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Cornea Preservation Time Study (CPTS)

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ClinicalTrials.gov Identifier: NCT01537393
Recruitment Status : Completed
First Posted : February 23, 2012
Results First Posted : April 23, 2018
Last Update Posted : April 23, 2018
Sponsor:
Collaborators:
National Eye Institute (NEI)
Jaeb Center for Health Research
Information provided by (Responsible Party):
Jonathan Lass, MD, Case Western Reserve University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Cornea Preservation Time
Endothelial Keratoplasty
Transplant Success
Endothelial Cell Density
Intervention Biological: Cornea tissue transplant
Enrollment 1174
Recruitment Details  
Pre-assignment Details Randomization was at eye level. When both eyes of a participant were included, the eye undergoing surgery 1st was assigned randomly to a PT group and the 2nd eye to the other group. 2 eyes had their assigned donor corneas inadvertently switched, and resulted in 1 of these participants receiving both study eyes from 8-14d group.
Arm/Group Title 0-7d Preservation Time (PT) Group 8-14d Preservation Time (PT) Group
Hide Arm/Group Description

Subjects in this arm will receive cornea tissue preserved for up to 7 days prior to transplant.

Cornea tissue transplant: Cornea tissue preserved either 7 or less days or 8 to 14 days.

Subjects in this arm will receive cornea tissue preserved for 8 to 14 days prior to transplant.

Cornea tissue transplant: Cornea tissue preserved either 7 or less days or 8 to 14 days.

Period Title: Overall Study
Number of participants Number of units (eyes) Number of participants Number of units (eyes)
Started [1] 707 707 698 699
Completed [2] 553 553 507 508
Not Completed 154 154 191 191
Reason Not Completed
Exclude prior to study             32                         44            
Death             20                         32            
Withdrawal by Subject             18                         17            
Lost to Follow-up             53                         48            
Failure - Regrafted             28                         43            
Failure - Not regrafted             2                         6            
Censored (severe event unrelated to PT)             1                         1            
[1]
1046 eyes from 1151 participants randomized
[2]
Study eyes with 3-year visit completed
Arm/Group Title Preservation Time Group 1 Preservation Time Group 2 Total
Hide Arm/Group Description

Subjects in this arm will receive cornea tissue preserved for up to 7 days prior to transplant.

Cornea tissue transplant: Cornea tissue preserved either 7 or less days or 8 to 14 days.

Subjects in this arm will receive cornea tissue preserved for 8 to 14 days prior to transplant.

Cornea tissue transplant: Cornea tissue preserved either 7 or less days or 8 to 14 days.

Total of all reporting groups
Overall Number of Baseline Participants 675 654 1090
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
675 655 1330
Hide Baseline Analysis Population Description
Analyses conducted at eye level. 1330 study eyes of 1090 participants underwent descemet stripping automated endothelial keratoplasty. 480 eyes completed bilateral surgery (240 participants), 1 participant had both eyes received cornea in 8-14 days group. 435 and 414 participants underwent unilateral surgery in 0-7 and 8-14 days groups.
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 675 eyes 655 eyes 1330 eyes
70
(64 to 76)
70
(64 to 77)
70
(64 to 76)
Sex: Female, Male  
Count of Units
Unit of measure:  Eyes
Number Analyzed 675 eyes 655 eyes 1330 eyes
Female
409
  60.6%
392
  59.8%
801
  60.2%
Male
266
  39.4%
263
  40.2%
529
  39.8%
Race/Ethnicity, Customized  
Count of Units
Unit of measure:  Eyes
Number Analyzed 675 eyes 655 eyes 1330 eyes
White
613
  90.8%
594
  90.7%
1207
  90.8%
African American
26
   3.9%
21
   3.2%
47
   3.5%
Hispanic or Latino
19
   2.8%
25
   3.8%
44
   3.3%
Asian
7
   1.0%
5
   0.8%
12
   0.9%
American India or Alaskan Native
1
   0.1%
2
   0.3%
3
   0.2%
More than 1 race
6
   0.9%
3
   0.5%
9
   0.7%
Unknown or not reported
3
   0.4%
5
   0.8%
8
   0.6%
History of Diabetes  
Count of Units
Unit of measure:  Eyes
Number Analyzed 675 eyes 655 eyes 1330 eyes
116
  17.2%
126
  19.2%
242
  18.2%
Current cigarette smoker  
Count of Units
Unit of measure:  Eyes
Number Analyzed 675 eyes 655 eyes 1330 eyes
45
   6.7%
45
   6.9%
90
   6.8%
Received any immunizations or vaccinations in last 3 mo  
Count of Units
Unit of measure:  Eyes
Number Analyzed 675 eyes 655 eyes 1330 eyes
92
  13.6%
81
  12.4%
173
  13.0%
Prior glaucoma surgery  
Count of Units
Unit of measure:  Eyes
Number Analyzed 675 eyes 655 eyes 1330 eyes
18
   2.7%
13
   2.0%
31
   2.3%
Glaucoma medication currently being used  
Count of Units
Unit of measure:  Eyes
Number Analyzed 675 eyes 655 eyes 1330 eyes
45
   6.7%
54
   8.2%
99
   7.4%
Diagnosis  
Count of Units
Unit of measure:  Eyes
Number Analyzed 675 eyes 655 eyes 1330 eyes
Pseudophakic corneal edema without FECD
44
   6.5%
29
   4.4%
73
   5.5%
Aphakic corneal edema without FECD
0
   0.0%
2
   0.3%
2
   0.2%
Fuchs endothelial corneal dystrophy (FECD)
631
  93.5%
624
  95.3%
1255
  94.4%
Corneal Dystrophy other than FECD (Fuchs endothelial corneal dystrophy))   [1] 
Count of Units
Unit of measure:  Eyes
Number Analyzed 675 eyes 655 eyes 1330 eyes
No
630
  93.3%
623
  95.1%
1253
  94.2%
Keratoconus
1
   0.1%
0
   0.0%
1
   0.1%
EBMD (epithelial basement membrane dystrophy)
38
   5.6%
29
   4.4%
67
   5.0%
Other
6
   0.9%
3
   0.5%
9
   0.7%
[1]
Measure Description: During the slit lamp exam performed using the investigator's usual routine, the presence of other corneal dystrophies was recorded; EBMD=epithelial basement membrane dystrophy
Stromal corneal vessels present (but not visually significant)  
Count of Units
Unit of measure:  Eyes
Number Analyzed 675 eyes 655 eyes 1330 eyes
4
   0.6%
1
   0.2%
5
   0.4%
Central subepithelial/stromal scarring present (not affect postoperative stromal clarity assessment)  
Count of Units
Unit of measure:  Eyes
Number Analyzed 675 eyes 655 eyes 1330 eyes
37
   5.5%
48
   7.3%
85
   6.4%
Peripheral anterior synechiae present (nongonioscopic)  
Count of Units
Unit of measure:  Eyes
Number Analyzed 675 eyes 655 eyes 1330 eyes
4
   0.6%
2
   0.3%
6
   0.5%
Preoperative lens status   [1] 
Count of Units
Unit of measure:  Eyes
Number Analyzed 675 eyes 655 eyes 1330 eyes
Phakic
341
  50.5%
351
  53.6%
692
  52.0%
Aphakic
0
   0.0%
2
   0.3%
2
   0.2%
Pseudophakic posterior chamber intraocular lens
334
  49.5%
302
  46.1%
636
  47.8%
[1]
Measure Description: During the slit lamp exam performed using the investigator's usual routine, the state of the crystalline lens was described as phakic (present), aphakic (removed), or pseudophakic (removed with posterior chamber intraocular lens inserted)
Postoperative lens status  
Count of Units
Unit of measure:  Eyes
Number Analyzed 675 eyes 655 eyes 1330 eyes
Phakic
4
   0.6%
6
   0.9%
10
   0.8%
Pseudophakic posterior chamber intraocular lens
671
  99.4%
649
  99.1%
1320
  99.2%
Intraocular pressure (IOP)  
Median (Inter-Quartile Range)
Unit of measure:  Mm Hg
Number Analyzed 675 eyes 655 eyes 1330 eyes
15
(12 to 17)
15
(12 to 17)
15
(12 to 17)
1.Primary Outcome
Title Number of Eyes With Corneal Graft Failure Within 3 Years of Surgery
Hide Description

Graft failure, defined as the occurrence of one of the following within 3 years of surgery:

  • Regrafting of the study eye for any reason
  • Cornea which remains cloudy without clearing, according to the following:

    1. cloudy cornea on the first postoperative day which does not clear within 8 weeks OR
    2. cloudy cornea which was initially clear postoperatively but becomes and remains cloudy for 3 months without clearing.
Time Frame Study eye will be assessed for this outcome for 3 years following surgery
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analyzed number of eyes in each group (Overall 1090 unique participants)
Arm/Group Title Preservation Time Group 1 Preservation Time Group 2
Hide Arm/Group Description:

Subjects in this arm will receive cornea tissue preserved for up to 7 days prior to transplant.

Cornea tissue transplant: Cornea tissue preserved either 7 or less days or 8 to 14 days.

Subjects in this arm will receive cornea tissue preserved for 8 to 14 days prior to transplant.

Cornea tissue transplant: Cornea tissue preserved either 7 or less days or 8 to 14 days.

Overall Number of Participants Analyzed 675 654
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
675 655
Count of Units
Unit of Measure: Eyes
30
   4.4%
49
   7.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Preservation Time Group 1, Preservation Time Group 2
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments The two treatment groups will be declared equivalent if the one-sided 95% confidence interval for the difference in proportions excludes the pre-defined non-inferiority limit of 4%.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 3.2
Confidence Interval (1-Sided) 95%
5.4
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Preservation Time Group 1, Preservation Time Group 2
Comments [Not Specified]
Type of Statistical Test Other
Comments Confounding and treatment interactions were assessed in Cox proportional hazards regression models
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Regression, Cox
Comments Unadjusted Hazard Ratio
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.71
Confidence Interval (2-Sided) 95%
1.09 to 2.71
Estimation Comments [Not Specified]
2.Primary Outcome
Title Endothelial Cell Density (ECD)
Hide Description Endothelial cell density at 3 years from surgery, conditional on graft survival at 3 years from surgery.
Time Frame 3 years from surgery
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Eyes with graft success and a gradable image at 3 year (945 eyes of 769 unique participants)
Arm/Group Title Preservation Time Group 1 Preservation Time Group 2
Hide Arm/Group Description:

Subjects in this arm will receive cornea tissue preserved for up to 7 days prior to transplant.

Cornea tissue transplant: Cornea tissue preserved either 7 or less days or 8 to 14 days.

Subjects in this arm will receive cornea tissue preserved for 8 to 14 days prior to transplant.

Cornea tissue transplant: Cornea tissue preserved either 7 or less days or 8 to 14 days.

Overall Number of Participants Analyzed 485 459
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
485 460
Mean (Standard Deviation)
Unit of Measure: Cells per square millimeter
1722  (626) 1642  (631)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Preservation Time Group 1, Preservation Time Group 2
Comments [Not Specified]
Type of Statistical Test Other
Comments The primary analysis to assess the effect of PT on 3 year ECD was conducted with a mixed linear model adjusting for baseline ECD, corneal diagnosis, and potential confounders, including storage solution, preparation by eye bank vs surgeon, and accounting for correlated data from participants with 2 study eyes or 2 corneas from the same donor.
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method Mixed Models Analysis
Comments Adjusted for baseline ECD, diagnosis, storage solution, preparation by eye bank/surgeon, participants with 2 study eyes/ 2 corneas from the same donor
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 73
Confidence Interval (2-Sided) 95%
8 to 138
Estimation Comments [Not Specified]
Time Frame Through study completion, up to 5 years
Adverse Event Reporting Description Adverse event was collected at eye level
 
Arm/Group Title 0-7d Preservation Time Group 8-14d Preservation Time Group
Hide Arm/Group Description

Subjects in this arm will receive cornea tissue preserved for up to 7 days prior to transplant.

Cornea tissue transplant: Cornea tissue preserved either 7 or less days or 8 to 14 days.

Subjects in this arm will receive cornea tissue preserved for 8 to 14 days prior to transplant.

Cornea tissue transplant: Cornea tissue preserved either 7 or less days or 8 to 14 days.

All-Cause Mortality
0-7d Preservation Time Group 8-14d Preservation Time Group
Affected / at Risk (%) Affected / at Risk (%)
Total   20/675 (2.96%)   32/654 (4.89%) 
Show Serious Adverse Events Hide Serious Adverse Events
0-7d Preservation Time Group 8-14d Preservation Time Group
Affected / at Risk (%) Affected / at Risk (%)
Total   1/675 (0.15%)   2/654 (0.31%) 
Eye disorders     
Endophthalmitis  [1]  1/675 (0.15%)  0/654 (0.00%) 
Microbial keratitis  [2]  0/675 (0.00%)  2/654 (0.31%) 
Indicates events were collected by systematic assessment
[1]
One case of bacterial endophthalmitis occurred in the 0-7d PT group 4 days after surgery
[2]
Microbial keratitis (bacterial, fungal, parasitic) within 3 months of endothelial keratoplasty (EK) 2 cases of fungal keratitis occurred in the 8-14d PT group 13 and 43 days after surgery
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
0-7d Preservation Time Group 8-14d Preservation Time Group
Affected / at Risk (%) Affected / at Risk (%)
Total   0/675 (0.00%)   0/654 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Jonathan Lass
Organization: CaseWestern
Phone: 2168448368
Responsible Party: Jonathan Lass, MD, Case Western Reserve University
ClinicalTrials.gov Identifier: NCT01537393     History of Changes
Other Study ID Numbers: CPTS
1U10EY020798-01A1 ( U.S. NIH Grant/Contract )
1U10EY020797-01A1 ( U.S. NIH Grant/Contract )
First Submitted: February 15, 2012
First Posted: February 23, 2012
Results First Submitted: March 14, 2018
Results First Posted: April 23, 2018
Last Update Posted: April 23, 2018