Optimization of Donor-Recipient Matching in Lung Transplantation

NCT05195853 | Unknown

• 1 other identifier: ADRTP
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Lung transplantation is the curative treatment for end-stage respiratory failure involving highly selected patients. In 2018, the International Transplant Registry counts 69200 lung transplants among 260 transplant centers. Between 2010 and June 2017, the 3-month survival rate of patients after lung transplantation is 90%. The causes of early death are primary graft failure, renal failure, infections, acute rejection (cellular or humoral), surgical complications. The median survival is 6.7 years and the median conditioned survival at 1 year is 8.9 years. Bronchiolitis obliterans is the leading cause of death after 1 year; it affects 10% more patients each year and peaks at 5 years at more than 50% of transplanted patients. These results encourage transplant professionals to continue their efforts to improve the prognosis of transplantation. Among these, the optimization of graft matching, taking into account the characteristics of the donor and the recipient, constitute a relevant avenue of study. Several donor characteristics seem to play a role in the prognosis of the transplant. Survival at 12 months is significantly worse when the donor's age is greater than 50 years. There does not appear to be a significant difference in donor cause of death. Recipients of a graft exposed to smoking ≥ 20 pack-years have a 3% and 1.5% decreased survival at 1 and 5 years postoperatively. Similarly, the 5-year survival of patients with conditional 1-year survival is poorer in case of other toxic exposures such as alcohol, cocaine, crack or marijuana. Analysis of international registry data also suggests a negative association between post-transplant survival and donor hypertension and diabetes. However, the biological mechanisms by which these factors affect survival remain unknown. Graft ischemia time is significantly associated with survival with a 5-year survival of 70% and 65% for grafts exposed to ischemia ≥ 4 hours or less. The cumulative effect of donor hypertension and ischemia time are appreciated by the fact that the best postoperative survival is observed in donors without hypertension and graft ischemia time ≥ 4 hours. Graft size is also associated with post-transplant prognosis, in front of a significant decrease in survival for patients with emphysema, chronic obstructive pulmonary disease, alpha-1 antitrypsin deficiency, transplanted with a smaller graft size. This result is not found in patients transplanted for pulmonary fibrosis. One study has also suggested the negative role of a gender mismatch between donor and recipient on post-transplant survival, but there is currently no clear explanation for this result. The presence of antibodies to the recipient's HLA system \[DSA (donor-specific antibodies)\] in pre-transplant is a risk factor for hyperacute rejection and chronic graft dysfunction. Thus, the choice of matching between the donor and the recipient appears complex in view of the number of criteria to be taken into account which impact the duration of post-transplant survival in the short and medium term. The objective of the project is to develop a decision support tool, using artificial intelligence algorithms, to assist the thoracic surgeon in identifying the patient, among those registered on the team's waiting list, who could benefit most from a bi-pulmonary graft offered by the Biomedicine Agency.

Conditions

Lung Transplant

Outcome Measures

Primary Outcomes (1)

• Construction of a tool to predict 90-day survival of patients managed for bi-pulmonary transplantation

  This outcome corresponds to the number of all-cause deaths within 90 days of transplantation. Deaths occurring during hospitalization or at home are taken into account

  Day 90

Secondary Outcomes (4)

• Prediction of the risk of a complication during the transplant hospital stay

  Day 90

• Number of hospitalization at Year 1

  Year 1

• Number of rejection of the transplant at Year 1

  Year 1

• Respiratory functional benefit in the year following transplantation

  Year 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

These patients were admitted for a bi-lung transplant performed by the Marie Lannelongue lung transplant team between January 1, 2007 and April 30, 2021.

You may qualify if:

• Patients who have received a bi-lung transplant performed by the Marie Lannelongue lung transplant team between January 1, 2007 and April 30, 2021 All indications for transplantation will be considered, including retransplantation.
• French-speaking patient

You may not qualify if:

• Patient is a minor (\<18 years old) at the time of transplantation
• Patient's refusal to participate in the study
• Patient under guardianship or curatorship
• Patient deprived of liberty
• Patient under court protection
• Patient objecting to the use of his/her data for this research

Sponsors & Collaborators

• Fondation Hôpital Saint-Joseph: lead

Study Sites (1)

Groupe Hospitalier Paris Saint-Joseph

Paris, 75014, France

RECRUITING

Related Publications (8)

• Leard LE, Holm AM, Valapour M, Glanville AR, Attawar S, Aversa M, Campos SV, Christon LM, Cypel M, Dellgren G, Hartwig MG, Kapnadak SG, Kolaitis NA, Kotloff RM, Patterson CM, Shlobin OA, Smith PJ, Sole A, Solomon M, Weill D, Wijsenbeek MS, Willemse BWM, Arcasoy SM, Ramos KJ. Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2021 Nov;40(11):1349-1379. doi: 10.1016/j.healun.2021.07.005. Epub 2021 Jul 24.

  PMID: 34419372 BACKGROUND

• Chambers DC, Cherikh WS, Harhay MO, Hayes D Jr, Hsich E, Khush KK, Meiser B, Potena L, Rossano JW, Toll AE, Singh TP, Sadavarte A, Zuckermann A, Stehlik J; International Society for Heart and Lung Transplantation. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-sixth adult lung and heart-lung transplantation Report-2019; Focus theme: Donor and recipient size match. J Heart Lung Transplant. 2019 Oct;38(10):1042-1055. doi: 10.1016/j.healun.2019.08.001. Epub 2019 Aug 8. No abstract available.

  PMID: 31548030 BACKGROUND

• Chambers DC, Zuckermann A, Cherikh WS, Harhay MO, Hayes D Jr, Hsich E, Khush KK, Potena L, Sadavarte A, Singh TP, Stehlik J; International Society for Heart and Lung Transplantation. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: 37th adult lung transplantation report - 2020; focus on deceased donor characteristics. J Heart Lung Transplant. 2020 Oct;39(10):1016-1027. doi: 10.1016/j.healun.2020.07.009. Epub 2020 Jul 30. No abstract available.

  PMID: 32782073 BACKGROUND

• Demir A, Coosemans W, Decaluwe H, De Leyn P, Nafteux P, Van Veer H, Verleden GM, Van Raemdonck D. Donor-recipient matching in lung transplantation: which variables are important?dagger. Eur J Cardiothorac Surg. 2015 Jun;47(6):974-83. doi: 10.1093/ejcts/ezu340. Epub 2014 Sep 3.

  PMID: 25187532 BACKGROUND

• Frost AE, Jammal CT, Cagle PT. Hyperacute rejection following lung transplantation. Chest. 1996 Aug;110(2):559-62. doi: 10.1378/chest.110.2.559.

  PMID: 8697867 BACKGROUND

• Brugiere O, Suberbielle C, Thabut G, Lhuillier E, Dauriat G, Metivier AC, Gautreau C, Charron D, Mal H, Parquin F, Stern M. Lung transplantation in patients with pretransplantation donor-specific antibodies detected by Luminex assay. Transplantation. 2013 Mar 15;95(5):761-5. doi: 10.1097/TP.0b013e31827afb0f.

  PMID: 23296148 BACKGROUND

• Snell GI, Yusen RD, Weill D, Strueber M, Garrity E, Reed A, Pelaez A, Whelan TP, Perch M, Bag R, Budev M, Corris PA, Crespo MM, Witt C, Cantu E, Christie JD. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction, part I: Definition and grading-A 2016 Consensus Group statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2017 Oct;36(10):1097-1103. doi: 10.1016/j.healun.2017.07.021. Epub 2017 Jul 26. No abstract available.

  PMID: 28942784 BACKGROUND

• Seely AJ, Ivanovic J, Threader J, Al-Hussaini A, Al-Shehab D, Ramsay T, Gilbert S, Maziak DE, Shamji FM, Sundaresan RS. Systematic classification of morbidity and mortality after thoracic surgery. Ann Thorac Surg. 2010 Sep;90(3):936-42; discussion 942. doi: 10.1016/j.athoracsur.2010.05.014.

  PMID: 20732521 BACKGROUND

Study Officials

• Anne Buronfosse, MD

  Fondation Hôpital Saint-Joseph

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne Buronfosse, MD

CONTACT

144123873; aburonfosse@ghpsj.fr

Helene BEAUSSIER, PharmD, PhD

CONTACT

0144127883; crc@ghpsj.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 31, 2021
• First Posted: January 19, 2022
• Study Start: January 15, 2022
• Primary Completion: November 15, 2023
• Study Completion: December 31, 2023
• Last Updated: December 30, 2022

Record last verified: 2022-12

Locations

FR (1)