Evaluating the Role of Incision Height in Trichiasis Surgery Outcomes
Phase: NA
Conditions: Trichiasis, Surgery
Sponsor: University of North Carolina, Chapel Hill

 
 
Maximizing Trichiasis Surgery Success  
Trial Protocol 
 
 
 
NCT number NCT03100747 
Document Date 10/10/2021 
 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
  
 
 
Maximizing Trichiasis Surgery Success  
Trial Protocol 
 
Version Number:  2.4 
10 October 2021 
 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
i 
 
 
STATEMENT OF COMPLIANCE 
The study will be conducted in accordance with the International Conference on 
Harmonisation guidelines for Good Clinical Practice (ICH E6), the Code of Federal 
Regulations on the Protection of Human Subjects (45 CFR Part 46), and the NIDCR 
Clinical Terms of Award. All personnel involved in the conduct of this study have 
completed human subjects protection training. 
 
This protocol is modeled in part based on NIDCR Clinical Trial (Interventional) Protocol 
Template v4.0 - 20140103

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
ii 
 
SIGNATURE PAGE 
The signature below constitutes the approval of this protocol and the attachments, and 
provides the necessary assurances that this trial will be conducted according to all 
stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable US federal 
regulations and ICH guidelines. 
Principal Investigator or Clinical Site Investigator: 
Signed: 
 
Date: 10 October 2021 
 
Name: Emily W. Gower, PhD 
 
Title: Associate Professor 
 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
iii 
 
TABLE OF CONTENTS 
PAGE 
STATEMENT OF COMPLIANCE .................................................................................................. I 
THIS PROTOCOL IS MODELED IN PART BASED ON NIDCR CLINICAL TRIAL 
(INTERVENTIONAL) PROTOCOL TEMPLATE V4.0 - 20140103 ........................................ I 
SIGNATURE PAGE ...................................................................................................................... II 
TABLE OF CONTENTS ............................................................................................................... III 
PROTOCOL SUMMARY .............................................................................................................. V 
STUDY DESIGN SCHEMATIC: .................................................................................................. VII 
1 
KEY ROLES AND CONTACT INFORMATION ....................................................................... 8 
2 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ............ 9 
2.1 
Background and Rationale .......................................................................................... 9 
2.2 
Potential Risks and Benefits ..................................................................................... 10 
3 
OBJECTIVES ........................................................................................................................ 12 
3.1 
Study Objectives ....................................................................................................... 12 
3.2 
Study Outcome Measures ......................................................................................... 12 
4 
STUDY ENROLLMENT AND WITHDRAWAL ...................................................................... 14 
4.1 
Subject Inclusion Criteria .......................................................................................... 14 
4.2 
Subject Exclusion Criteria ......................................................................................... 14 
4.3 
Strategies for Recruitment and Retention ................................................................. 14 
4.4 
Treatment Assignment Procedures ........................................................................... 15 
4.4.1 
Randomization Procedures ........................................................................ 15 
4.4.2 
Masking Procedures ................................................................................... 15 
4.5 
Subject Withdrawal ................................................................................................... 15 
5 
STUDY INTERVENTION ...................................................................................................... 16 
5.1 
Study Procedural Intervention Description ................................................................ 16 
5.2 
Procedures for Training of Clinicians on Procedural Intervention ............................. 16 
5.3 
Assessment of Clinician and/or Subject Compliance with Study Procedural 
Intervention ............................................................................................................. 17 
6 
STUDY SCHEDULE ............................................................................................................. 18 
6.1 
Eligibility Screening and Enrollment (Day 0) ............................................................. 18 
6.2 
Baseline Ocular Exam and Surgery (Day 0) ............................................................. 19 
6.3 
Follow up Visits ......................................................................................................... 19 
6.4 
Unscheduled Visit ..................................................................................................... 19 
6.5 
Timeline and Feasibility of Adhering to Study Schedule ........................................... 21 
7 
STUDY PROCEDURES /EVALUATIONS ............................................................................ 23 
8 
PROVISIONS FOR MONITORING STUDY PROGRESS .................................................... 24 
9 
STATISTICAL CONSIDERATIONS ...................................................................................... 25 
9.1 
Study Hypotheses ..................................................................................................... 25 
9.2 
Sample Size Considerations ..................................................................................... 26 
9.3 
Analysis Plan ............................................................................................................. 27 
10 
QUALITY CONTROL AND QUALITY ASSURANCE .......................................................... 31 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
iv 
 
10.1 
Training ................................................................................................................... 31 
10.2 
Quality Monitoring ................................................................................................... 31 
10.3 
Data and Safety Monitoring Board .......................................................................... 32 
11 
ETHICS/PROTECTION OF HUMAN SUBJECTS .............................................................. 33 
11.1 
Ethical Standards .................................................................................................... 33 
11.2 
Institutional Review Board ....................................................................................... 33 
11.3 
Informed Consent Process ...................................................................................... 33 
11.4 
Exclusion of Women, Minorities, and Children (Special Populations) ..................... 33 
11.5 
Subject Confidentiality ............................................................................................. 34 
12 
COMMUNITY INVOLVEMENT PLAN ................................................................................. 35 
13 
PUBLICATION/DATA SHARING POLICY .......................................................................... 36 
 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
v 
 
 PROTOCOL SUMMARY 
Title: 
Evaluating the Role of Incision Height in Trichiasis Surgery 
Outcomes 
Précis: 
In this trial we will randomize 4,953 individuals with previously 
unoperated trichiasis on a 1:1:1 basis to bilamellar tarsal 
rotation trichiasis surgery with an incision height of 3mm, 
bilamellar tarsal rotation trichiasis surgery with an incision 
height of 5 mm, or Trabut surgery.  Participants will receive 
trichiasis surgery and will be followed at 1 day, 2 weeks, 6 
weeks,12 months and 3 years after surgery.  The primary 
outcome is development of post-operative trachomatous 
trichiasis (PTT) within 12-18 months after surgery.  Logistic 
regression analyses will be performed to compare the rates of 
PTT in the 3 versus 5 mm incision BLTR groups, in the 3 mm 
BLTR versus Trabut group, and in the 5 mm BLTR versus 
Trabut group, adjusting for demographic characteristics and 
pre-operative trichiasis severity.     
Objectives: 
 
Primary objectives:  
1) Examine whether the rate of post-operative trichiasis 
differs significantly for incisions placed 3 mm from the 
eyelid margin compared to incisions place 5 mm from 
the eyelid margin.   
2) Examine whether the rate of post-operative trichiasis 
differs significantly between surgery performed with the 
Trabut procedure versus bilamellar tarsal rotation with 3 
mm incision height. 
3) Examine whether the rate of post-operative trichiasis 
differs significantly between surgery performed with the 
Trabut procedure versus bilamellar tarsal rotation with 5 
mm incision height. 
Secondary objectives:  
1) Determine whether the frequency of moderate/severe 
eyelid contour abnormalities differs following surgery 
performed with the bilamellar procedure when the target 
incision height is 3 mm versus 5 mm   
2) Compare the frequency of moderate/severe eyelid 
contour abnormalities at one year between surgeries 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
vi 
 
performed with bilamellar 5 mm incision height and 
Trabut.  
3) Compare the frequency of moderate/severe eyelid 
contour abnormalities at one year between surgeries 
performed with bilamellar 5 mm incision height and 
Trabut.  
 
Population: 
Participants will be recruited from the Hadiya Zone of the 
SNNPR Region in Ethiopia.  All individuals with previously 
unoperated trichiasis in at least one eye, aged >18 years, and 
living in the area will be eligible to participate. We aim to enroll 
1,500 individuals during the 2016/2017 surgical campaigns 
being supervised by Orbis International (we will recruit from 
January to April), an additional 2,500 individuals during the 
2017/2018 campaign (October to April), and approximately 
1,000 in the Fall/Winter 2018/2019 campaign. 
Description of 
Intervention: 
Trabut surgery involves a partial-thickness incision through the 
upper eyelid parallel to the eyelid margin.  Bilamellar tarsal 
rotation involves a full-thickness incision through the upper 
eyelid.  For bilamellar surgery, the height of the incision will be 
assigned at 3 mm or 5 mm from the eyelid margin. For Trabut, 
it will be assigned at 3 mm.  
Study Duration: 
6 years 
Subject 
Participation 
Duration: 
3 years 
Estimated Time to 
Complete 
Enrollment: 
Recruitment is scheduled for mid-January 2017 - April 2017 
and mid-October 2017 through March 2018 to account for the 
rainy season. 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
vii 
 
 STUDY DESIGN SCHEMATIC: 
 
Prior to  
Enrollment 
 
 
 
 
 
 
 
 
 
 
Visit 1 
Baseline and  
Surgery 
 
 
 
Visit 2 
Suture Removal 
 
 
Visit 3 
6-week Exam 
 
 
 
Visit 4 
12-month Exam 
 
 
 
Visit 5 
3 year- Exam 
Screen potential subjects by inclusion and exclusion criteria;  
Obtain informed consent. Total N to enroll: 4953 
Perform ocular exam to characterize presence of trichiasis for each eyelid 
(Baseline Ocular Exam form); perform trichiasis surgery for all affected eyelids 
and record surgical details on Surgical Evaluation Form. 
  (Study intervention to be administered during surgery). 
Ocular exam to evaluate presence of trichiasis, eyelid contour abnormalities and 
granuloma formation. Record results on 6-week Ocular Exam form.  
Randomize 
Arm 2: Bilamellar 5mm  
N = 1651 
Arm 1: Bilamellar 3mm  
N = 1651 
Remove sutures and complete 2-week visit form to assess eyelid characteristics. 
Assessment of participants. Ocular exam to evaluate presence of trichiasis, eyelid 
contour abnormalities and granuloma formation. Record results on 12-month 
Ocular Exam form.  
Arm 3: Trabut 3mm 
N = 1651 
Final assessment of participants. Ocular exam to evaluate presence of trichiasis, 
eyelid contour abnormalities and granuloma formation. Record results on 3-year 
Ocular Exam form.  

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
8 
 
1 KEY ROLES AND CONTACT INFORMATION 
 
Principal 
Investigator:   
Emily W. Gower, PhD 
Gillings School of Global Public Health 
University of North Carolina at Chapel Hill 
Chapel Hill, North Carolina 
egower@email.unc.edu  
 
 
 
 
Clinical Site 
Investigators: 
Alemayehu Sisay, MD; Orbis International 
Institutions: 
 
Orbis International 
Rebecca House 
Addis Ababa, Ethiopia 
 
Johns Hopkins School of Medicine 
600 North Wolfe Street 
Baltimore, MD 21287 
   
Other Key 
Personnel: 
Amir Bedri, MD (trainer and external evaluator) 
Belay Bayissasse, MPH (project director) 
Shannath L. Merbs, MD PhD (JHU SoM site PI) 
Beatriz Munoz, MS (senior statistician) 
 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
9 
 
2 INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE  
2.1 
Background and Rationale 
Trichiasis is an important cause of blindness in developing countries with limited access 
to water and sanitation measures.  The disease primarily affects adult women, although 
in areas where trachoma is highly-endemic, trichiasis is occasionally diagnosed in 
young children.  Surgery is available to correct trichiasis, but long-term success rates 
are suboptimal in many settings.  Two primary surgical procedures are used, bilamellar 
tarsal rotation (BLTR; bilamellar) and posterior lamellar tarsal rotation (PLTR), also 
known as Trabut.   
 
Surgical Procedure Comparison 
A recent trial conducted in the Amhara region of Ethiopia compared BLTR and Trabut 
and found a significant reduction in post-operative trichiasis following Trabut as 
compared to BLTR (22% vs. 13%; Adjusted Odds Ratio 1.96; 95% CI: 1.40-2.75).   The 
trial employed Trabut-trained surgeons who received conversion training to perform 
BLTR. Each surgeon performed both procedures as part of the trial. The trial was 
exceptionally well run, and some programs are now strictly training surgeons with 
Trabut.  However, there is much debate over whether the trial results are broadly 
applicable for experienced surgeons who were first trained in BLTR and for newly 
trained surgeons.  Specifically, since the release of the trial results, two meetings of the 
global trichiasis community have been held (one a WHO-sponsored meeting of 
trichiasis experts and the other the annual program review of the organization 
performing the largest volume of trichiasis surgeries worldwide, which included global 
experts from most trachoma-endemic countries). At both meetings, experts strongly 
recommended that another trial should be conducted which utilizes BLTR surgeons who 
receive conversion training to Trabut. Additionally, Dr. Wondu Alemayehu is a member 
of the planned trials and has indicated strong in-country support for the need for an 
additional study to examine this question.  In the planned trial, we will compare post-
operative trichiasis rates for surgeries performed with each of these procedures.  
Surgeons will be either newly trained in both procedures or will be BLTR surgeons who 
have received conversion training in Trabut and have performed at least 100 Trabut 
surgeries.  
Incision Height Comparison 
In both the BLTR and Trabut procedures an incision is made in the eyelid, parallel to the 
eyelid margin, such that inturned eyelashes can be corrected to their normal position. 
Currently, the recommended height for making the incision is 3 mm above the eyelid 
margin.  However, preliminary evidence from bilamellar surgery trials suggests that this 
height may not be the best height for achieving optimal outcomes.  Data from both the 
PRET trial and the recent Trabut versus BLTR trial show reduced post-operative 
trichiasis among eyelids operated with the BLTR procedure with an incision scar height 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
10 
 
of 5 mm at 1 year versus a lower incision scar height. Specifically, the PRET trial 
examined the role of a surgical clamp (the TT Clamp) in improving bilamellar trichiasis 
surgery outcomes. Use of the TT clamp improved eyelid contour abnormalities and 
granuloma formation, but it did not improve risk of trichiasis returning (post-operative 
trichiasis).  Evaluation of incision height scars for a subset of this population suggests 
that incisions that are made closer to the eyelid margin are more likely to develop post-
operative trichiasis than eyelids with an incision further away from the eyelid margin.  
When surgeons perform TT surgery with the clamp, they are guided on where to place 
the incision, and by design of the clamp, the height of the incision is limited; hence, it is 
possible that the TT clamp did not improve post-operative trichiasis rates because the 
incisions in the TT clamp arm were closer to the eyelid margin than eyelids operated 
with standard instrumentation (without a TT clamp).  We have conducted a similar 
analysis of incision scar heights for the Amhara based BLTR vs. Trabut trial and found 
similar results for the BLTR surgeries in that study.  Incision scar height and post-
operative trichiasis were not correlated in Trabut surgeries; however, rates of post-
operative trichiasis in the higher scar height BLTR surgeries were similar to rates in the 
Trabut arm.  
One goal of the planned trial is to determine whether altering the incision height to 5 mm 
can improve surgical outcomes. We will compare target incision heights of 3 mm and 5 
mm among BLTR surgeries.   We selected this comparison since 2 studies have 
provided a suggestion that increasing the incision height in BLTR surgeries could 
positively affect post-operative trichiasis rates.  
The follow up period for this trial is one year after surgery.  Historical evidence suggests 
that the majority of post-operative trichiasis occurs within the first year after surgery, and 
that most recurrence that happens after one year is more related to disease severity 
than to the manner in which the procedure was performed.   
2.2 
Potential Risks and Benefits 
Potential Risks 
The risks associated with this study are minimal.  Trichiasis surgery is a standard 
procedure commonly performed in many countries, and all subjects enrolled in this 
study would receive trichiasis surgery regardless of whether they participate in the 
clinical trial.  Theoretically, increasing the incision height could result in an increased 
risk of eyelid contour abnormalities since a larger portion of the tarsus must be everted.  
Preliminary data suggest that higher incision heights are not associated with an 
increased risk of eyelid contour abnormalities.  However, it is important to be aware of 
this possible risk.  
Potential Benefits 
Participants enrolled in this study will not benefit directly from this study.  Most trichiasis 
surgery programs do not follow their patients after sutures are removed.  In this study, 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
11 
 
we will evaluate patients 6 weeks,12 months and 3 years after surgery.  Participants 
may view this as a benefit.  

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
12 
 
3 OBJECTIVES 
3.1 
Study Objectives 
This study has three primary objectives: 
1) Examine whether the rate of post-operative trichiasis differs significantly for 
incisions placed 3 mm from the eyelid margin compared to incisions place 5 mm 
from the eyelid margin.   
2) Examine whether the rate of post-operative trichiasis differs significantly between 
surgery performed with the Trabut procedure versus bilamellar tarsal rotation 
with 3 mm incision height. 
3) Examine whether the rate of post-operative trichiasis differs significantly between 
surgery performed with the Trabut procedure versus bilamellar tarsal rotation 
with 5 mm incision height. 
Secondary objectives:  
1) Determine whether the frequency of moderate/severe eyelid contour 
abnormalities differs following surgery performed with the bilamellar procedure 
when the target incision height is 3 mm versus 5 mm   
2) Compare the frequency of moderate/severe eyelid contour abnormalities at one 
year between surgeries performed with bilamellar 5 mm incision height and 
Trabut.  
3) Compare the frequency of moderate/severe eyelid contour abnormalities at one 
year between surgeries performed with bilamellar 5 mm incision height and 
Trabut.  
 
 
3.2 
Study Outcome Measures 
Post-operative Trichiasis 
We will evaluate post-operative trichiasis at 4 time points after surgery: 2 weeks, 6 
weeks,12 months and 3 years. Patient examiners standardized against Dr. Shannath 
Merbs or Dr. Alemayehu Sisay will perform the assessments.  The assessment is made 
by looking at the eyelid with the eye in primary gaze.  Any eyelashes touching the eye 
with the eye in primary gaze are considered to be trichiatic.  Presence of post-operative 
trichiasis (primary outcome) is defined as 1+ trichiatic eyelashes or evidence of recent 
epilation.  If an eyelid has trichiasis at 2 weeks but not at a later point, the eyelid will be 
considered not to have post-operative trichiasis.  

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
13 
 
Eyelid Contour Abnormalities 
We will evaluate eyelid contour abnormalities at each post-operative visit.   The 
examiner will grade the presence of abnormality using the definition provided below in 
the statistical considerations chapter. Both field and photographic grades will be utilized. 
The field grade will serve as the primary grade for the primary study analyses; 
secondary analyses will utilize the photograph grade.  Examiners will be standardized at 
the start of the 6-week visits.  
Pyogenic Granuloma 
Pyogenic granulomas occasionally develop after trichiasis surgery, and it is thought that 
these are a response to a foreign body, such as suture material or a jagged incision 
edge.  The patient examiners will evaluate presence of granulomas at 6 weeks, 12 
months, and 3 years (with primary outcome being granuloma formation by the 12-18 
month visit).  All granulomas will be noted, regardless of size.  
 
 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
14 
 
4 STUDY ENROLLMENT AND WITHDRAWAL 
Study participants will be recruited from patients presenting for trichiasis surgery in the 
Hadiya Zone, in southern Ethiopia.  We will not exclude subjects based on race or 
gender; however, participants must be aged 18 or older.    
4.1 
Subject Inclusion Criteria 
In order to be eligible to participate in this study, an individual must meet all of the 
following criteria: 
• Aged 18 or older 
• At least one eyelid with previously unoperated upper eyelid trichiasis  
• Willing to comply with all study procedures and be available for the duration of 
the study  
4.2 
Subject Exclusion Criteria 
An individual who meets any of the following criteria will be excluded from participation 
in this study: 
• Inability to provide independent, informed consent 
• All eyes with previously unoperated trichiasis are phthisical 
4.3 
Strategies for Recruitment and Retention 
Subjects will be recruited on the day that they present for trichiasis surgery.  We will 
collaborate with an ongoing surgical program in the area (Orbis International) and will 
assist them with identifying patients with trichiasis.  Advance screening will be 
conducted by the Orbis team.  All individuals with trichiasis who would like to have 
surgery will be scheduled for surgery within 2-4 weeks after screening.  On the day of 
surgery, they will be told about the study and anyone interested in learning more will 
meet with a consent specialist to hear a full description of the study and to complete the 
consent process if eligible and interested.  All trichiasis patients will receive surgery free 
of charge, regardless of participation in the trial.   
Subjects will not receive compensation for participation.  Participant retention is 
maintained through contact with a local community health worker, who lives in the 
village with the participants and has a long-term relationship with them.  The project 
director will call community health workers approximately 2 weeks before upcoming 
study visits to remind them that they need to contact the subjects living in their village to 
bring them for the follow up visit. Also, during the surgery day and at each follow up, 
patients will receive reminder cards stating the date and location of the next follow up 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
15 
 
visit.  This approach has been extremely successful in our previous trials, with retention 
rates of over 95% of eligible subjects.  
4.4 
Treatment Assignment Procedures 
4.4.1 
Randomization Procedures  
Participants will be randomized at the participant level to one of three arms: 1) BLTR 
with target incision height of 3 mm 2) BLTR with target incision height of 5 mm and 3) 
Trabut with target incision height of 3 mm.  Both eyes will be operated with the same 
surgical procedure and incision height if both eyes need surgery.   Randomization 
assignments will be prepared in individual opaque envelopes with the patient ID number 
on both the outside of the envelope and on the internal papers indicating the arm 
assigned. The envelope will be opened during enrollment by the Program Manager. The 
surgeon and surgical assistant will both confirm the assigned surgical procedure and 
incision height at the start of the procedure. They will be required to indicate the 
assigned procedure and height on the surgical evaluation form and to measure and 
record the actual height of the incision made. Incision heights will be measured for 
patients in all three randomization arms. 
The randomization assignments will be developed at UNC.  Each week reported 
assigned surgical procedures and incision heights will be compared against the master 
table to ensure the assigned procedure and heights are consistently being reported for 
each participant. Details on monitoring are available in the quality assurance section. 
4.4.2 
Masking Procedures 
The study subject and the outcomes assessment team will be masked to treatment 
assignment.  However, the surgeon will not be masked to the treatment assignment 
since s/he must know what procedure to perform and what height to make the incision 
at.  In order to ensure the outcomes assessors remain masked, they will not be present 
at the surgical site, and they will not have access to data from the baseline and surgical 
visit.   
4.5 
Subject Withdrawal 
Subjects may withdraw voluntarily from the study at any time.  Because the intervention 
is a one-time intervention, the investigators should not have reason to withdraw a study 
subject for non-compliance.   

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
16 
 
5 STUDY INTERVENTION 
In this trial, all subjects will receive trichiasis surgery using the BLTR or Trabut 
procedure.  The primary study intervention is surgical procedure, with either Trabut or 
BLTR with 3 mm or 5 mm from the eyelid margin.  
5.1 
Study Procedural Intervention Description 
Surgeons will receive the surgical procedure and incision height assignment just prior to 
surgery for that participant.  Immediately before beginning surgery, the surgeon will 
confirm with the surgical assistant what the procedure is (BLTR or Trabut) and if BLTR, 
what the assigned target incision height is.  
5.2 
Procedures for Training of Clinicians on Procedural Intervention 
Prior to recruitment, each study surgeon must be certified using the World Health 
Organization’s checklist for final assessment of surgeons by an external evaluator (Dr. 
Amir Bedri Kello, Alemayehu Sisay or Dr. Demissie Tadesse) to ensure s/he 
consistently performs high-quality surgery following the World Health Organization’s 
recommended procedure.  Then the surgeon will be trained by the study oculoplastic 
surgeon, Dr. Shannath Merbs, on how to appropriately indicate where to make the 
incision and then to measure the incision after making it.   
Target incision heights will be indicated using a sterile surgical marker.  Each study 
surgeon will receive extensive practice in measuring the distance from the eyelid margin 
with calipers and marking the location of the incision across the length of the eyelid.  We 
will utilize our surgical simulation device, HEAD START, to practice measuring and 
marking the incision height.  Once surgeons are comfortable with the approach, we will 
prepare a series of incised eyelids (on HEAD START) and will ask the surgeons to 
measure the height of each incision nasally, centrally, and temporally.  Once they reach 
a kappa of >0.7 for measuring the heights compared to Dr. Merbs measurements, we 
will proceed to similar practice with live patients.  Again, kappas of >0.7 for measuring 
the height of the incision will be required before the surgeon is able to work 
independently.  
Monthly throughout the enrollment and surgery phase of the trial, one of the study 
ophthalmologists (Dr. Bedri, Dr. Alemayehu and Dr. Demissie) will visit the surgery team 
and will assess surgical measurements.   
 
 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
17 
 
5.3 
Assessment of Clinician and/or Subject Compliance with Study 
Procedural Intervention 
The Project Director will regularly monitor surgical activities in-person to ensure that the 
surgeons are following the study procedures, performing the correct procedure, and 
accurately measuring and recording the incision height.  Each week the Coordinating 
Center (CC) will compare the assignment reported on the Surgical Evaluation form 
against the actual assignment.  The CC will issue a query for each instance where there 
is any disagreement between the recorded assignment and actual assignment. The CC 
will also compare the reported assigned height on the Surgical Evaluation against the 
actual height measurements.  Frequency of differences greater than 0.5mm will be 
reported at the surgeon level on a cumulative basis. Whenever more than 5% of the 
actual measurements are more than 0.5 mm different than the assigned measurements, 
the surgeon will be reevaluated by one of the study ophthalmologists to determine what 
corrective measures need to be made.  
 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
18 
 
6 STUDY SCHEDULE 
Visit Type 
Timing 
Window 
Eligibility Screening 
Day 0 
N/a (potential subjects to be 
screened for eligibility when 
they present for surgery) 
Enrollment and 
Baseline Exam 
Day 0 
N/a (subjects to be enrolled 
right after screening) 
Surgery 
Day 0 
0-14 days after enrollment.  If 
surgery must be delayed more 
than 2 weeks, a new baseline 
exam should be completed. 
1-day post-
operative visit 
Day 1 
Day 1-2 
Suture Removal 
2 weeks after 
surgery 
10 – 18 days after surgery 
6 week follow up 
6 weeks after 
surgery 
5 to 9 weeks post-surgery 
12 month follow up 
12 months after 
surgery 
11 to 18 months post-surgery 
3 year follow up 
3 years after 
surgery 
30 to 42 months post-surgery 
6.1 
Eligibility Screening and Enrollment (Day 0) 
Eligibility screening will take place at trichiasis surgery camps.  Prior to this, local eye 
care workers will have identified all individuals with trichiasis and scheduled them for 
surgery.  When patients present for trichiasis surgery, a trichiasis surgeon or screener 
will screen them for the presence of trichiasis and will note whether prior surgery has 
been performed on any eye that has trichiasis that day.  Then the consent specialists 
will make a general announcement about the study and invite those who would like to 
learn more and possibly participate to meet individually with one of them.   
The consent specialists will meet with trichiasis surgery patients in small groups to tell 
them about the study and then individually will assess eligibility using the Eligibility 
Review form.  If they are eligible and interested in participating, the consent specialist 
will proceed to obtain informed consent with one patient at a time.  The full process for 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
19 
 
obtaining informed consent is provided in the Manual of Procedures.  Those who 
provide consent will then meet with the project manager to be enrolled in the study.         
Required Procedures/Data Collection: 
• Complete Eligibility Screening form (Form 1) 
• Obtain informed consent 
• Collect Demographic and Tracking Information 
6.2 
Baseline Ocular Exam and Surgery (Day 0) 
The baseline exam occurs immediately after enrollment and just prior to surgery (all 
happen on the same day).  The goal of this exam is to characterize trichiasis severity 
and visual acuity prior to surgery.  Baseline trichiasis severity is an important predictor 
of post-operative trichiasis; hence, these data will be included in all models evaluating 
the outcome.  
After the ocular exam, the patient receives trichiasis surgery.  
Required Data Collection: 
• Baseline Ocular Exam Form 
• Surgical Evaluation Form 
6.3 
Follow up Visits 
Follow up visits occur 1 day, 2 weeks, 6 weeks,12 months and 3 years following 
surgery.  At the 2 week visit, sutures are removed.  At each follow up visit the patient 
examiner evaluates each eyelid for the presence of trichiasis, eyelid contour 
abnormality and granuloma.  At the one-day post-operative visit, the examiner checks 
the status of the surgery.  If eyelashes are touching the eye or if the eyelid is completely 
flipped (gross over-correction) then the surgeon should adjust the surgery to correct the 
eyelid.  
Required Procedures/Data Collection: 
• Follow up visit form (2 week, 6 week, 12 month or 3 year form) 
• Adverse Event Form (if applicable) 
6.4 
Unscheduled Visit 
Between visits, the primary point of contact between subjects and the study team 
typically will be the community health worker (CHW) living in their community.  Subjects 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
20 
 
who experience problems between study visits will meet with the CHW who will assess 
the issue and determine whether a study team member should come to the village for 
an unscheduled study visit or whether the CHW can resolve the issue himself.  If such a 
visit is necessary, the study team member will visit the subject and will complete an 
Unscheduled Visit form to document the purpose of the visit and what procedures, if 
any, were performed.  If the CHW and study team member determine that a study visit 
is not required, the study team member simply needs to complete the CHW/Participant 
Call Log, indicating the date of the call, participant ID, reason for call and actions taken. 
Required Procedures/Data Collection: 
• CHW Participant Call Record 
• Unscheduled Visit Form  

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
21 
 
 
6.5 
Timeline and Feasibility of Adhering to Study Schedule 
The study recruitment and follow up schedule is outlined in the table below. 
 
Year 1  
(Mar 2016 – Feb 2017) 
Year 2  
(Mar 2017 – Feb 2018) 
Year 3  
(Mar 2018 – Feb 2019) 
Year 4  
(Mar 2019 – Feb 2020) 
Activity 
Q1 
(Mar-
May) 
Q2 
(Jun-
Aug) 
Q3 
(Sep- 
Nov) 
Q4 
(Dec-
Feb) 
Q1 
(Mar-
May) 
Q2 
(Jun 
-
Aug) 
Q3 
(Sep- 
Nov) 
Q4 
(Dec-
Feb) 
Q1 
(Mar-
May) 
Q2 
(Jun 
-
Aug) 
Q3 
(Sep- 
Nov) 
Q4 
(Dec-
Feb) 
Q1 
(Mar-
May) 
Q2 
(Jun 
-
Aug) 
Q3 
(Sep- 
Nov) 
Q4 
(Dec-
Feb) 
Ethics Applications 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Recruitment/Enrollment 
 
 
 
Start 
Jan 
 
 
 
 
End 
Mar 
or 
Apr* 
 
Start 
Oct 
X 
End 
Mar 
 
 
 
2 and 6-week follow up 
 
 
 
X 
 
 
 
 
X 
X 
X 
X 
End 
May 
 
 
 
1 year follow up 
 
 
 
 
X 
 
 
 
 
 
 
Start 
Jan 
X 
 
Start 
Oct 
X 
Data cleaning 
 
 
 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Dissemination of Study 
Findings (manuscripts 
and presentations) 
 
 
 
 
 
X 
X 
X 
 
 
 
 
 
 
 
 
*Depends on when the rains start. 
 
 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
22 
 
 
Year 5  
(Mar 2020 – Feb 2021) 
Year 6  
(Mar 2021 – Feb 2022) 
Year 7 (partial)  
(Mar 2022 – 
July 2022) 
Activity 
Q1 
(Mar-
May) 
Q2 
(Jun-
Aug) 
Q3 
(Sep- 
Nov) 
Q4 
(Dec-
Feb) 
Q1 
(Mar-
May) 
Q2 
(Jun -
Aug) 
Q3 
(Sep- 
Nov) 
Q4 
(Dec-
Feb) 
Q1 
(Mar-
May) 
Q2 
(Jun -
Aug) 
1 year follow up 
Planned 
but 
didn’t 
happen 
 
 
 
 
 
 
 
 
 
3 year follow up 
 
 
 
X 
X 
 
X 
X 
X 
 
Data cleaning 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Dissemination of Study 
Findings (manuscripts and 
presentations) 
 
 
 
 
 
 
 
X 
X 
X 
 
 
 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
23 
 
7 STUDY PROCEDURES / EVALUATIONS 
Detailed methods for data collection for each of the study procedures are provided in 
the Manual of Procedures.  This section lists the procedures and describes the general 
approach for data collection. 
Ocular Examination: At baseline, the ocular exam will consist of an evaluation of each 
eyelid for the presence of trichiasis and presence of corneal opacity.  At each follow up 
study visit, both eyelids will be assessed for the presence of trichiasis, eyelid contour 
abnormality and granuloma.   
Visual Acuity:  Visual acuity will be assessed monocularly at baseline (pre-operatively) 
and 12 months postoperatively using an Early Treatment of Diabetic Retinopathy 
(ETDRS) tumbling “E” chart on a smartphone.   
Trichiasis Surgery: All participants will receive trichiasis surgery with either the BLTR or 
Trabut procedure outlined in the World Health Organization’s Trichiasis Surgery 
Manual, with exception of the incision placement for ½ of the BLTR surgeries.  In the 
trial, BLTR incisions will be placed 3 mm or 5 mm away from the eyelid margin, 
depending on randomization assignment.  Detailed methods for how to measure and 
mark where to make the incision are provided in the Manual of Procedures. 
Photographs: Photographs will be taken of each eyelid preoperatively, during surgery 
after incision is made, immediately postoperatively, and at each follow up visit.  
 
 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
24 
 
8 PROVISIONS FOR MONITORING STUDY PROGRESS 
Multiple levels of oversight have been built into the trial to ensure patient safety and 
data integrity.  These include: 
Internal Monitoring: 
• Weekly monitoring of accumulating data to ensure complete data collection 
• Weekly assessment of compliance with assignment of surgical procedure and 
incision height 
• Regular field monitoring by local and international team members 
• Active collection of adverse events during surgery and at each follow up visit. 
In addition, we will follow UNCs guidelines for reporting all safety events. 
External Monitoring: 
• An NEI-designated Data and Safety Monitoring Board 
• Annual reports to the Institutional Review Boards at each institution and to the 
Ethiopian ethics board (National Health Research Ethics Review Committee, 
Ministry of Science and Technology).  
Detailed information on the managing guidelines and approaches for each of 
these is provided in the Manual of Procedures.   
 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
25 
 
9 STATISTICAL CONSIDERATIONS 
9.1 
Study Hypotheses 
Primary Aims: 
Primary study null hypotheses:  
1) Among BLTR surgeries, increasing the target incision height from 3 mm to 
5 mm will not affect the rate of post-operative trichiasis (PTT).  
2) BLTR surgery with a target incision height of 3 mm will have the same rate 
of post-operative trichiasis as Trabut surgery.  
3) BLTR surgery with a target incision height of 5 mm will have the same rate 
of post-operative trichiasis as Trabut surgery.  
Alternative hypotheses:   
1) Among BLTR surgeries, increasing the target incision height from 3 mm to 
5 mm will result in a 25% reduction in the rate of post-operative trichiasis 
(PTT).  
2) Trabut surgery will result in a 25% reduction in the rate of post-operative 
trichiasis compared to BLTR surgery with a 3 mm target incision height.  
3) Trabut surgery will result in a 25% reduction in the rate of post-operative 
trichiasis compared to BLTR surgery with a 5 mm target incision height.  
Secondary Aims: 
Null hypothesis:  
1) Among BLTR surgeries, increasing the target incision height from 3 mm to 
5 mm will not affect the rate of eyelid contour abnormalities.  
2) Eyelids operated with Trabut will have the same rate of moderate/severe 
eyelid contour abnormalities rate as eyes operated with BLTR with a 
target incision height of 3 mm.  
3) Eyelids operated with Trabut will have the same rate of moderate/severe 
eyelid contour abnormalities rate as eyes operated with BLTR with a 
target incision height of 5 mm.  
4) Eyelids operated with Trabut will have the same rate of granuloma 
formation as eyelids operated with BLTR.  

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
26 
 
Alternative hypotheses:   
1) Eyelids operated with the BLTR surgery and 3 mm will have fewer eyelid 
contour abnormalities than eyelids operated with Trabut.  
2) Eyelids operated with Trabut will have a higher rate of moderate/severe 
eyelid contour abnormalities rate than eyes operated with BLTR with a 
target incision height of 3 mm.  
3) Eyelids operated with Trabut will have a higher rate of moderate/severe 
eyelid contour abnormalities rate than eyes operated with BLTR with a 
target incision height of 5 mm.  
4) Eyelids operated with Trabut will have a lower rate of granuloma formation 
than eyelids operated with BLTR.  
9.2 
Sample Size Considerations 
The planned sample size for this trial is 4,953 participants.  This sample size will give 
sufficient power to detect a 25% difference in post-operative trichiasis rates between 3 
mm and 5 mm target incision heights for BLTR, a 25% difference in post-operative 
trichiasis rates for BLTR 3 mm versus Trabut and a difference of 25% between BLTR 5 
mm and Trabut.  This estimate is based on the following assumptions: 
• 15% of eyelids in the BLTR 3 mm target height group will develop post-operative 
trichiasis during the 12 months following surgery 
• Two-sided alpha error = 5% 
• Power = 80% 
• 40% of participants will have 2 eligible eyes 
• The correlation between 2 eyes of an individual is 0.24 
• 5% loss to follow up. 
Based on these assumptions, the table below shows the total number of participants 
needed within the 3 arms combined.  
Prevalenc
e in 
control 
group 
RR 
Subject
s per 
Arm 
Total 
number 
of 
subjects 
In the 3 
arms  if 
100% 
bilateral 
Total 
number 
of 
surgerie
s 
needed 
Only 40 
% of 
surgeries 
will be 
bilateral 
# of 
surgeries 
Additional 
Subjects 
(surgeries) 
to accrue 
the total 
number 
needed 
Total 
number 
of 
subject
s to be 
enrolled 
Increase 
to 
account 
for  5% 
lost to 
follow-up 
15% 
0.70 
743 
2229 
4458 
3121 
955 (1337) 
3184 
3351 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
27 
 
16% 
0.70 
690 
2070 
4140 
2898 
887 (1242) 
2957 
3112 
15% 
0.75 
1098 
3294 
6588 
4612 
1411 
(1976) 
4705 
4953 
16% 
0.75 
1019 
3057 
6114 
4280 
1310 
(1834) 
4367 
4597 
 
9.3 
Analysis Plan 
We will follow these general analysis principles: 
• The primary analyses will be performed according to the participant’s assigned 
intervention.  
• All participants who complete randomization and have surgery performed will be 
included in analyses. 
• All events following surgery will be counted.  
• All analyses will be conducted at the eye level, using the generalized estimating 
equations approach to correct standard errors (to account for the correlation 
between two eyes of a subject). 
• Unless otherwise indicated, three sets of analyses will be performed:1) BLTR 3 
mm versus BLTR 5 mm and 2) BLTR 3 mm versus Trabut 3 mm 3) BLTR 5 mm 
versus Trabut 3 mm. 
 
Post-operative Trichiasis Analyses: 
The primary analyses will be based on the dichotomous outcome: presence or 
absence of post-operative trichiasis at any time point within 12-18 months following 
surgery. Both unadjusted and adjusted analyses will be performed.  Adjusted analyses 
will account for the severity of pre-operative trichiasis, with severity defined based on 
the table below.  
 
Trichiasis Severity Classification 
Description 
Mild 
 
1-4 Eyelashes touching globe, no 
epilation  
 
OR 
 
1-10 Eyelashes epilated, no eyelashes 
touching globe 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
28 
 
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 
(Gower et al. 2013. JAMA Ophthalmol.;131(3):294-301.) 
 
Multiple secondary analyses of post-operative trichiasis will be performed.  We will 
compare the severity of post-operative trichiasis between groups, with severity defined 
using the table above.  First, we will compare the primary groups utilizing severity at first 
observation (6 weeks or 12 months for the primary outcome).  Then we will compare 
groups using severity at final observation.   This will allow us to determine whether one 
group has a higher ‘surgical failure’ rate and whether recurrent trichiasis progression 
varies across interventions. We will conduct both unadjusted and adjusted analyses. 
Eyelid Contour Abnormalities: 
Primary analyses of eyelid contour abnormalities will be based on a dichotomous 
variable: presence or absence of moderate/severe contour abnormality at the last study 
visit where the participant was seen between 6 weeks and 12-18 months, , or at last 
visit before repeat surgery using the photograph grade, which will be based on the 
definitions below.  For the purposes of this analysis, mild will be combined with “no 
abnormality” and moderate and severe will be combined to form the “moderate/severe 
contour abnormality” group.  
 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
29 
 
Abnormality 
Definition 
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  
 
(Gower et al. 2012 PLoS Negl Trop Dis 6(6): e1713)  
 
Secondary analyses will explore the relationship between incision height and the full 
range of eyelid contour abnormalities, which will require use of the photographic grade 
that will be graded centrally.  
 
Targeted versus Actual Incision Height: 
We will conduct an analysis to compare the assigned incision height against the actual 
incision height measured during surgery.  If more than 10% of the heights vary by more 
than 0.5 mm, we will conduct secondary analyses for each of the above analyses to 
determine whether the results of the actual incision height analyses are similar to the 
per-protocol analyses.  If differences exist, we will report these analyses separately, but 
will emphasize that the per-protocol analyses are the primary analyses.  
 
New Versus Conversion Surgeons 
Analyses will also be conducted stratifying based on surgeons’ prior experience.  
Specifically, we will conduct all above analyses based on whether surgeons were 
trained on both bilamellar and Trabut simultaneously, or whether they first learned 
bilamellar and received additional training in Trabut at a later time.  
 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
30 
 
 
 
1-day Surgical Corrections 
Finally, we will conduct an analysis to determine whether there is a difference in the rate 
of 1-day surgical corrections by study arm.  
 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
31 
 
10 QUALITY CONTROL AND QUALITY ASSURANCE 
We will ensure high quality data collection through the course of the trial by ensuring 
adequate training of all staff on human subjects research and their roles in the trial.  All 
staff must be certified in their respective roles by the project leaders before interacting 
with study participants and handling study-related data. 
10.1 
Training 
All personnel will undergo extensive training to ensure consistency in data-collection 
procedures. We will begin with an ethics training session for all study staff, and ethics 
certification will be required from each staff member before the study begins.  We will 
then provide an overview of the study design, each team member’s responsibilities, and 
how members integrate to form a cohesive data-collection team.  Then, a two-day 
training session will be held for each data-collection group to ensure they understand 
forms completion and the details of the data that they are supposed to collect.    
The recruitment team, surgical assistants, and study coordinators will be trained on 
appropriate methods for conducting in-person interviews and use of the data-collection 
forms.  Training for all personnel will include didactic instruction and clinical 
demonstration with live subjects.  Upon completion of training, all personnel will be 
evaluated for all procedures that they will be asked to perform. Only those who pass 
certification will continue with the study team.   
An independent evaluator will critically examine all surgeons to ensure that they perform 
high-quality surgery and follow recommended WHO procedures.  Each surgeon will be 
evaluated using the WHO certification checklist and only certified surgeons will be 
allowed to participate in the study.  Dr. Merbs will train the surgeons on how to 
consistently measure incision heights and incision lengths.  We will require kappas>0.7 
for each measurement comparing the individual surgeon to Dr. Merbs before the 
surgeon will be considered proficient in collecting these measures.  
The outcomes examiner will be trained on how to grade trichiasis and eyelid contour 
abnormalities using photographs and actual trichiasis patients. Kappas of 0.7 will be 
required before the examiner is certified.  In the second year of the trial, recertification 
for all patient examiners will be held at the start of the second series of surgical camps 
and 12-month follow ups.    
10.2 
Quality Monitoring 
To ensure data integrity and study participants’ safety, our plan for data and safety 
monitoring involves several levels.  The first level is the extensive set of data-
management activities (see Protocol and Manual of Procedures) to help ensure data 
integrity.  These include daily field-based review of data collection to ensure 
completeness and accuracy before submitting the data to the data entry team, 
redundant systems to check randomization schemes, double data-entry practices, and 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
32 
 
continuous data-quality monitoring through generation of regular reports.  These reports 
are reviewed by the data manager to initiate data cleaning operations, and by the 
Principal Investigator, who may initiate re-training exercises or change supervisory 
practices as needed.  
The second level of monitoring includes regular site visits by our senior study team 
members.  Our team of experts will ensure all staff members are proficient in necessary 
procedures before the study begins.  During recruitment, Drs. Bedri and Alemayehu will 
alternate making monthly visits to the study team to monitor surgical procedures and 
correct any drift or modifications that have inadvertently arisen.  At the start of the 6-
week and 12-month visits, Dr. Merbs will return to Ethiopia to evaluate the outcomes 
assessor and ensure kappas are at least 0.7 for key outcomes (PTT and ECA). Dr. 
Gower also will visit Ethiopia at the start of 12-month data collection to provide refresher 
training to all study team members and to monitor data-collection procedures.    
10.3 
Data and Safety Monitoring Board 
With input from NIH, we will assemble a data and safety monitoring board (DSMB) to 
oversee the study.  At a minimum, the committee will consist of a trialist, a statistician, 
and content experts, including someone with local cultural expertise.  We will plan for 
one DSMB meeting prior to study initiation, and then in-person meetings annually, with 
at least one scheduled teleconference between in-person meetings, and more as 
needed or desired by the DSMB.  We will prepare summary reports of accumulated 
data for each meeting. 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
33 
 
11 ETHICS/PROTECTION OF HUMAN SUBJECTS 
11.1 
Ethical Standards 
The investigators will ensure that this study is conducted in full conformity with the 
principles set forth in the Declaration of Helsinki and The Belmont Report: Ethical 
Principles and Guidelines for the Protection of Human Subjects of Research, as drafted 
by the US National Commission for the Protection of Human Subjects of Biomedical and 
Behavioral Research (April 18, 1979) and codified in 45 CFR Part 46 and/or the ICH E6.  
11.2 
Institutional Review Board 
The protocol, informed consent form(s), recruitment materials, and all subject materials 
will be submitted to the Wake Forest, University of North Carolina, and Johns Hopkins 
IRBs as well as the National Health Research Ethics Review Committee, Ministry of 
Science and Technology, Ethiopia for review and approval.  Approval of both the 
protocol and the consent form must be obtained before any subject is enrolled.  Any 
amendment to the protocol will require review and approval by the IRB before the 
changes are implemented in the study.   
11.3 
Informed Consent Process 
Informed consent is a process that is initiated prior to the individual agreeing to 
participate in the study and continues throughout study participation.  Extensive 
discussion of risks and possible benefits of study participation will be provided to 
subjects and their families, if applicable.  A consent form written in Amharic and 
describing in detail the study procedures and risks will be given to the subject.  Consent 
forms will be IRB-approved, and the subject is required to read and review the 
document or have the document read to him or her.  The investigator or designee will 
explain the research study to the subject and answer any questions that may arise.  The 
subject will sign (typically through providing a fingerprint) the informed consent 
document prior to any study-related assessments or procedures.  Subjects will be given 
the opportunity to discuss the study with their surrogates or think about it prior to 
agreeing to participate.  They may withdraw consent at any time throughout the course 
of the study.  A copy of the signed informed consent document will be given to subjects 
for their records.  The rights and welfare of the subjects will be protected by 
emphasizing to them that the quality of their clinical care will not be adversely affected if 
they decline to participate in this study. 
The consent process will be documented in the research record.   
11.4 
Exclusion of Women, Minorities, and Children (Special Populations) 
We will not limit enrollment based on sex or racial/ethnic background.  Children will not 
be enrolled in the clinical trial because trichiasis is uncommon in this age range, and 
general anesthesia is required for trichiasis surgery on children.  Children with trichiasis 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
34 
 
will be referred to the nearest location that can safely provide the necessary surgical 
services.  
11.5 
Subject Confidentiality 
All patient data will be kept secure at all times.  Paper-based forms will be stored in 
locked file cabinets and access will be limited to those who have a specific need to 
review patient-level information.  All study computers will be encrypted following the 
UNC guidelines and will require passwords for logon to the computer, with a separate 
password to access the study database.   
 
 
 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
35 
 
12 COMMUNITY INVOLVEMENT PLAN 
This project will be conducted in Hadiya, SNNPR.  The project will actively involve 
members of the community in several ways.  First, we will utilize community members 
such as trained community based screeners (Eye Ambassadors) to identify potential 
trial participants.  Additionally, during the recruitment and surgery phase of the trial we 
will employ several individuals from the SNNPR region and provide them with on-the-job 
training that will provide long-term skills development for them. Specific skill sets that we 
will develop in the staff are how to conduct clinical research, how to properly collect 
data, and how to utilize a computer for data entry and management (specifically MS 
Access).  Field staff will be taught how to evaluate trichiasis and how to be a surgical 
assistant (preparing equipment, recording data, etc).  We will also utilize local staff to 
serve as the follow up evaluators for 18 months following the start of recruitment.  
Community members with trichiasis may also benefit by taking part in the clinical trial 
(receiving trichiasis surgery) itself.  These individuals will be followed regularly in their 
communities, which should allow them to be able to be monitored closely and to quickly 
identify any additional trichiasis management needed.  
 
 
 
 
 

 
Version 2.4 
Maximizing Trichiasis Surgery Success Trial 
10 October 2021 
 ________________________________________________________________________________________________________  
 
 _____________________________________________________________________________________________  
 
36 
 
13 PUBLICATION/DATA SHARING POLICY 
The Executive Committee will be responsible for developing publication procedures and 
resolving authorship issues.  At the start of the trial, the committee will outline the 
expected primary papers for the trial, and will make initial assignments.  As additional 
papers are identified through the course of the trial, authorship will be discussed at the 
next Executive Committee meeting.  This procedure was followed in our most recent 
trial, and the investigative team (who comprise the majority of the current team) was 
happy with this approach. Because the scientific team is relatively small compared with 
other clinical trials, it is anticipated that all publications will follow traditional authorship 
instead of corporate or modified corporate authorship.   
This study will comply with the NIH Public Access Policy, which ensures that the public 
has access to the published results of NIH funded research. It requires scientists to 
submit final peer-reviewed journal manuscripts that arise from NIH funds to the digital 
archive PubMed Central upon acceptance for publication. 
The International Committee of Medical Journal Editors (ICMJE) member journals have 
adopted a clinical trials registration policy as a condition for publication.  The ICMJE 
defines a clinical trial as any research project that prospectively assigns human subjects 
to intervention or concurrent comparison or control groups to study the cause-and-effect 
relationship between a medical intervention and a health outcome.  Medical 
interventions include drugs, surgical procedures, devices, behavioral treatments, 
process-of-care changes, and the like.  Health outcomes include any biomedical or 
health-related measures obtained in patients or participants, including pharmacokinetic 
measures and adverse events. The ICMJE policy requires that all clinical trials be 
registered in a public trials registry such as ClinicalTrials.gov, which is sponsored by the 
National Library of Medicine.  This study will be registered in ClinicalTrials.gov. 
 
The trial investigators fully support the dissemination of data from this clinical trial.  In 
accordance with NIH policies, we will prepare a de-identified dataset for public use.  The 
de-identified data, study protocol and annotated case report forms will be available 
through a website hosted by the University of North Carolina, and data release will 
coincide with publication of the primary and pre-planned secondary results, estimated to 
be completed in 2020.  Photographic images of study eyelids will not be shared on the 
website, as these cannot be completely de-identified. Hence, photographic images will 
be made available through formal requests from researchers to the University of North 
Carolina.  Researchers requesting these images will be required to sign a data use 
agreement adhering to the School’s and NIH’s requirements for maintaining strict 
confidentiality of all images.