Donor Dopamine and Initial Graft Function

This study has been completed.
Sponsor:
Collaborators:
Eurotransplant International Foundation, Leiden, The Netherlands
Regional Organ Procurement Organization (DSO), Baden-Wuerttemberg, Germany
Regional Organ Procurement Organization (DSO), Bavaria, Germany
Novartis
Information provided by:
Universitätsmedizin Mannheim
ClinicalTrials.gov Identifier:
NCT00115115
First received: June 20, 2005
Last updated: April 22, 2009
Last verified: April 2009
  Purpose

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.


Condition Intervention Phase
Kidney Transplantation
ESRD
Drug: Dopamine infusion to brain dead organ donors
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospective Randomized Trial to Evaluate the Efficacy of Donor Preconditioning With Dopamine on Initial Graft Function After Kidney Transplantation

Resource links provided by NLM:


Further study details as provided by Universitätsmedizin Mannheim:

Primary Outcome Measures:
  • Requirement of hemodialysis post-transplant [ Time Frame: within 1 week after surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence and severity of acute rejection episodes [ Time Frame: within the first 30 days (plus minus 3 days) after surgery ] [ Designated as safety issue: No ]
  • S-creatinine on days 1-7 post transplant [ Time Frame: within the first week after transplantation ] [ Designated as safety issue: No ]
  • Patient and graft survival [ Time Frame: after 12, 24 and 36 months post-transplant ] [ Designated as safety issue: No ]

Enrollment: 487
Study Start Date: March 2004
Study Completion Date: March 2009
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    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
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00115115

Locations
Germany
University Hospital Mannheim
Mannheim, Baden-Wuerttemberg, Germany, 68135
Sponsors and Collaborators
Universitätsmedizin Mannheim
Eurotransplant International Foundation, Leiden, The Netherlands
Regional Organ Procurement Organization (DSO), Baden-Wuerttemberg, Germany
Regional Organ Procurement Organization (DSO), Bavaria, Germany
Novartis
Investigators
Principal Investigator: Peter Schnuelle, MD Universitätsmedizin Mannheim
Study Chair: Fokko J van der Woude, MD, PhD Universitätsmedizin Mannheim
Study Director: Werner Lauchart, MD Organ procurement organization (DSO) of Baden-Wuerttemberg
Study Director: Detlef Boesebeck, MD Organ procurement organization (DSO) of Bavaria
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Peter Schnuelle, MD, University Hospital Mannheim, Dept. of Medicine V, Theodor Kutzer Ufer 1-3, 68135 Mannheim, Germany
ClinicalTrials.gov Identifier: NCT00115115     History of Changes
Other Study ID Numbers: 3074_KAC03.wpd
Study First Received: June 20, 2005
Last Updated: April 22, 2009
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Universitätsmedizin Mannheim:
Donor dopamine
Immediate graft function
Kidney transplantation

Additional relevant MeSH terms:
Dopamine
Dopamine Agents
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents

ClinicalTrials.gov processed this record on July 24, 2014