Functional Antigen Matching in Corneal Transplantation - Full Text View

Sponsors and Collaborators:	University Hospital Freiburg German Research Foundation
Information provided by:	University Hospital Freiburg
ClinicalTrials.gov Identifier:	NCT00810472

Purpose

Penetrating keratoplasty is one of the most commonly performed transplantation surgeries. Graft rejection is a major complication. HLA compatibility has already been demonstrated an effective prophylaxis in several retrospective investigations. The purpose of the investigators randomized clinical trial is to demonstrate superiority of HLA matching in comparison to random graft assignment with respect to the endpoint 'time to first endothelial graft rejection' in penetrating keratoplasty. The investigators will perform DNA-based allele resolution typing.

Condition	Intervention
Corneal Diseases	Other: HLA Matching Procedure: Penetrating keratoplasty

Study Type:	Interventional
Study Design:	Prevention, Randomized, Single Blind (Subject), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Clinical Trial to Investigate Superiority of HLA Matching in Comparison to Random Graft Assignment With Respect to the Endpoint 'Time to First Endothelial Graft Rejection' in Penetrating Keratoplasty.

Further study details as provided by University Hospital Freiburg:

Primary Outcome Measures:

Time to first endothelial graft rejection. [ Time Frame: Mostly within the first six months. ] [ Designated as safety issue: No ]

Estimated Enrollment:	650
Study Start Date:	August 2009
Estimated Study Completion Date:	April 2012
Estimated Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
HLA Matching: Experimental HLA matching is exerted by selecting the donor with least-most additional HLA alleles. We will predict the waiting time for such a donor in order to assess eligibility for the trial [8]. In addition, we will dynamically adopt the degree of matching that is aimed at depending on the predicted time interval and actual waiting time: the first donors not exerting more than 7 mismatches at the triplet-amino-acid-residue-level (HLAMatchmaker method [6]) is accepted if the patient is waiting less than half of his predicted waiting time. The next available donor exerting a 2/6 match (or better) is assigned thereafter. The next graft will be assigned, regardless of HLA matching after 6 months.	Other: HLA Matching HLA matching is exerted by selecting the donor with least-most additional HLA alleles. We will predict the waiting time for such a donor in order to assess eligibility for the trial [8]. In addition, we will dynamically adopt the degree of matching that is aimed at depending on the predicted time interval and actual waiting time: the first donors not exerting more than 7 mismatches at the triplet-amino-acid-residue-level (HLAMatchmaker method [6]) is accepted if the patient is waiting less than half of his predicted waiting time. The next available donor exerting a 2/6 match (or better) is assigned thereafter. The next graft will be assigned, regardless of HLA matching after 6 months. Procedure: Penetrating keratoplasty Corneal transplantation.
Random graft assignment: Placebo Comparator	Procedure: Penetrating keratoplasty Corneal transplantation.

Arms

Assigned Interventions

HLA Matching: Experimental

HLA matching is exerted by selecting the donor with least-most additional HLA alleles. We will predict the waiting time for such a donor in order to assess eligibility for the trial [8]. In addition, we will dynamically adopt the degree of matching that is aimed at depending on the predicted time interval and actual waiting time: the first donors not exerting more than 7 mismatches at the triplet-amino-acid-residue-level (HLAMatchmaker method [6]) is accepted if the patient is waiting less than half of his predicted waiting time.

The next available donor exerting a 2/6 match (or better) is assigned thereafter. The next graft will be assigned, regardless of HLA matching after 6 months.

Other: HLA Matching

HLA matching is exerted by selecting the donor with least-most additional HLA alleles. We will predict the waiting time for such a donor in order to assess eligibility for the trial [8]. In addition, we will dynamically adopt the degree of matching that is aimed at depending on the predicted time interval and actual waiting time: the first donors not exerting more than 7 mismatches at the triplet-amino-acid-residue-level (HLAMatchmaker method [6]) is accepted if the patient is waiting less than half of his predicted waiting time.

The next available donor exerting a 2/6 match (or better) is assigned thereafter. The next graft will be assigned, regardless of HLA matching after 6 months.

Procedure: Penetrating keratoplasty

Corneal transplantation.

Random graft assignment: Placebo Comparator

Procedure: Penetrating keratoplasty

Corneal transplantation.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Predicted waiting time for a 4/6 match lower than 6 months.

Exclusion Criteria:

Minority
Legal incapacity

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00810472

Contacts

Contact: Daniel Böhringer, MD	+49 761 270 4001	daniel.boehringer@uniklinik-freiburg.de
Contact: Daniela Goos, MD	+49 761 270 4001	daniela.goos@uniklinik-freiburg.de

Locations

Germany, Baden-Württemberg
University Eye Hospital Freiburg
Freiburg, Baden-Württemberg, Germany, 79106

Sponsors and Collaborators

University Hospital Freiburg

German Research Foundation

More Information

Publications:

Böhringer D, Spierings E, Enczmann J, Böhringer S, Sundmacher R, Goulmy E, Reinhard T. Matching of the minor histocompatibility antigen HLA-A1/H-Y may improve prognosis in corneal transplantation. Transplantation. 2006 Oct 27;82(8):1037-41.

Reinhard T, Spelsberg H, Henke L, Kontopoulos T, Enczmann J, Wernet P, Berschick P, Sundmacher R, Böhringer D. Long-term results of allogeneic penetrating limbo-keratoplasty in total limbal stem cell deficiency. Ophthalmology. 2004 Apr;111(4):775-82.

Reinhard T, Böhringer D, Enczmann J, Kögler G, Mayweg S, Wernet P, Sundmacher R. Improvement of graft prognosis in penetrating normal-risk keratoplasty by HLA class I and II matching. Eye. 2004 Mar;18(3):269-77.

Böhringer D, Reinhard T, Duquesnoy RJ, Böhringer S, Enczmann J, Lange P, Claas F, Sundmacher R. Beneficial effect of matching at the HLA-A and -B amino-acid triplet level on rejection-free clear graft survival in penetrating keratoplasty. Transplantation. 2004 Feb 15;77(3):417-21.

Reinhard T, Böhringer D, Enczmann J, Kögler G, Wernet P, Böhringer S, Sundmacher R. HLA class I/II matching and chronic endothelial cell loss in penetrating normal risk keratoplasty. Acta Ophthalmol Scand. 2004 Feb;82(1):13-8.

Böhringer D, Reinhard T, Enczmann J, Godehard E, Sundmacher R. Individual analysis of expected time on the waiting list for HLA-matched corneal grafts. Dev Ophthalmol. 2003;36:50-5.

Responsible Party:	University Eye Hospital Freiburg ( Daniel Böhringer )
Study ID Numbers:	FR-2008-FANCY
Study First Received:	December 17, 2008
Last Updated:	July 21, 2009
ClinicalTrials.gov Identifier:	NCT00810472 History of Changes
Health Authority:	Germany: Ethics Commission

Keywords provided by University Hospital Freiburg:

Penetrating keratoplasty
HLA matching
Corneal diseases that require penetrating keratoplasty

Study placed in the following topic categories:

Corneal Diseases
Eye Diseases

Additional relevant MeSH terms:

Corneal Diseases
Eye Diseases

ClinicalTrials.gov processed this record on September 03, 2009