Ex-Vivo Lung Perfusion to Increase the Number of Organs for Transplantation (EVLP_MI)

Ex-Vivo Lung Perfusion to Improve Donor Lung Function and Increase the Number of Organs Available for Transplantation

The recent introduction of ex-vivo lung perfusion (EVLP) as a tool to evaluate and recondition lungs from marginal donors has opened a new era in the field of lung transplantation.

Study Overview

• Status: Completed
• Conditions: Brain Death; Graft Failure; Primary Graft Dysfunction; Disorder Related to Lung Transplantation
• Intervention / Treatment: Procedure: EVLP Group

Detailed Description

Aim of the investigation: to compare the clinical outcome after transplantation of subjects receiving marginal lungs procured from brain death donors and reconditioned by EVLP, with that of subjects receiving lungs procured from standard donors.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20122
    • Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria for donor lung:

1. Recipient to undergo single or bilateral Lung Transplantation
2. Donor arterial partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) below 300 mmHg, or doubtful donor lung function

Exclusion criteria for donor lung:

1. Massive lung contusion
2. Aspiration
3. Pneumonia
4. Sepsis
5. Malignancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard Group; Recipients of lungs procured from brain death donors deemed suitable for transplantation according to standard criteria. Events: lung procurement, cold storage on ice, transplantation.
Experimental: EVLP Group; Recipients of marginal lungs procured from brain death donors and reconditioned with ex-vivo lung perfusion (EVLP). Events: lung procurement, cold storage on ice, reconditioning by EVLP, cold storage on ice, transplantation.	Procedure: EVLP Group; EVLP technique: Steen solution; normothermia; low flow, open atrium, low hematocrit. Endpoints of EVLP assessment of lungs suitability: oxygenation, respiratory mechanics, pulmonary vascular resistance, chest X-ray, fibrobronchoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Graft Dysfunction 72 hours after lung transplantation (PGD72)	Primary Graft Dysfunction 72 hours after transplantation (PGD72) definition: grade 3 according to the International Society of Heart and Lung Transplantation classification	72 hours
30 day Mortality		30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of mechanical ventilation after transplantation	30 days
ICU length of stay after transplantation	30 days

Collaborators and Investigators

• Sponsor: Policlinico Hospital
• Investigators: Principal Investigator: Franco Valenza, MD, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico Milan Italy

Publications and helpful links

General Publications

• Steen S, Ingemansson R, Eriksson L, Pierre L, Algotsson L, Wierup P, Liao Q, Eyjolfsson A, Gustafsson R, Sjoberg T. First human transplantation of a nonacceptable donor lung after reconditioning ex vivo. Ann Thorac Surg. 2007 Jun;83(6):2191-4. doi: 10.1016/j.athoracsur.2007.01.033.
• Botha P, Trivedi D, Weir CJ, Searl CP, Corris PA, Dark JH, Schueler SV. Extended donor criteria in lung transplantation: impact on organ allocation. J Thorac Cardiovasc Surg. 2006 May;131(5):1154-60. doi: 10.1016/j.jtcvs.2005.12.037.
• Cypel M, Yeung JC, Liu M, Anraku M, Chen F, Karolak W, Sato M, Laratta J, Azad S, Madonik M, Chow CW, Chaparro C, Hutcheon M, Singer LG, Slutsky AS, Yasufuku K, de Perrot M, Pierre AF, Waddell TK, Keshavjee S. Normothermic ex vivo lung perfusion in clinical lung transplantation. N Engl J Med. 2011 Apr 14;364(15):1431-40. doi: 10.1056/NEJMoa1014597.
• Oto T, Levvey BJ, Whitford H, Griffiths AP, Kotsimbos T, Williams TJ, Snell GI. Feasibility and utility of a lung donor score: correlation with early post-transplant outcomes. Ann Thorac Surg. 2007 Jan;83(1):257-63. doi: 10.1016/j.athoracsur.2006.07.040.
• Aigner C, Winkler G, Jaksch P, Seebacher G, Lang G, Taghavi S, Wisser W, Klepetko W. Extended donor criteria for lung transplantation--a clinical reality. Eur J Cardiothorac Surg. 2005 May;27(5):757-61. doi: 10.1016/j.ejcts.2005.01.024.
• Valenza F, Rosso L, Coppola S, Froio S, Colombo J, Dossi R, Fumagalli J, Salice V, Pizzocri M, Conte G, Gatti S, Santambrogio L, Gattinoni L. beta-adrenergic agonist infusion during extracorporeal lung perfusion: effects on glucose concentration in the perfusion fluid and on lung function. J Heart Lung Transplant. 2012 May;31(5):524-30. doi: 10.1016/j.healun.2012.02.001. Epub 2012 Mar 3.
• Valenza F, Rosso L, Pizzocri M, Salice V, Umbrello M, Conte G, Stanzi A, Colombo J, Gatti S, Santambrogio L, Iapichino G, Gattinoni L. The consumption of glucose during ex vivo lung perfusion correlates with lung edema. Transplant Proc. 2011 May;43(4):993-6. doi: 10.1016/j.transproceed.2011.01.122.
• Valenza F, Rosso L, Coppola S, Froio S, Palleschi A, Tosi D, Mendogni P, Salice V, Ruggeri GM, Fumagalli J, Villa A, Nosotti M, Santambrogio L, Gattinoni L. Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation. Transpl Int. 2014 Jun;27(6):553-61. doi: 10.1111/tri.12295. Epub 2014 Apr 4.

Helpful Links

• Lung transplantation

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: October 17, 2013
• First Submitted That Met QC Criteria: October 22, 2013
• First Posted (Estimate): October 23, 2013

Study Record Updates

• Last Update Posted (Estimate): October 23, 2013
• Last Update Submitted That Met QC Criteria: October 22, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Postoperative Complications; Neurologic Manifestations; Neurobehavioral Manifestations; Death; Unconsciousness; Consciousness Disorders; Coma; Reperfusion Injury; Brain Death; Primary Graft Dysfunction
• Other Study ID Numbers: EVLP_2011