Donor Dopamine and Initial Graft Function

NCT ID: NCT00115115

Last Updated: 2009-04-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 487 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-03-31
• Study Completion Date: 2009-03-31

Brief 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.

Detailed 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.

Conditions

Kidney Transplantation; ESRD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eurotransplant International Foundation, Leiden, The Netherlands

OTHER

Sponsor Role: collaborator

Regional Organ Procurement Organization (DSO), Baden-Wuerttemberg, Germany

OTHER

Sponsor Role: collaborator

Regional Organ Procurement Organization (DSO), Bavaria, Germany

OTHER

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: collaborator

Universitätsmedizin Mannheim

OTHER

Sponsor Role: lead

Responsible Party

University Hospital Mannheim, Dept. of Medicine V, Theodor Kutzer Ufer 1-3, 68135 Mannheim, Germany

Principal Investigators

Peter Schnuelle, MD

Role: PRINCIPAL_INVESTIGATOR

Universitätsmedizin Mannheim

Fokko J van der Woude, MD, PhD

Role: STUDY_CHAIR

Universitätsmedizin Mannheim

Werner Lauchart, MD

Role: STUDY_DIRECTOR

Organ procurement organization (DSO) of Baden-Wuerttemberg

Detlef Boesebeck, MD

Role: STUDY_DIRECTOR

Organ procurement organization (DSO) of Bavaria

Locations

University Hospital Mannheim

Mannheim, Baden-Wurttemberg, Germany

Countries

Germany

References

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. doi: 10.1111/j.1600-6143.2004.00331.x.

Reference Type: BACKGROUND

PMID: 14961996 (View on PubMed)

Yard B, Beck G, Schnuelle P, Braun C, Schaub M, Bechtler M, Gottmann U, Xiao Y, Breedijk A, Wandschneider S, Losel 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. doi: 10.1046/j.1600-6143.2003.00268.x.

Reference Type: BACKGROUND

PMID: 14678031 (View on PubMed)

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. doi: 10.1097/00007890-200108150-00017.

Reference Type: BACKGROUND

PMID: 11502976 (View on PubMed)

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. doi: 10.1046/j.1523-1755.1999.00567.x.

Reference Type: BACKGROUND

PMID: 10432416 (View on PubMed)

Benck U, Jung M, Kruger B, Grimm A, Weiss C, Yard BA, Lehner F, Kiessling A, Fischer L, Gallinat A, Kleespies A, Lorf T, Sucher R, Monch C, Scherer MN, Rahmel A, Schemmer P, Kramer BK, Schnuelle P. Donor Dopamine Does Not Affect Liver Graft Survival: Evidence of Safety From a Randomized Controlled Trial. Liver Transpl. 2018 Oct;24(10):1336-1345. doi: 10.1002/lt.25301.

Reference Type: DERIVED

PMID: 30102825 (View on PubMed)

Schnuelle P, Benck U, Kramer BK, Yard BA, Zuckermann A, Wagner F, Szabo G, Borggrefe M, Karck M, Gummert J. Impact of Donor Core Body Temperature on Graft Survival After Heart Transplantation. Transplantation. 2018 Nov;102(11):1891-1900. doi: 10.1097/TP.0000000000002337.

Reference Type: DERIVED

PMID: 29994980 (View on PubMed)

Schnuelle P, Mundt HM, Druschler F, Schmitt WH, Yard BA, Kramer BK, Benck U. Impact of spontaneous donor hypothermia on graft outcomes after kidney transplantation. Am J Transplant. 2018 Mar;18(3):704-714. doi: 10.1111/ajt.14541. Epub 2017 Nov 22.

Reference Type: DERIVED

PMID: 29027352 (View on PubMed)

Schnuelle P, Schmitt WH, Weiss C, Habicht A, Renders L, Zeier M, Druschler F, Heller K, Pisarski P, Banas B, Kramer BK, Jung M, Lopau K, Olbricht CJ, Weihprecht H, Schenker P, De Fijter JW, Yard BA, Benck U. Effects of Dopamine Donor Pretreatment on Graft Survival after Kidney Transplantation: A Randomized Trial. Clin J Am Soc Nephrol. 2017 Mar 7;12(3):493-501. doi: 10.2215/CJN.07600716. Epub 2017 Feb 17.

Reference Type: DERIVED

PMID: 28213388 (View on PubMed)

Benck U, Gottmann U, Hoeger S, Lammert A, Rose D, Boesebeck D, Lauchart W, Birck R, Weiss C, Kramer BK, Yard BA, Schnuelle P. Donor desmopressin is associated with superior graft survival after kidney transplantation. Transplantation. 2011 Dec 15;92(11):1252-8. doi: 10.1097/TP.0b013e318236cd4c.

Reference Type: DERIVED

PMID: 22067309 (View on PubMed)

Benck U, Hoeger S, Brinkkoetter PT, Gottmann U, Doenmez D, Boesebeck D, Lauchart W, Gummert J, Karck M, Lehmkuhl HB, Bittner HB, Zuckermann A, Wagner F, Schulz U, Koch A, Bigdeli AK, Bara C, Hirt S, Berchtold-Herz M, Brose S, Herold U, Boehm J, Welp H, Strecker T, Doesch A, Birck R, Kramer BK, Yard BA, Schnuelle P. Effects of donor pre-treatment with dopamine on survival after heart transplantation: a cohort study of heart transplant recipients nested in a randomized controlled multicenter trial. J Am Coll Cardiol. 2011 Oct 18;58(17):1768-77. doi: 10.1016/j.jacc.2011.05.060.

Reference Type: DERIVED

PMID: 21996389 (View on PubMed)

Schnuelle P, Gottmann U, Hoeger S, Boesebeck D, Lauchart W, Weiss C, Fischereder M, Jauch KW, Heemann U, Zeier M, Hugo C, Pisarski P, Kramer BK, Lopau K, Rahmel A, Benck U, Birck R, Yard BA. Effects of donor pretreatment with dopamine on graft function after kidney transplantation: a randomized controlled trial. JAMA. 2009 Sep 9;302(10):1067-75. doi: 10.1001/jama.2009.1310.

Reference Type: DERIVED

PMID: 19738091 (View on PubMed)

Other Identifiers

3074_KAC03.wpd

Identifier Type: -

Identifier Source: org_study_id