Clinical trial NCT01202331: Tripartite International Research for the Elimination of Trachoma
Official title: Tripartite International Research for the Elimination of Trachoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Trachoma
Chlamydia
Keywords: Bacterial Infections
Chlamydia Infections
Eye Diseases
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2010-09-15
Enrollment: 29000
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Mass antimicrobial administrations have been remarkably successful in reducing the prevalence of the ocular strains of Chlamydia that cause trachoma. Repeated distributions progressively lower the prevalence of infection, and in some cases may even result in local elimination. Mass treatments cannot be continued forever, due to concerns about cost and antibiotic resistance. The hope has been that other measures such as latrine construction and hygiene programs would prevent infection from returning. Unfortunately, no non-antibiotic measure has yet demonstrated an effect on infection.

1. We hypothesize that Chlamydial infection will return to communities when treatment ends.
2. We hypothesize that infection will be completely eliminated in all communities treated for seven years.
3. We hypothesize that identifying and treating clinically active cases among preschool aged children will delay or even prevent reemergence at a far lower cost than mass treatment of all individuals.

Detailed description: The proposed study is a group-randomized trial to determine the frequency and treatment target of community-wide mass antibiotic treatment to eliminate trachoma. We will continue to monitor a sub-set of communities from our TANA study, in Goncha Siso Enese district of East Gojam Zone, Ethiopia. Here we evaluate how infection returns when antibiotics are discontinued, whether infection can be predictably eliminated, and whether infection can be prevented from returning with targeted treatment strategies:

Specific Aim 1. To determine whether antibiotics can be stopped after 4 years.

Specific Aim 2. To determine whether infection can be completely eliminated if mass treatments continue for seven years.

Specific Aim 3. To determine whether treatment targeted to pre-school aged children, or to households in which a pre-school aged child has clinically active trachoma, will prevent infection from returning into the community.

Specific Aim 4: To determine whether mass azithromycin distributions reduce visits to local health clinics due to all causes and infectious causes.

Specific Aim 5: To determine whether mass azithromycin distributions result in better growth metrics (weight-for-height, height-for age, weight-for-age, middle upper arm circumference) compared to no treatment.

Specific Aim 6: To determine whether under-5 mortality is lower in communities treated with mass azithromycin compared to no treatment

Specific Aim 7: To determine whether macrolide resistance in Streptococcus pneumoniae, Hameophilus influenzae, and Staphylococcus aureus is more prevalent in communities treated with biannual mass azithromycin compared to communities treated with annual mass azithromycin, and to determine whether targeted azithromycin treatments result in less macrolide resistance compared to mass azithromycin distributions.

Eligibility criteria: Inclusion Criteria:

* All residents residing in the state-teams which are randomly selected for this study.

Exclusion Criteria:

* Pregnant women
* Children under 6 months of age
* All those who are allergic to macrolides or azalides
* Refusal of village chief (for village inclusion), or refusal of parent or guardian (for individual inclusion)

Individuals in these three exclusion criteria will not be given the study antibiotic azithromycin, but offered the current WHO-recommended alternative treatment to azithromycin for active trachoma, which is 1% tetracycline eye ointment, to be used twice a day, topically to both eyes, for six weeks. Note that the exclusion criteria refer to the exclusion to the treatment drug, but not to the monitoring, treatment of trachoma, and examinations.

Primary outcomes:
measure: The average prevalence of ocular chlamydia infection in communities in an arm as determined by pooled NAAT (Nucleic Acid Amplification Test)(at 36 months versus 0 months for Aim 1, at 36 months for Aim 2 and Aim 3)
timeFrame: 36 months
Secondary outcomes:
measure: Clinical active trachoma in community, as determined by the WHO simplified grading system
timeFrame: 36 months
measure: Childhood mortality (6 months -5 years of age), 6-10 years of age, and >10 years
timeFrame: 36 months
measure: Macrolide resistance in pneumococcus, Haemophilus influenzae, and Staphylococcus aureus (% resistance over time, clustered by randomization unit)
timeFrame: 36 months
measure: Anthropometric measurements (weight and height), as outlined by WHO child growth standards (0-5 years of age)
timeFrame: 3, 12, 24, and 36 months after baseline
measure: Health clinic visits (due to all causes and due to infectious causes) in children aged 6 months-5 years, 6-10 years, and >10 years
timeFrame: 36 months
measure: Prevalence of anemia (hemoglobin levels in 0-9 year olds) and the prevalence of malaria
timeFrame: 36 months
measure: Clinically active trachoma in a school (all children under age 10), as determined by the WHO simplified grading system
timeFrame: 36 months
measure: Cost-effectiveness of mass azithromycin administration, per infection year prevented and cost per eliminated village
timeFrame: 0, 12, 24, and 36 months
measure: Estimate of chlamydial load from real-time, qPCR
timeFrame: 0, 12, 24, 36 months
Other outcomes:
Locations:
city: Addis Ababa
country: Ethiopia
facility: The Carter Center, Ethiopia
Study officials:
affiliation: F.I. Proctor Foundation, UCSF
name: Tom Lietman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: F.I. Proctor Foundation, UCSF
name: Kieran S O'Brien, MPH
role: STUDY_DIRECTOR
affiliation: Emory University
name: Paul Emerson, PhD
role: STUDY_DIRECTOR
References:
citation: Keenan JD, Gebresillasie S, Stoller NE, Haile BA, Tadesse Z, Cotter SY, Ray KJ, Aiemjoy K, Porco TC, Callahan EK, Emerson PM, Lietman TM. Linear growth in preschool children treated with mass azithromycin distributions for trachoma: A cluster-randomized trial. PLoS Negl Trop Dis. 2019 Jun 5;13(6):e0007442. doi: 10.1371/journal.pntd.0007442. eCollection 2019 Jun.
citation: Keenan JD, Tadesse Z, Gebresillasie S, Shiferaw A, Zerihun M, Emerson PM, Callahan K, Cotter SY, Stoller NE, Porco TC, Oldenburg CE, Lietman TM. Mass azithromycin distribution for hyperendemic trachoma following a cluster-randomized trial: A continuation study of randomly reassigned subclusters (TANA II). PLoS Med. 2018 Aug 14;15(8):e1002633. doi: 10.1371/journal.pmed.1002633. eCollection 2018 Aug.