Modified Instrumentation for Surgery to Correct Trichiasis

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00886015
• Collaborator: Bill and Melinda Gates Foundation (Other)
• Enrollment: 1,927
• Location: 1
• Arms: 2
• Duration (Months): 37
• Patients Per Site Per Month: 52

Study Details

Study Description

Brief Summary

Trachoma, an ocular infection caused by C. trachomatis, is the second leading infectious cause of blindness worldwide. Years of repeated infection with C. trachomatis cause the eyelid to scar and contract and ultimately to rotate inward such that the eyelashes rub against the eyeball and abrade the cornea (trichiasis). The World Health Organization (WHO) has endorsed a multi-faceted strategy to combat trachoma which includes surgery to repair lids distorted by trachoma (trichiasis) in imminent danger of vision loss. Current evidence suggests that long-term success rates of trichiasis surgery are less than optimal due to variation in surgical technique. Previous research by this study team has demonstrated that shorter incisions have a higher rate of trichiasis recurrence. In addition, observations by this team's oculoplastic surgeon have led to the hypothesis that granuloma formation and lid contour abnormalities may result from current surgical practices. The objective of this study is to compare outcomes of trichiasis surgeries performed with the newly developed trachomatous trichiasis (TT) clamp versus surgeries following standard technique (bilamellar tarsal rotation procedure or BLTR).

Condition or Disease	Intervention/Treatment	Phase
Trachoma	Device: TT Clamp; Procedure: Standard BLTR Technique	N/A

Detailed Description

Field observations in 2005 by this study's PI and oculoplastic surgeon revealed some significant departures from current trichiasis surgery procedure (bilamellar tarsal rotation procedure or BTRP), as described in the WHO manual, "Trichiasis Surgery for Trachoma-the Bilamellar Tarsal Rotation Procedure". These procedural departures were felt to contribute to adverse outcomes, including trichiasis recurrence, granuloma formation and lid contour abnormalities. This study team developed a new surgical tool, the TT clamp, to help improve surgical outcomes following BLTR.

A randomized, single-masked clinical trial will be implemented in the Mtwara region in Tanzania. Study participants will be randomized on a 1:1 basis to surgery with the TT clamp or to surgery with standard BLTR equipment. All surgeries will take place at surgical centers in Mtwara and Lindi over an 8-month period.

Baseline assessment for severity of trichiasis and other predictors of surgical failure will be carried out prior to surgery. Follow-up is planned at 2 weeks (for suture removal), 6 weeks, 12 months, and 24 months post-surgery. At each follow-up visit participants will be assessed for evidence of unfavorable outcomes, including trichiasis recurrence, granuloma formation, and lid contour abnormalities. All outcomes will be assessed clinically by a trained observer who is masked to intervention status.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1927 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Partnership for the Rapid Elimination of Trachoma (PRET) Clinical Trial of Evaluation of Modified Instrumentation for Surgery to Correct Trichiasis
• Study Start Date: May 1, 2009
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TT Clamp The TT clamp will be used in trichiasis surgery.	Device: TT Clamp; trichiasis surgery performed with TT clamp
Active Comparator: Standard BLTR Technique Standard BLTR technique will be used in trichiasis surgery.	Procedure: Standard BLTR Technique; bilamellar tarsal rotation procedure in trichiasis surgery

Outcome Measures

Primary Outcome Measures

1. Number of Eyelids With Presence of Recurrent Trichiasis [2 years]

   Trichiasis: 1 or more eyelashes touching globe in primary position

2. Number of Eyelids With Pyogenic Granuloma [2 years]

   A pyogenic granuloma was defined as a sessile growth of 2 mm or more in diameter on the tarsal conjunctiva.

3. Number of Eyelids Experiencing an Unfavorable Outcome [2 years]

   At least 1 unfavorable outcome, including mild, moderate, or severe trichiasis; granuloma; or mild, moderate, or severe eyelid contour abnormality

4. Number of Eyelids With Normal or Mild Eyelid Contour Abnormalities vs Moderate or Severe Eyelid Contour Abnormalities [2 years]

   Eyelid contour abnormalities (ECA) were graded by photographs of the eyes. In the primary outcome measure, normal eyes and mild eyelid contour abnormalities are considered together, and moderate or severe eyelid contour abnormalities are considered together. ECA severity is defined as follows: Mild: Vertical deviation from the natural contour < 1 mm in height (less than half the pupil height in daylight) and affecting < 1/3 of horizontal eyelid length; Moderate: Vertical deviation from the natural contour 1-2 mm in height (about the pupil height in daylight) or affecting 1/3-2/3 of horizontal eyelid length; Severe: Vertical deviation from the natural contour > 2 mm in height (more than the pupil height in daylight) or a defect > 2/3 of the horizontal eyelid length

Secondary Outcome Measures

1. Number of Eyelids With Mild, Moderate, Severe, or no Eyelid Contour Abnormality [2 years]

   Eyelid contour abnormalities (ECA) were graded by photographs of the eyes. ECA severity is defined as follows: Mild: Vertical deviation from the natural contour < 1 mm in height (less than half the pupil height in daylight) and affecting < 1/3 of horizontal eyelid length; Moderate: Vertical deviation from the natural contour 1-2 mm in height (about the pupil height in daylight) or affecting 1/3-2/3 of horizontal eyelid length; Severe: Vertical deviation from the natural contour > 2 mm in height (more than the pupil height in daylight) or a defect > 2/3 of the horizontal eyelid length

2. Number of Eyelids With Normal, Mild, Moderate, or Severe Trachomatous Trichiasis [2 Years]

   Trichiasis is generally defined as 1 or more eyelashes touching globe in primary position. Classifications of trichiasis severity are as follows: Mild: 1-4 Eyelashes touching globe, no epilation OR 1-10 Eyelashes epilated, no eyelashes touching globe; Moderate: 5-9 Eyelashes touching globe, no epilation OR 1-4 Eyelashes touching globe and 1-10 eyelashes epilated; Severe: 5-9 Eyelashes touching globe and 1-10 eyelashes epilated OR 10 Eyelashes touching globe, regardless of epilation status OR 11-20 Eyelashes epilated, regardless of eyelashes touching globe OR Entire eyelid epilated, regardless of eyelashes touching globe

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Presence of upper lid trichiasis: defined by at least one eyelash touching the globe of the eye or evidence of epilation

• No previous report of trichiasis surgery in at least one eye with trichiasis:

• eyes with prior surgery are already at high risk due to the prior surgery, and their inclusion may decrease our ability to clearly evaluate our primary outcome

• if unilateral surgery has been performed previously, only the eye without prior history of surgery will be in the study, even if both eyes require surgery

• Age 18 or older (in order to provide consent as an adult): the vast majority of trichiasis patients are aged 18 or older

• At time of enrollment, subjects must state their intention to remain in the area for two years to facilitate study follow-up

Exclusion Criteria:

• Absence of upper lid trichiasis

• Prior trichiasis surgery on both eyes

• Age 18 or younger

• Subjects who are transiently in the area

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins University	Baltimore	Maryland	United States	21205

Sponsors and Collaborators

• Johns Hopkins University
• Bill and Melinda Gates Foundation

Investigators

• Principal Investigator: Emily Gower, PhD, Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Emily Gower, Associate Professor of Ophthalmology, Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT00886015
• Other Study ID Numbers: NA_00019216
• First Posted: Apr 22, 2009
• Last Update Posted: May 19, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Emily Gower, Associate Professor of Ophthalmology, Johns Hopkins University: Trachoma; trichiasis; bilamellar tarsal rotation procedure
• Additional relevant MeSH terms: Trachoma; Trichiasis

Study Results

Participant Flow

Recruitment Details	Community-level eye screenings were conducted to identify all trichiasis cases in the community. Patients were scheduled for surgery. On the day of surgery they were invited to join the study if they were eligible.
Pre-assignment Detail	963 individuals assigned to Trachomatous Trichiasis (TT) clamp, 6 did not participate. 3 refused surgery, 2 ineligible because of lower eyelid trichiasis only, 1 participant did not present for surgery. 964 individuals assigned to Standard, 4 did not participate. 2 refused surgery, 2 ineligible because of lower eyelid trichiasis only.

Arm/Group Title	Standard Instrumentation	TT Clamp
Arm/Group Description	Eyelids operated with standard BLTR instrumentation	Eyelids operated with the TT clamp instead of standard BLTR instrumentation. The TT clamp replaces the 2 hemostats and lid plate
Period Title: Overall Study
STARTED	1674	1671
COMPLETED	1674	1669
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Standard Instrumentation	TT Clamp	Total
Arm/Group Description	Eyelids operated with standard BLTR instrumentation	Eyelids operated with the TT clamp instead of standard BLTR instrumentation. The TT clamp replaces the 2 hemostats and lid plate	Total of all reporting groups
Overall Participants	960	957	1917
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.6 (13.1)	54.9 (13.5)	55.2 (13.3)
Sex/Gender, Customized (participants) [Number]
Female	722 75.2%	705 73.7%	1427 74.4%
Male	238 24.8%	252 26.3%	490 25.6%
Region of Enrollment (participants) [Number]
Tanzania	960 100%	957 100%	1917 100%
Trichiasis (eyelids) [Number]
mild	347	303	650
moderate	453	423	876
severe	874	945	1819

Outcome Measures

1. Primary Outcome

Title	Number of Eyelids With Presence of Recurrent Trichiasis
Description	Trichiasis: 1 or more eyelashes touching globe in primary position
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Of the 1671 eyes initially assigned to TT Clamp, 1 participant (2 eyelids) was excluded from TT Clamp analysis because participant died before follow-up.

Arm/Group Title	TT Clamp	Standard BLTR Technique
Arm/Group Description	The TT clamp will be used in trichiasis surgery. TT Clamp: trichiasis surgery performed with TT clamp	Standard BLTR technique will be used in trichiasis surgery. Standard BLTR Technique: bilamellar tarsal rotation procedure in trichiasis surgery
Measure Participants	956	960
Measure eyelids	1669	1674
Normal	948	1062
TT Recurrence	721	612

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TT Clamp, Standard BLTR Technique
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.36
	Confidence Interval	(2-Sided) 95%; 0.96 to 1.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Number of Eyelids With Pyogenic Granuloma
Description	A pyogenic granuloma was defined as a sessile growth of 2 mm or more in diameter on the tarsal conjunctiva.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Of the original 1771 eyelids assigned to TT clamp, 1 participant (2 eyelids) was excluded from TT Clamp analysis because participant died before follow-up

Arm/Group Title	TT Clamp	Standard BLTR Technique
Arm/Group Description	The TT clamp will be used in trichiasis surgery. TT Clamp: trichiasis surgery performed with TT clamp	Standard BLTR technique will be used in trichiasis surgery. Standard BLTR Technique: bilamellar tarsal rotation procedure in trichiasis surgery
Measure Participants	956	960
Measure eyelids	1669	1674
Granuloma	281	375
Normal	1388	1299

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TT Clamp, Standard BLTR Technique
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95%; 0.46 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Number of Eyelids Experiencing an Unfavorable Outcome
Description	At least 1 unfavorable outcome, including mild, moderate, or severe trichiasis; granuloma; or mild, moderate, or severe eyelid contour abnormality
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Of the original 1771 eyelids assigned to TT clamp, 1 participant (2 eyelids) was excluded from TT Clamp analysis because participant died before follow-up

Arm/Group Title	TT Clamp	Standard BLTR Technique
Arm/Group Description	The TT clamp will be used in trichiasis surgery. TT Clamp: trichiasis surgery performed with TT clamp	Standard BLTR technique will be used in trichiasis surgery. Standard BLTR Technique: bilamellar tarsal rotation procedure in trichiasis surgery
Measure Participants	956	960
Measure eyelids	1669	1674
Any unfavorable outcome	1017	1055
Normal	652	619

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TT Clamp, Standard BLTR Technique
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.66 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Number of Eyelids With Normal or Mild Eyelid Contour Abnormalities vs Moderate or Severe Eyelid Contour Abnormalities
Description	Eyelid contour abnormalities (ECA) were graded by photographs of the eyes. In the primary outcome measure, normal eyes and mild eyelid contour abnormalities are considered together, and moderate or severe eyelid contour abnormalities are considered together. ECA severity is defined as follows: Mild: Vertical deviation from the natural contour < 1 mm in height (less than half the pupil height in daylight) and affecting < 1/3 of horizontal eyelid length; Moderate: Vertical deviation from the natural contour 1-2 mm in height (about the pupil height in daylight) or affecting 1/3-2/3 of horizontal eyelid length; Severe: Vertical deviation from the natural contour > 2 mm in height (more than the pupil height in daylight) or a defect > 2/3 of the horizontal eyelid length
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Of the original 1771 eyelids assigned to TT clamp, 1 participant (2 eyelids) was excluded from TT Clamp analysis because participant died before follow-up

Arm/Group Title	TT Clamp	Standard BLTR Technique
Arm/Group Description	The TT clamp will be used in trichiasis surgery. TT Clamp: trichiasis surgery performed with TT clamp	Standard BLTR technique will be used in trichiasis surgery. Standard BLTR Technique: bilamellar tarsal rotation procedure in trichiasis surgery
Measure Participants	956	960
Measure eyelids	1669	1674
No/Mild ECA	1549	1500
Moderate/Severe ECA	120	174

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TT Clamp, Standard BLTR Technique
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; 0.44 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Eyelids With Mild, Moderate, Severe, or no Eyelid Contour Abnormality
Description	Eyelid contour abnormalities (ECA) were graded by photographs of the eyes. ECA severity is defined as follows: Mild: Vertical deviation from the natural contour < 1 mm in height (less than half the pupil height in daylight) and affecting < 1/3 of horizontal eyelid length; Moderate: Vertical deviation from the natural contour 1-2 mm in height (about the pupil height in daylight) or affecting 1/3-2/3 of horizontal eyelid length; Severe: Vertical deviation from the natural contour > 2 mm in height (more than the pupil height in daylight) or a defect > 2/3 of the horizontal eyelid length
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Of the 1771 participants originally assigned to TT Clamp, 1 participant (2 eyelids) was excluded from TT Clamp analysis because participant died before follow-up

Arm/Group Title	TT Clamp	Standard BLTR Technique
Arm/Group Description	The TT clamp will be used in trichiasis surgery. TT Clamp: trichiasis surgery performed with TT clamp	Standard BLTR technique will be used in trichiasis surgery. Standard BLTR Technique: bilamellar tarsal rotation procedure in trichiasis surgery
Measure Participants	956	960
Measure eyelids	1669	1674
Normal	1397	1278
Mild ECA	152	222
Moderate ECA	89	131
Severe ECA	31	43

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TT Clamp, Standard BLTR Technique
	Comments	Mild ECA compared with Normal
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.64
	Confidence Interval	(2-Sided) 95%; 0.42 to 0.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TT Clamp, Standard BLTR Technique
	Comments	Moderate ECA compared with Normal
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.63
	Confidence Interval	(2-Sided) 95%; 0.39 to 1.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	TT Clamp, Standard BLTR Technique
	Comments	Severe ECA compared with Normal
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; 0.35 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Number of Eyelids With Normal, Mild, Moderate, or Severe Trachomatous Trichiasis
Description	Trichiasis is generally defined as 1 or more eyelashes touching globe in primary position. Classifications of trichiasis severity are as follows: Mild: 1-4 Eyelashes touching globe, no epilation OR 1-10 Eyelashes epilated, no eyelashes touching globe; Moderate: 5-9 Eyelashes touching globe, no epilation OR 1-4 Eyelashes touching globe and 1-10 eyelashes epilated; Severe: 5-9 Eyelashes touching globe and 1-10 eyelashes epilated OR 10 Eyelashes touching globe, regardless of epilation status OR 11-20 Eyelashes epilated, regardless of eyelashes touching globe OR Entire eyelid epilated, regardless of eyelashes touching globe
Time Frame	2 Years

Outcome Measure Data

Analysis Population Description

Of the 1669 TT eyelids and 1674 BLTR eyelids included in the initial analysis, 13 eyes (4 in the TT clamp group, 9 in the BLTR group) without TT at 1 year underwent operation between years 1 and 2. They are not included in the data for severity of recurrence because we do not know the TT severity.

Arm/Group Title	TT Clamp	Standard BLTR Technique
Arm/Group Description	The TT clamp will be used in trichiasis surgery. TT Clamp: trichiasis surgery performed with TT clamp	Standard BLTR technique will be used in trichiasis surgery. Standard BLTR Technique: bilamellar tarsal rotation procedure in trichiasis surgery
Measure Participants	954	956
Measure eyelids	1665	1665
Normal	948	1062
Mild TT Recurrence	476	417
Moderate TT Recurrence	121	86
Severe TT Recurrence	120	100

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TT Clamp, Standard BLTR Technique
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 95%; 0.97 to 1.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	through 2 years
Arm/Group Title	Standard Instrumentation		TT Clamp
Arm/Group Description	Eyelids operated with standard BLTR instrumentation		Eyelids operated with the TT clamp instead of standard BLTR instrumentation. The TT clamp replaces the 2 hemostats and lid plate
All Cause Mortality
	Standard Instrumentation		TT Clamp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Standard Instrumentation		TT Clamp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/960 (0%)		0/957 (0%)
Other (Not Including Serious) Adverse Events
	Standard Instrumentation		TT Clamp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/960 (1.6%)		12/957 (1.3%)
Eye disorders
Excess intraoperative bleeding	4/960 (0.4%)	4	0/957 (0%)	0
Division of Eyelid Margin	2/960 (0.2%)	2	0/957 (0%)	0
postoperative bleeding	5/960 (0.5%)	5	4/957 (0.4%)	4
necrosis	4/960 (0.4%)	4	8/957 (0.8%)	8

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.