Dosing Regimen of Eculizumab Added to Conventional Treatment in Positive Cross Match Living Donor Kidney Transplant
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00670774|
Recruitment Status : Completed
First Posted : May 2, 2008
Results First Posted : June 25, 2018
Last Update Posted : June 25, 2018
A strongly positive crossmatch has long been considered an absolute contraindication to kidney transplantation and most patients with anti-human leukocyte antigen (HLA) antibody never were able to receive a kidney transplant. Over the past decade, significant progress has been made in overcoming early antibody-mediated renal allograft injury. Our group has performed more than 200 such transplants providing the possibility of transplant to previously untransplantable patients. Despite our best efforts, transplantation in these patients is still complicated by a high rate of acute humoral rejection (AHR).
Patients included in this study will be those who have demonstrable anti-HLA antibody specific for their living donor. It is our hypothesis that blockade of terminal complement activation at the time of transplant in combination with our current protocols will reduce the incidence of AHR in patients with anti-donor HLA antibody.
|Condition or disease||Intervention/treatment||Phase|
|Kidney Transplant||Drug: Eculizumab||Phase 1 Phase 2|
The eculizumab dosing regimen was modified from that used in the treatment of paroxysmal nocturnal hemoglobinuria and consisted of 1200 mg immediately prior to transplantation, 600 mg on postoperative day 1, and 600 mg weekly thereafter for 4 weeks. At week 4, assessment of DSA levels was performed. Eculizumab was discontinued in patients whose DSA had significantly decreased (B flow crossmatch channel shift<200). In patients with persistently high DSA and thus believed to have continued high risk for AMR, eculizumab treatment continued (1200 mg week 5, and then every 2 weeks). Another DSA assessment was performed at week 9 and eculizumab was discontinued if the B flow crossmatch channel shift was <200.
The eculizumab group were compared to a historical control group consisting of consecutive transplants between 1/1/2005 and 1/10/2017 who met the inclusion criteria. The historical control group had been treated with a similar plasma exchange based protocol without eculizumab.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||31 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Single Center, Open-label Study to Determine the Safety and Efficacy of a Dosing Regimen of Eculizumab Added to Conventional Treatment in the Prevention of Antibody-mediated Rejection (AMR) in Positive Crossmatch Living Donor Kidney Transplantation|
|Actual Study Start Date :||March 2008|
|Actual Primary Completion Date :||May 2017|
|Actual Study Completion Date :||August 2017|
Patients received eculizumab intravenously according to details provided in the intervention description.
Other Name: Soliris
- Number of Subjects With Antibody-Mediated Rejection (AMR) in the First 3 Months After Living Donor Kidney Transplantation [ Time Frame: up to 3 months ]AMR can cause acute graft loss or shorten allograft survival. Renal allograft biopsies were obtained percutaneously using ultrasound guidance processed for light microscopy and immunofluorescence for peritubular capillary staining for C4d. All biopsies were reviewed by a pathologist in a blinded fashion. AMR was diagnosed using standard Banff criteria in combination with graft dysfunction (increase in serum creatinine >/=0.3 mg/dL over nadir.)
- Number of Patients Developing High DSA Levels at Less Than or Equal to 3 Months [ Time Frame: 3 months ]High DSA levels were defined as B flow cross match channel shift >350 at any time point in the first 3 months.
- Number of Patients Requiring Splenectomy [ Time Frame: 1 year ]A splenectomy is a surgical operation involving removal of the spleen. Splenectomy was performed for severe AMR in the setting of a rising serum creatinine (usually >2.0) and a rising serum DSA level despite daily plasma exchange treatments.
- Graft Dysfunction in First Month Post Transplant [ Time Frame: 1 month ](Maximum serum creatinine-nadir serum creatinine)
- Length of Follow-up [ Time Frame: up to 15 months ]Following the completion of dosing, subjects were to return for follow-up visits at 3 and 6 months post transplant to obtain biopsies and collect follow-up data. Subjects who continued the drug for 12 months were to receive their final assessment at 15 months.
- Number of Subjects With Graft Survival at One Year [ Time Frame: 1 year ]Graft survival means the kidney has not been rejected by the body.
- Number of Subjects Receiving Posttransplant Plasma Exchange (PE) [ Time Frame: up to one year ]Plasma exchange is needed when there is poor kidney functioning, and donor specific alloantibody (DSA) is high
- Transplant Glomerulopathy Incidence at One Year [ Time Frame: 1 year ]Transplant glomerulopathy is a morphologic lesion of renal allografts that is characterized histologically by duplication and/or multilayering of the glomerular basement membrane. It is widely accepted as a manifestation of chronic antibody-mediated rejection (AMR). This is determined by histology.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00670774
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Mark D. Stegall, M.D.||Mayo Clinic|