Trichiasis
Conditions
Keywords
trichiasis, azithromycin, trichiasis surgery, topical tetracycline
Brief summary
Trachoma, an ocular infection caused by C. trachomatis, is the second leading 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 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 correct trichiasis. Despite this encouraging news, under the best of circumstances the recurrence rate of trichiasis following surgery is disappointingly high. The objective of our project is to conduct a randomized, controlled clinical trial of post-surgical antibiotic treatment, comparing oral azithromycin to topical tetracycline, for trichiasis surgical patients in Ethiopia with the goal of determining the impact of treatment on rates of trichiasis recurrence at one and two years.
Detailed description
A randomized clinical trial of the effectiveness of a single dose of azithromycin compared to 6 weeks of topical tetracycline, and the added benefit of family-based azithromycin treatment, in preventing recurrence of trichiasis following surgery is proposed. This will provide the evidence base to inform and change the global public health policy and the donation program policy, regarding post-surgical treatment for trichiasis patients and possibly their families. The investigators will determine the impact of three treatment strategies following trichiasis surgery on the rate of trichiasis recurrence in the operated eye at six months and one year. A randomized clinical trial of 1425 trichiasis surgical patients will be conducted in Sodo,Ethiopia. The first group (Control Group) will receive topical tetracycline following surgery; the second group (Intervention Patient Group) will receive oral azithromycin; the third group (Intervention Family Group) will receive oral azithromycin, and all family members resident in the patient's household will also receive oral azithromycin. Data will be collected at baseline (pre-surgery) on ocular status and infection status. Data will be collected at the time of surgery on surgery-related variables and surgical and post-operative complications. Additional data will be collected on any surgical complications and early recurrence at the two-week visit when sutures will be removed. A follow up visit at two months will include data collection on recurrence and presence of ocular infection. Evaluations for trichiasis recurrence will occur again at six months and at one year post-surgery. The latter visit will also include data collection on presence of ocular infection in the surgical case, and ocular infection in household members. Evaluation of the risk of recurrence at six months and one, two, and three years within each group will be completed to determine the benefit of using azithromycin compared to topical tetracycline, and the added benefit of family-based treatment.
Interventions
DRUGazithromycin
oral antibiotic
DRUGtopical tetracycline
Sponsors
National Eye Institute (NEI)
Project ORBIS
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Presence of trichiasis: * no previous report of trichiasis surgery in at least one eye with trichiasis: * Agreement by at least one other family member accompanying the patient that, if the patient is randomized to the family-treatment arm, s/he also would be willing to receive antibiotic treatment * Age 18 or older
Exclusion criteria
* other household members concurrently participating in the trial * Self-reported pregnancy * Documented allergy to tetracycline * Plans to move out of the region within 1 year.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrent Trichiasis in Tetracycline and Azithromycin Groups | Primary outcome assessed at 2 weeks,1.5 months, 6 months and 12 months post-surgery | Recurrence of trichiasis : Clinical assessment was done by looking for one or more eye lashes touching globe or evidence of epilation. |
| Recurrent Trichiasis Between Two Azithromycin Arms | Primary outcome assessed at 2 weeks,1.5 months, 6 months and 12 months post-surgery | Recurrence of trichiasis :Clinical assessment for recurrence was done by looking for one or more eye lashes touching globe or evidence of epilation. If there was evidence of epilation or if one or more eye lashes were touching the globe, it was considered as recurrence of trichiasis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Surgical Failure | 6 weeks | The surgery was considered a failure if one or more eye lashes were touching the globe of the eye of the subject. |
| Adverse Events | 6 weeks | At 6 weeks participants/family members were asked about any hospitalization,death,ocular complaints, gastrointestinal illness or other specific illness or any clinic visit within six weeks of receiving surgery. |
Countries
United States
Participant flow
Recruitment details
Patients were randomly assigned initially to receive single dose of oral azithromycin to subject or single dose of azithromycin to subject & immediate family members or topical tetracycline ointment to subject groups.1 yr data suggested no difference in outcome between 2 azithromycin arms.These 2 groups were combined into 1 group in final analysis.
Participants by arm
| Arm | Count |
|---|---|
| Control Topical tetracycline ointment to subject. Antibiotic: Topical tetracycline ointment administered twice daily for for 6 weeks | 484 |
| Intervention1 Oral azithromycin,single 1g dose to subject Antibiotic : Oral azithromycin (1 g) | 483 |
| Intervention2 Oral azithromycin,single 1g dose to subject and immediate family members Antibiotic : Oral azithromycin (1 g) | 485 |
| Total | 1,452 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| 12 Month Follow-up | Death | 3 | 4 | 4 |
| 12 Month Follow-up | Lost to Follow-up | 7 | 6 | 6 |
| 12 Month Follow-up | Reached endpoint | 13 | 6 | 9 |
| 1.5 Month Follow-up | Death | 2 | 0 | 0 |
| 1.5 Month Follow-up | reached the endpoint | 12 | 8 | 12 |
| 6 Month Follow-up | Death | 2 | 1 | 3 |
| 6 Month Follow-up | reached endpont | 20 | 12 | 15 |
Baseline characteristics
| Characteristic | Control | Intervention1 | Intervention2 | Total |
|---|---|---|---|---|
| Age, Continuous | 48.0 years STANDARD_DEVIATION 12.8 | 48.5 years STANDARD_DEVIATION 13 | 50.0 years STANDARD_DEVIATION 12.6 | 48.9 years STANDARD_DEVIATION 13 |
| Region of Enrollment Ethiopia | 484 Participants | 483 Participants | 485 Participants | 1452 Participants |
| Sex: Female, Male Female | 390 Participants | 366 Participants | 365 Participants | 1121 Participants |
| Sex: Female, Male Male | 94 Participants | 117 Participants | 120 Participants | 331 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 484 | 0 / 968 |
| other Total, other adverse events | 13 / 484 | 28 / 968 |
| serious Total, serious adverse events | 0 / 484 | 0 / 968 |
Outcome results
Primary
Recurrent Trichiasis Between Two Azithromycin Arms
Recurrence of trichiasis :Clinical assessment for recurrence was done by looking for one or more eye lashes touching globe or evidence of epilation. If there was evidence of epilation or if one or more eye lashes were touching the globe, it was considered as recurrence of trichiasis.
Time frame: Primary outcome assessed at 2 weeks,1.5 months, 6 months and 12 months post-surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Recurrent Trichiasis Between Two Azithromycin Arms | 26 Participants |
| Intervention | Recurrent Trichiasis Between Two Azithromycin Arms | 36 Participants |
Comparison: We tried to evaluate if treating the immediate family members of the subject with oral azithromycin along with the subject had added advantage in reducing the rate of recurrent trichiasis in comparison to treating the subject alone with oral azithromycin post surgery.~The log rank test was done to compare the survival rates between the two intervention arms.The comparison results were expressed in person-years.p-value: 0.19Log Rank
Primary
Recurrent Trichiasis in Tetracycline and Azithromycin Groups
Recurrence of trichiasis : Clinical assessment was done by looking for one or more eye lashes touching globe or evidence of epilation.
Time frame: Primary outcome assessed at 2 weeks,1.5 months, 6 months and 12 months post-surgery
Population: Recurrence rates (expressed as person-years) in the tetracycline arm was compared with the 2 azithromycin arms combined (483+ 485= 968 participants)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Recurrent Trichiasis in Tetracycline and Azithromycin Groups | 45 Participants |
| Intervention | Recurrent Trichiasis in Tetracycline and Azithromycin Groups | 62 Participants |
Comparison: The log rank test was done to compare the survival rates between the tetracycline arm and the azithromycin arms combined.~The Cox proportional hazard model was used to evaluate risk factors and adjust for confounding in predicting recurrence.p-value: 0.04795% CI: [0.45, 0.98]Log Rank
Secondary
Adverse Events
At 6 weeks participants/family members were asked about any hospitalization,death,ocular complaints, gastrointestinal illness or other specific illness or any clinic visit within six weeks of receiving surgery.
Time frame: 6 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control | Adverse Events | Ocular complaints | 7 Participants |
| Control | Adverse Events | Gastrointestinal complaints/other specific illness | 6 Participants |
| Intervention | Adverse Events | Ocular complaints | 6 Participants |
| Intervention | Adverse Events | Gastrointestinal complaints/other specific illness | 22 Participants |
Secondary
Surgical Failure
The surgery was considered a failure if one or more eye lashes were touching the globe of the eye of the subject.
Time frame: 6 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control | Surgical Failure | 12 Participants |
| Intervention | Surgical Failure | 20 Participants |
Comparison: Surgery was considered a failure if there was trichiasis recurrence at 6 week follow-up.95% CI: [0.36, 1.1]Regression, Logistic