Donor Dopamine and Initial Graft Function

Kidney Transplantation Clinical Trial

Official title:

Prospective Randomized Trial to Evaluate the Efficacy of Donor Preconditioning With Dopamine on Initial Graft Function After Kidney Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00115115
• Other study ID #: 3074_KAC03.wpd
• Status: Completed
• Phase: Phase 4
• First received: June 20, 2005
• Last updated: April 22, 2009
• Start date: March 2004
• Est. completion date: March 2009

Study information

• Verified date: April 2009
• Source: Universitätsmedizin Mannheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

Donor pre-treatment with dopamine reduces injury to the kidney graft with consequences on the clinical performance immediately after transplantation: Donor dopamine reduces the requirement of dialysis post transplant, and results in renal function improvements.

The purpose of the study is to investigate the potentially therapeutic impact of donor preconditioning with low dose dopamine in human renal transplant recipients from a brain dead donor.

Description:

During the transplantation process, the kidney graft is exposed to numerous events which may in turn lead to function deteriorations. In particular, factors related with brain death, like hemodynamic instability and systemic release of cytokines, cold preservation upon harvesting, and reperfusion injury accumulate in harm conveying a pro-inflammatory state to the graft before transplantation. Early graft dysfunction has long-term consequences. Renal transplants with delayed graft function and acute rejection have a greater incidence of chronic dysfunction. Allorecognition is induced when the host immune system detects alloantigens in the context of danger signals. Reducing danger signals through medical donor management may therefore have a considerable impact on the transplantation outcomes.

In a case control study from the Transplantation Center of Mannheim, Germany, donor use of both dopamine and noradrenaline during intensive care before organ retrieval was associated with less acute rejection episodes after transplantation and resulted in superior long-term graft survival. Donor employment of catecholamines remained predictive of an improved graft survival probability even after controlling for various confounding factors like age, gender, cold ischemia, HLA matching and immunosuppressive medication. This observation has been confirmed by a larger retrospective cohort study based on the Eurotransplant registry, including 2404 kidney transplants performed at 47 renal transplantation centers in 1993. The salutary effect on the graft function rate at 4 years exhibited a dose-response relationship and compared in quantitative terms with prospective HLA matching on class I or II antigens. Besides these long-term benefits, donor preconditioning with dopamine is associated with improvements of immediate graft function after kidney transplantation. Donor dopamine was associated with less requirement of hemodialysis and more rapid recovery of graft function posttransplant in a single centre study involving 254 consecutive renal transplant recipients.

Implementing dopamine as a therapeutic tool in the management of cadaver kidney donors may have a major impact on both immediate graft function and long-term graft survival without adverse side effects for the recipients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 487
• Est. completion date: March 2009
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Donors:

• Brain death confirmed

• Given consent to organ donation

• Current s-creatinine < 2mg/dl

• On admission s-creatinine < 1.3mg/dl

Recipients:

• Age over 18 years

• Placed on the waiting list

• Organ allocation according to ET standards

Exclusion Criteria:

Donors:

• Application of dopamine/dobutamine/adrenaline

• Application of noradrenaline > 0.4µg/kg*min

• Hemodynamic instability

Recipients:

• Refusal to participate in study /data analysis

• Pregnancy

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• ESRD
• Kidney Transplantation

Intervention

Drug:
• Dopamine infusion to brain dead organ donors
Dopamine infusion administered at a dosage of 4µg/kg/min starting after brain death has been proven until to surgical procurement of the kidneys

Locations

Country	Name	City	State
Germany	University Hospital Mannheim	Mannheim	Baden-Wuerttemberg

Sponsors (5)

Lead Sponsor	Collaborator
Universitätsmedizin Mannheim	Eurotransplant International Foundation, Leiden, The Netherlands, Novartis, Regional Organ Procurement Organization (DSO), Baden-Wuerttemberg, Germany, Regional Organ Procurement Organization (DSO), Bavaria, Germany

Country where clinical trial is conducted

Germany, 

References & Publications (4)

Schnuelle P, Berger S, de Boer J, Persijn G, van der Woude FJ. Effects of catecholamine application to brain-dead donors on graft survival in solid organ transplantation. Transplantation. 2001 Aug 15;72(3):455-63. — View Citation

Schnuelle P, Lorenz D, Mueller A, Trede M, Van Der Woude FJ. Donor catecholamine use reduces acute allograft rejection and improves graft survival after cadaveric renal transplantation. Kidney Int. 1999 Aug;56(2):738-46. — View Citation

Schnuelle P, Yard BA, Braun C, Dominguez-Fernandez E, Schaub M, Birck R, Sturm J, Post S, van der Woude FJ. Impact of donor dopamine on immediate graft function after kidney transplantation. Am J Transplant. 2004 Mar;4(3):419-26. — View Citation

Yard B, Beck G, Schnuelle P, Braun C, Schaub M, Bechtler M, Göttmann U, Xiao Y, Breedijk A, Wandschneider S, Lösel R, Sponer G, Wehling M, van der Woude FJ. Prevention of cold-preservation injury of cultured endothelial cells by catecholamines and related compounds. Am J Transplant. 2004 Jan;4(1):22-30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Requirement of hemodialysis post-transplant		within 1 week after surgery	No
Secondary	Incidence and severity of acute rejection episodes		within the first 30 days (plus minus 3 days) after surgery	No
Secondary	S-creatinine on days 1-7 post transplant		within the first week after transplantation	No
Secondary	Patient and graft survival		after 12, 24 and 36 months post-transplant	No