“Lung in a Box” No Disclosures Ex vivo Lung Perfusion (EVLP) · Program & Surgical...

5/31/2013

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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

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5/31/2013

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Supply : Demand

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Optimizing Supply : Demand Ratio

• Recipient selection criteria

– Age

– Diagnosis

– Single vs double lung

transplant

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

0

20

40

60

80

100

0 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

Su

rviv

al

(%)

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

0

12

24

36

48

60

0-11 12-17 18-34 35-4950-59 60-65 66+ Median Age

Me

dia

n r

ec

ipie

nt

ag

e (

ye

ars

)

% o

f tr

an

sp

lan

tsrs

Year of Transplant

ISHLT 2011

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

5/31/2013

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

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Years

Su

rviv

al (%

)

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)

0

20

40

60

80

100

0 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

Su

rviv

al (%

)

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

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LUNG TRANSPLANTS: Donor 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

Year of Transplant

0

10

20

30

40

50

0-11 12-17 18-34 35-49 50-59 60+ Median Donor Age

% o

f tr

an

sp

lan

ts

Me

dia

n d

on

or

ag

e (

ye

ars

)

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

0.5

1

1.5

2

15 20 25 30 35 40 45 50 55

Donor Age

Re

lati

ve

Ris

k o

f 5

Yea

r M

ort

ality

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

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Standard Lung Procurement

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“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)

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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

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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

0

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

Perc

en

tag

e o

f D

ea

ths

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.

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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

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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

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Thank You !