NCT00810472

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
650

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Sep 2009

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 17, 2008

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 18, 2008

Completed
9 months until next milestone

Study Start

First participant enrolled

September 1, 2009

Completed
5.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2015

Completed
Last Updated

October 25, 2016

Status Verified

October 1, 2016

Enrollment Period

5.7 years

First QC Date

December 17, 2008

Last Update Submit

October 24, 2016

Conditions

Corneal Diseases

Keywords

Penetrating keratoplastyHLA matchingCorneal diseases that require penetrating keratoplasty

Outcome Measures

Primary Outcomes (1)

  • Time to first endothelial graft rejection.

    Mostly within the first six months.

Study Arms (2)

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 MatchingProcedure: Penetrating keratoplasty

Random graft assignment

PLACEBO COMPARATOR
Procedure: Penetrating keratoplasty

Interventions

HLA MatchingOTHER

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.

HLA Matching
Penetrating keratoplastyPROCEDURE

Corneal transplantation.

HLA MatchingRandom graft assignment

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • Minority
  • Legal incapacity

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Eye Hospital Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Related Publications (8)

  • Bohringer D, Spierings E, Enczmann J, Bohringer 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. doi: 10.1097/01.tp.0000235908.54766.44.

    PMID: 17060851BACKGROUND

  • Reinhard T, Spelsberg H, Henke L, Kontopoulos T, Enczmann J, Wernet P, Berschick P, Sundmacher R, Bohringer D. Long-term results of allogeneic penetrating limbo-keratoplasty in total limbal stem cell deficiency. Ophthalmology. 2004 Apr;111(4):775-82. doi: 10.1016/j.ophtha.2003.07.013.

    PMID: 15051212BACKGROUND

  • Reinhard T, Bohringer D, Enczmann J, Kogler G, Mayweg S, Wernet P, Sundmacher R. Improvement of graft prognosis in penetrating normal-risk keratoplasty by HLA class I and II matching. Eye (Lond). 2004 Mar;18(3):269-77. doi: 10.1038/sj.eye.6700636.

    PMID: 15004576BACKGROUND

  • Bohringer D, Reinhard T, Duquesnoy RJ, Bohringer 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. doi: 10.1097/01.TP.0000110415.10401.94.

    PMID: 14966417BACKGROUND

  • Reinhard T, Bohringer D, Enczmann J, Kogler G, Wernet P, Bohringer 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. doi: 10.1046/j.1600-0420.2003.00188.x.

    PMID: 14738484BACKGROUND

  • Bohringer 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. doi: 10.1159/000067648.

    PMID: 12494680BACKGROUND

  • Bohringer D, Grotejohann B, Ihorst G, Reinshagen H, Spierings E, Reinhard T. Rejection Prophylaxis in Corneal Transplant. Dtsch Arztebl Int. 2018 Apr 13;115(15):259-265. doi: 10.3238/arztebl.2018.0259.

    PMID: 29735006DERIVED

  • Bohringer D, Ihorst G, Grotejohann B, Maurer J, Spierings E, Reinhard T; FANCY study group. Functional antigen matching in corneal transplantation: matching for the HLA-A, -B and -DRB1 antigens (FANCY) - study protocol. BMC Ophthalmol. 2014 Dec 13;14:156. doi: 10.1186/1471-2415-14-156.

    PMID: 25496165DERIVED

MeSH Terms

Conditions

Corneal Diseases

Interventions

Keratoplasty, Penetrating

Condition Hierarchy (Ancestors)

Eye Diseases

Intervention Hierarchy (Ancestors)

Corneal TransplantationTissue TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsRefractive Surgical ProceduresOphthalmologic Surgical ProceduresSurgical Procedures, OperativeTransplantation

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Apl.Prof.Dr.med.

Study Record Dates

First Submitted

December 17, 2008

First Posted

December 18, 2008

Study Start

September 1, 2009

Primary Completion

May 1, 2015

Study Completion

May 1, 2015

Last Updated

October 25, 2016

Record last verified: 2016-10

Locations

DE(1)