Diagnosis – Single vs double lung transplant

6

LUNG TRANSPLANTATION

Kaplan-Meier Survival by Age Group (Transplants: January 1990 – June 2009)

20 40 60 80 100 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Years

18-34 (N = 5,523) 35-49 (N = 7,980) 50-59 (N = 11,389) 60-65 (N = 5,685) >65 (N = 1,217)

Survival comparisons All p-values significant at p < 0.0001 except 18-34 vs. 35-49: p =0.1708 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 Years

Survival (%)

ISHLT

2011

J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132

LUNG TRANSPLANTS:

Transplant Recipient Age by Year of Transplant

Transplants: January 1, 1987 – June 30, 2010

0% 20% 40% 60% 80% 100%

1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

12 24 36 48 60 0-11 12-17 18-34 35-49 50-59 60-65 66+ Median Age

Median recipient age (years) % of transplantsrs Year of Transplant

ISHLT

2011

J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132

5/31/2013 3

LUNG TRANSPLANTATION

Kaplan-Meier Survival By Diagnosis (Transplants: January 1990 – June 2009)

20 40 60 80 100 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Years Survival (%)

Alpha-1 (N=2,349) CF (N=4,828) COPD (N=10,741) IPF (N=6,478) IPAH (N=1,189) Sarcoidosis (N=756) 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 comparisons All comparisons with Alpha-1 and CF are statistically significant at < 0.01 COPD vs. IPF: p < 0.0001

ISHLT

2011

J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132

Single vs Double Lung Transplant

Single Lung Single Lung

ADULT LUNG TRANSPLANTATION

Kaplan-Meier Survival (Transplants: January 1994 - June 2009)

20 40 60 80 100 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Years

Bilateral/Double Lung (N=16,628) Single Lung (N=12,085) All Lungs (N= 28,727) Double lung: 1/2-life = 6.8 Years; Single lung: 1/2-life = 4.7 Years All lungs: 1/2-life = 5.5 Years

P < 0.0001 Survival (%)

ISHLT

2011

J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132

Optimizing Supply : Demand Ratio

• Recipient selection

criteria:

– Age – Diagnosis – Single vs double lung transplant

• Donor selection criteria:
• Age
• Single vs double lung

transplant

12

5/31/2013 4

LUNG TRANSPLANTS:

Donor Age by Year of Transplant Transplants: January 1, 1987 – June 30, 2010

0% 20% 40% 60% 80% 100% 1 9 8 7 1 9 8 8 1 9 8 9 1 9 9 1 9 9 1 1 9 9 2 1 9 9 3 1 9 9 4 1 9 9 5 1 9 9 6 1 9 9 7 1 9 9 8 1 9 9 9 2 2 1 2 2 2 3 2 4 2 5 2 6 2 7 2 8 2 9 2 1 Year of Transplant 10 20 30 40 50 0-11 12-17 18-34 35-49 50-59 60+ Median Donor Age

% of transplants Median donor age (years)

ISHLT

2011

J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132

ADULT LUNG TRANSPLANTS (1/1997-6/2005)

Risk Factors for 5 Year Mortality Donor Age

0.5 1 1.5 2 15 20 25 30 35 40 45 50 55

Donor Age Relative Risk of 5 Year Mortality p = 0.0646

ISHLT

2011

J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132

Optimizing Supply : Demand Ratio

• Recipient selection

criteria:

– Age – Diagnosis – Single vs double lung transplant

• Donor selection criteria:
• Age
• Single vs double
• Rehabilitation/

reconditioning

15

Standard Lung Procurement

5/31/2013 5 “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)

5/31/2013 6

N Engl J Med 2011;364:1431-40.

From the Toronto Lung Transplant Program

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
• Gross gastric aspiration

5/31/2013 7 U.S. NOVEL Lung Trial Marginal Donor Lungs

ADULT LUNG TRANSPLANT RECIPIENTS:

Relative Incidence of Leading Causes of Death

(Deaths: January 1992 - June 2010)

ISHLT

2011

J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132 10 20 30 40 50 0-30 Days (N=2,204) 31 Days – 1 Year (N=3,781) >1 Year – 3 Years (N=3,425) >3 Years – 5 Years (N=1,962) >5 Years – 10 Years (N=2,336) >10 Years (N=675) Bronchiolitis Malignancy (non-Lymph/PTLD) Infection (non-CMV) Graft Failure Cardiovascular

Percentage of Deaths

OCS INSPIRE Trial International Randomized Trial

Goals: To compare the safety and effectiveness of the OCS Lung compared to cold storage for donor lung preservation Design: A prospective, international, multi- center, randomized controlled trial comparing preservation of donor lungs using OCS-Lung perfusion device (Treatment Group) to cold flush and storage (Control Group) Size: Up-to 20 participating sites with up to 264 randomized male and female subjects who are primary lung transplant recipients.

5/31/2013 8

OCS™ Lung Technology

The ONLY Portable, Integrated and Automated Perfusion & Ventilation System

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

INSPIRE Trial Centers To-Date

Hannover Berlin Madrid Padua Leuven Strasbourg Bichat Harefield Leuven

EU Sites

Cleveland Clinic UCLA UPMC The Methodist UCSF

US Sites

Sydney

Australia

Edmonton

Canada

Early Clinical Experience

• OCS Lung was released in the European market

in Jan 2011

• Between February-July 2011, 13 double lung

transplant procedures on the OCS™-Lung device

• Non-randomized and were consecutive case

series at Hannover Medical School, Hannover, Germany and Puerta de Hierro Majdahonda Hospital, Madrid, Spain

5/31/2013 9

The INSPIRE International Lung Trial With The Organ Care System Technology (OCS™)

• G. Warnecke, A. Haverich, G. Massard, N. Santelmo, F. Rea, C. Knosalla, R. Hetzer,
• G. Leseche, A. Ardehali, A. R. Simon, J. Kukreja, K. McCurrey

Early outcome

Post transplant outcomes OCS (N=9) SOC (N=10) ICU time (hours) Mean +/- SD 170+/-350 97+/-91 Median 50 65 Range 15 - 1033 16 - 276 Mechanical ventilation time (hours) Mean +/- SD 14.4+/-5.5 15.5+/-5.6 Median 14.5 15.0 Range 5 - 22 9 - 27 Survival at 30 days Patient [n(%)] 6 (100) 7 (100) 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

35

Thank You !