Collaborative Corneal Transplantation Studies (CCTS)



Sponsors


Source

National Eye Institute (NEI)

Brief Summary

To determine whether histocompatibility matching of corneal transplant donors and recipients
can reduce the incidence of graft rejection in high-risk patients.

Detailed Description

Approximately 20 percent of corneal transplant patients, about 6,000 per year, face donor
tissue rejection at rates of up to 60 percent because of corneal vascularization or prior
graft rejection. Histocompatibility antigen matching and/or crossmatching may have offered
these patients an improved chance for successful outcome.

The Collaborative Corneal Transplantation Studies Group conducted two controlled,
double-masked studies addressing distinct scientific questions about donor-recipient
histocompatibility matching. The Crossmatch Study was a randomized study assessing the
effectiveness of crossmatching in preventing graft rejection among high-risk patients with
lymphocytotoxic antibodies. The Antigen Matching Study was a prospective, double-masked,
observational study of the effectiveness of HLA-A, -B, and -DR donor-recipient matching in
high-risk patients who had no lymphocytotoxic antibodies.

Six clinical centers recruited high-risk patients and collaborated with their local eye
banking and organ procurement agencies in procuring donor corneal tissue. For each of the two
studies, a total of 400 patients were sought. Blood samples from each enrolled patient were
sent to the local CCTS tissue typing laboratory for HLA typing, and serum samples were sent
to the Central Laboratory to be screened for preformed lymphocytotoxic antibodies. Depending
on the results of the testing, patients were entered into the Crossmatch Study or the Antigen
Matching Study.

As corneal donors became available, donor blood samples were HLA typed at the local
laboratories and crossmatched against all CCTS patients who awaited transplantation. Results
of the testing were entered in a national, 24-hour computerized allocation system operated by
the United Network for Organ Sharing (UNOS). Patients in the Crossmatch Study received a
cornea from either a positively crossmatched donor or a negatively crossmatched donor.
Patients in the Antigen Matching Study received a cornea with 0 to 6 matched antigens.

Transplant patients were followed intensively during the first months after surgery. The
number of clinic visits was tapered to 2 during the third and final year of followup,
resulting in a total of 17 postoperative visits. Irreversible failure of the corneal
allograft due to all causes was the primary outcome variable in both studies. Allograft
reaction episodes, irreversible failure due to rejection, and visual acuity were secondary
outcome variables.

Overall Status

Completed

Start Date

1986-05-01

Completion Date

1989-09-01

Primary Completion Date

N/A

Phase

Phase 3

Study Type

Interventional


Conditions


Intervention

Intervention Type

Procedure

Intervention Name



Eligibility

Criteria

Males and females age 10 years or older with two to four quadrants of corneal stroma
vascularization or a history of allograft rejection in the eye considered for surgery were
eligible for both studies in the CCTS.

Patients must have been willing to participate in 3 years of followup. No one was eligible
for the CCTS who had a condition that would greatly increase the risk of nonrejection graft
failure, such as xerophthalmia or severe exposure keratopathy. Also excluded were patients
with systemic diseases or with medication usage that might alter their immune response.

Gender

All

Minimum Age

10 Years

Maximum Age

N/A


Verification Date

2009-09-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Has Expanded Access

No

Firstreceived Results Date

N/A

Reference

Citation

Stark WJ, Stulting RD, Thoft R. HLA matching and corneal transplantation. N Engl J Med. 1987 Dec 3;317(23):1476-7.

PMID

3317044


Citation

Klein PK; Stark WJ; Maguire MG; Stulting RD; Collaborative Corneal Transplantation Research Group; Donor-recipient crossmatching and typing to avoid corneal allograft rejection, in Cavanaugh HD (ed)., The Cornea: The World Congress on the Cornea III, New York, Raven Press, 1988:395-398


Citation

Stark WJ, Stulting RD, Meyer RF, Foulks GN, Smith RE, Chandler JW, Maguire MG, Bias WB. Sharing tissue typing information from the collaborative corneal transplantation studies. Arch Ophthalmol. 1989 May;107(5):633.

PMID

2655566


Citation

The collaborative corneal transplantation studies (CCTS). Effectiveness of histocompatibility matching in high-risk corneal transplantation. The Collaborative Corneal Transplantation Studies Research Group. Arch Ophthalmol. 1992 Oct;110(10):1392-403.

PMID

1417537


Citation

McDonnell PJ, Enger C, Stark WJ, Stulting RD. Corneal thickness changes after high-risk penetrating keratoplasty. Collaborative Corneal Transplantation Study Group. Arch Ophthalmol. 1993 Oct;111(10):1374-81.

PMID

8216018


Citation

Fink N, Stark WJ, Maguire MG, Stulting D, Meyer R, Foulks G, Smith RE, Rapoza P. Effectiveness of histocompatibility matching in high-risk corneal transplantation: a summary of results from the Collaborative Corneal Transplantation Studies. Cesk Oftalmol. 1994 Feb;50(1):3-12.

PMID

8137435


Citation

Maguire MG, Stark WJ, Gottsch JD, Stulting RD, Sugar A, Fink NE, Schwartz A. Risk factors for corneal graft failure and rejection in the collaborative corneal transplantation studies. Collaborative Corneal Transplantation Studies Research Group. Ophthalmology. 1994 Sep;101(9):1536-47.

PMID

8090456


Citation

Hahn AB, Foulks GN, Enger C, Fink N, Stark WJ, Hopkins KA, Sanfilippo F. The association of lymphocytotoxic antibodies with corneal allograft rejection in high risk patients. The Collaborative Corneal Transplantation Studies Research Group. Transplantation. 1995 Jan 15;59(1):21-7.

PMID

7839424


Citation

Kamp MT, Fink NE, Enger C, Maguire MG, Stark WJ, Stulting RD. Patient-reported symptoms associated with graft reactions in high-risk patients in the collaborative corneal transplantation studies. Collaborative Corneal Transplantation Studies Research Group. Cornea. 1995 Jan;14(1):43-8.

PMID

7712736



Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Randomized

Primary Purpose

Treatment

Masking

Double


Study First Submitted

September 23, 1999

Study First Submitted Qc

September 23, 1999

Study First Posted

September 24, 1999

Last Update Submitted

September 16, 2009

Last Update Submitted Qc

September 16, 2009

Last Update Posted

September 17, 2009


ClinicalTrials.gov processed this data on August 24, 2018

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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