Expanding Pancreas Donor Pool by Evaluation of Unallocated Organs After Brain Death - The EXPLORE Study

Unallocated Pancreas Organs Clinical Trial

Official title:

Expanding Pancreas Donor Pool by Evaluation of Unallocated Organs After Brain Death: The EXPLORE Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04127266
• Other study ID #: S-277/2019
• Status: Recruiting
• Start date: November 1, 2019
• Est. completion date: November 1, 2022

Study information

• Verified date: December 2019
• Source: University Hospital Heidelberg
• Contact: Arianeb Mehrabi, MD
• Phone: 0049 - 6221 - 5636223
• Email: arianeb.mehrabi[@]med.uni-heidelberg.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Pancreas graft quality directly affects morbidity and mortality rates after pancreas transplantation (PTx). The criteria for pancreas graft allocation are restricted, which has decreased the number of available organs. Suitable pancreatic allografts are selected based on donor demographics, medical history, and the transplant surgeon's assessment of organ quality during procurement. Quality is assessed based on macroscopic appearance, which is biased by individual experience and personal skills. Therefore, the aim of this study is to assess the histopathological quality of unallocated pancreas organs to determine how many unallocated organs are of suitable quality for PTx, based on histopathologic evaluations. The reasons for allocation rejection will be reported and the correlation between cause of allocation rejection and histopathological quality of the allocated organ will be evaluated.

This is a multicenter cross-sectional explorative study. The demographic data and medical history of donor and cause of rejection of the allocation of graft will be recorded. Organs of included donors will be explanted and macroscopic features such as weight, color, size, and stiffness will be recorded. A tissue sample of the organ will be fixed for further microscopic assessments. Histopathologic assessments will be reported 6 hours (or at time of organ delivery if later than 6 hours), 9 hours, 12 hours, 15 hours, and 18 hours after procurement. 100 pancreases will be evaluated in this study.

Description:

With advances in surgery and immunosuppressive therapy, PTx has become an accepted and standardized therapeutic surgery worldwide. Today, PTx is a promising treatment for type 1 diabetes mellitus and for patients undergoing total pancreatectomy because of benign disease. It has been demonstrated that PTx can provide a good glycemic control and insulin independence and improve diabetic lesions including retinopathy, nephropathy, neuropathy, and vasculopathy. Furthermore, thanks to improved immunosuppressive agents, prophylaxis against infections and thrombosis, and modifications in surgical approaches, outcomes after whole organ PTx has consistently improved over the past 20 years. The 1- and 5-year patient survival rates after PTx are approximately 95% and 85%, respectively, and the 1-, and 5-year graft survival rates are 90%, and 70%, respectively.

Morbidity and mortality still occurs after PTx. Morbidity and mortality rates after PTx are mainly related to pancreas graft quality. To decrease these, some restricted criteria for pancreas graft allocation have been defined. However, these allocation criteria have decreased the overall availability of pancreas organs. Consequently, despite an increase in organs from deceased donors, organ utilization (20% of all potential donor pancreases are ultimately used for whole organ transplantation) and also PTx rates (10% overall decline) have decreased. In the US, only 13% of deceased donors provide a pancreas that is utilized for transplantation. Data from Eurotransplant indicate that only 27% of donor pancreases are transplanted, either as whole pancreas grafts or as islet grafts. In addition to the restricted pancreas allocation criteria, some allocated/offered organs are not accepted by transplant surgeons (which is biased by individual experience and personal skills) after an organ quality assessment.

Longer waiting lists, increased waiting times, and donor shortages have increased the need for and number of extended donor criteria organs that are accepted for transplantation. To date, the most important selection criteria to identify suitable pancreatic allografts are donor demographics, donor medical history (age, gender, cause of death, etc.), and the transplant surgeon's own organ quality assessment based on macroscopic appearance. However, it is unclear, whether unallocated organs have a poor histopathologic quality for transplantation. To the best of our knowledge, no systematic histopathologic quality assessment of unallocated pancreas grafts has been performed, so far. In this study, for the first time, the histopathological quality of unallocated pancreas organs from brain-dead donors will be assessed to determine the number of unallocated organs that were potentially suitable for transplantation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: November 1, 2022
• Est. primary completion date: July 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 60 Years

Eligibility

Inclusion Criteria:

• Eligible brain-dead organ donors in Baden-Württemberg with consent to donation

• Pancreas reported to Eurotransplant for allocation by the German Organ Transplantation Foundation

• Age = 60 years old

• BMI = 35

Exclusion Criteria:

• Pancreases allocated for transplantation

• Pancreases allocated for islet cell transplantation after being assessed not suitable for solid organ transplantation

• History of pancreas disease

• History of pancreas surgery

Related Conditions & MeSH terms

• Brain Death
• Unallocated Pancreas Organs

Locations

Country	Name	City	State
Germany	Division of Visceral Transplantation, Department of General, Visceral and Transplantation Surgery, University of Heidelberg	Heidelberg	Baden-Württemberg

Sponsors (6)

Lead Sponsor	Collaborator
Dr. A. Mehrabi	German Organ Transplantation Foundation, Universitätsmedizin Mannheim, University Hospital Heidelberg, University Hospital Tuebingen, University of Freiburg

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Histopathological quality of pancreas	Histopathologic features of unallocated organs, including the presence of pancreatitis, fibrosis, edema, hemorragia, steatosis and fat content, dilation of pancreas ducts, and benign/malignant tumors will be reported.	18 hours
Secondary	Medical history of donors		One day
Secondary	Donor Sodium level	mmol/L	One day
Secondary	Donor Creatinine level	mg/dl	One day
Secondary	Donor Glomerular Filtration rate		One day
Secondary	Donor Serum Glucose level	mmol/L	One day
Secondary	Donor HbA1c rate		One day
Secondary	Donor Lipase level	U/l	One day
Secondary	Donor Amylase level	U/l	One day
Secondary	Pre-procurement pancreas allocation suitability score	Calculated based on age, body mass index, intensive care unit stay, duration of cardiac arrest/asystole, sodium (mmol/L), amylase (U/l), lipase (U/l), inotropic therapy [(nor)adrenaline (?) or dobuta-/dopamine (?)].	One day
Secondary	Macroscopic features of pancreas	Macroscopic features including stiffness, tissue damage, subscapular hematoma, pancreatic calcification, pancreatic edema, fatty Infiltration, and vascular status.	One day