Clinical trial NCT02754583: Sanitation, Water, and Instruction in Face-washing for Trachoma I/II
Official title: Sanitation, Water, and Instruction in Face-washing for Trachoma I/II
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Trachoma
Keywords: trachoma
soil transmitted helminths
sanitation
face washing
antibiotics
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: The Carter Center
name: Amhara Public Health Institute
name: Emory University
name: National Eye Institute (NEI)
First posted: 2016-04-28
Enrollment: 340000
Sex: ALL
Minimum age (years): 1
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: SWIFT I is a series of 3 cluster-randomized trials designed to assess several alternative strategies for trachoma control in communities that have been treated with many years of mass azithromycin distributions. The first trial (named WUHA) compares communities that receive a comprehensive Water, Sanitation, and Hygiene (WASH) package to those that receive no intervention. The second trial (named TAITU-A) compares communities randomized to targeted antibiotic treatment versus those randomized to mass antibiotics for trachoma, and the third trial (TAITU-B) compares communities randomized to targeted antibiotics versus those randomized to delayed antibiotics.

SWIFT II is a continuation of the first trial (WUHA I). WUHA I is an ongoing cluster-randomized trial in rural Ethiopia designed to determine the effectiveness of water, sanitation, and hygiene (WASH) for trachoma. 40 communities were randomized in a 1:1 ratio either to a comprehensive WASH package or to no intervention. The primary outcome is ocular chlamydia, monitored annually for 3 years.

In WUHA II we will treat all 40 WUHA communities with a single mass azithromycin distribution after the month 36 visit, and then continue the WASH intervention only in the 20 communities originally randomized to the WASH arm. We perform annual monitoring visits at months 48, 60, 72, and 84 for the primary outcome of ocular chlamydia among 0-5 year old children. A second aim of WUHA II is to perform a diagnostic test accuracy study of the tests already being conducted as well as several novel tests for trachoma surveillance. The novel tests include inexpensive, point-of-care nucleic acid amplification tests performed on conjunctival swabs, a lateral flow assay for chlamydia seropositivity tested on dried blood spots, and an automated algorithm to detect clinical signs of trachoma from conjunctival photographs. The primary objective of the second aim is to test the sensitivity and specificity of each of these trachoma surveillance tests.

By comparing the combined azithromycin-WASH communities to communities receiving mass azithromycin alone, we investigate the benefit of combining the "A", "F", and "E" components of the SAFE strategy as opposed to focusing on antibiotics alone. This is an important question given the expense of WASH interventions and the limited resources of trachoma programs.

Detailed description: Trachoma is a blinding disease caused by ocular strains of Chlamydia trachomatis. The Carter Center and Proctor Foundation have been jointly conducting trachoma research in the Amhara region of Ethiopia for the past 10 years, through a series of clinical trials. We have found that repeated mass administration of oral azithromycin can greatly reduce the prevalence of trachoma, but mass antibiotics have been unable thus far to eliminate infection.

The World Health Organization recommends not only antibiotics for control of trachoma, but an entire SAFE strategy (Surgery for in-turned eyelids, Antibiotics, Facial hygiene promotion, and Environmental improvements such as latrines and water points). The rationale for the SAFE strategy is based on many years of observational studies on trachoma. Cross-sectional studies have found that clinically active trachoma and ocular chlamydial infection are associated with several indicators of poor hygiene, including dirty faces, face-seeking flies, long distance to water supply, and lack of household latrine. There are few randomized trials testing the impact of WASH improvements on trachoma.

In the past, the WHO has recommended targeted antibiotic treatments to those individuals with active disease, so this could be an alternative treatment strategy that would limit antibiotic use in the community and perhaps be cost-saving. However, little research has assessed targeted treatments as a strategy for trachoma elimination following repeated mass azithromycin distributions.

Our long term goal is to eliminate trachoma even in the most hyperendemic communities. This cluster-randomized clinical trial will determine the role of a comprehensive package of sanitation measures for the elimination of trachoma. We will monitor clinical disease with photography, and monitor infection with a newer chlamydial polymerase chain reaction (PCR) test (Abbott m2000) that is more sensitive than earlier generation tests, and provides quantification. We will monitor other potential health benefits of a WASH intervention and test its overall cost effectiveness. We will also assess a competing strategy for minimizing antibiotic use: that of targeted azithromycin treatments to children testing positive for ocular chlamydia. We will model the long-term cost-effectiveness of these competing strategies for trachoma control after completion of several rounds of mass azithromycin distributions.

Our monitoring has revealed a high uptake of the SWIFT I/WUHA I intervention as well as evidence of subsequent hygiene behavior changes. However, communities started out with a high burden of ocular chlamydia and preliminary data suggests that elimination will be unlikely. We therefore were granted an continuation grant (SWIFT II) to determine the long-term benefit of WASH for trachoma when combined with antibiotics, and second, to explore possibilities for low-cost, highly accurate point-of-care test for chlamydia.

With SWIFT II, we are extending the WUHA I trial by performing a single mass azithromycin distribution in all 40 communities after the final study visit (i.e., month 36), and continuing the WASH intervention in the 20 communities originally randomized to WASH. We are monitoring for ocular chlamydia via PCR of conjunctival swabs. We ask whether antibiotic distributions combined with a comprehensive, well-functioning WASH package is more likely to eliminate trachoma than antibiotics alone. We will also collect extra swabs and dried blood spots during routine monitoring visits and compare several inexpensive, commercially available NAATs and serologic tests for chlamydia. The SWIFT II trial leverages our existing SWIFT I research infrastructure and takes advantage of the fact that the intervention has already been implemented, and will have been operating for more than six years by the end of the proposed study. WASH interventions are thought to take a long time to work given their reliance on changing behavior, and thus we will increase the chances of finding an effect if one truly exists. Moreover, we will advance knowledge regarding trachoma surveillance, which has become increasingly important as the world moves towards global elimination. The results of the SWIFT II study will be of interest to the trachoma community, and regardless of the outcome will directly help trachoma programs decide how to spend their limited resources.

Eligibility criteria: Community Level

* Inclusion Criteria

  * Community in a school district that is within the study area of WagHimra
  * Area within each school district with a site identified for water point construction
  * At least 5 rounds of mass azithromycin distributions had been performed within community
* Exclusion Criteria:

  * School districts that are too difficult to reach (more than a 1-day of travel to access)
  * School districts in the 2 urban regions of the study area, since urban communities have better access to water and sanitation and have less trachoma
  * Refusal of village chief

Individual Level

* Inclusion Criteria:

  * All residents residing within a 1.5km radius from the most promising potential water point the water point sites within the school district that were identified for the study
* Exclusion criteria

  * Refusal of participant \[or parent/guardian\]

Primary outcomes:
measure: Village-specific ocular chlamydia among 0-5 children over time (first trial: WUHA)
timeFrame: 12, 24, 36, 48, 60, 84, 96 months
measure: Ocular chlamydia among 8-12 year olds (second trial: TAITU-A)
timeFrame: 24 months
measure: Incident ocular chlamydia in 0-5 year-olds (third trial: TAITU-B)
timeFrame: 24 months
measure: Trial-based cost-effectiveness of intervention (intervention costs per percent of chlamydia reduction)
timeFrame: 24 months for TAITU, 36 months for WUHA
Secondary outcomes:
measure: Quantitative PCR chlamydia load
timeFrame: 12, 24, 36, 48, 60, 84, 96 months
measure: Follicular trachoma scores; age-stratified (0-5, 6-9, 10 and up for WUHA; 0-5, 8-12 for TAITU)
timeFrame: 12, 24, 36, 48, 60, 84, 96 months
measure: Inflammatory trachoma scores; age-stratified (0-5, 6-9, 10 and up for WUHA; 0-5, 8-12 for TAITU)
timeFrame: 12, 24, 36, 48, 60, 84, 96 months
measure: Clinical trachoma improvement as measured in photography
timeFrame: 12, 24, 36, 48, 60, 84, 96 months
measure: Chlamydial load, individual level analysis
timeFrame: 12, 24, 36, 48, 60, 84, 96 months
measure: Ocular chlamydia; age-stratified (6-9, 10 and up for WUHA; 8-12 for TAITU)
timeFrame: 12, 24, 36, 48, 60, 84, 96 months
measure: Nasopharyngeal pneumococcal macrolide resistance
timeFrame: 12, 24, 36, 96 months
measure: Proportion of the population with clean faces at the village level
timeFrame: 12, 24, 36, 48, 60, 84, 96 months
measure: Childhood growth (height)
timeFrame: 12, 24, 36 months
measure: Childhood growth (weight)
timeFrame: 12, 24, 36 months
measure: Soil-transmitted helminth prevalence
timeFrame: 12, 24, 36 months
measure: Soil-transmitted helminth density
timeFrame: 12, 24, 36 months
measure: Prevalence of chlamydia and other antigen positivity from serological tests
timeFrame: 12, 24, 36, 48, 60, 84, 96 months
measure: Prevalence of stool-based antigen (diarrheal pathogens, soil transmitted helminths) positivity from serological tests
timeFrame: 12, 24, 36, 48, 60, 84, 96 months
measure: Intestinal microbiome from rectal sample
timeFrame: 24 months
measure: Sensitivity and specificity of detecting STH using rectal swabs
timeFrame: 24 months
Other outcomes:
Locations:
city: Addis Ababa
country: Ethiopia
facility: The Carter Center Ethiopia
Study officials:
affiliation: The Carter Center Ethiopia
name: Zerihun Tadese, MD, MPH
role: STUDY_DIRECTOR
affiliation: University of California San Francisco Proctor Foundation
name: Jeremy D Keenan, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: UCSF Proctor Foundation
name: Dionna M Wittberg, MPH
role: STUDY_DIRECTOR
References:
citation: Aragie S, Wittberg DM, Tadesse W, Dagnew A, Hailu D, Chernet A, Melo JS, Aiemjoy K, Haile M, Zeru T, Tadesse Z, Gwyn S, Martin DL, Arnold BF, Freeman MC, Nash SD, Callahan EK, Porco TC, Lietman TM, Keenan JD. Water, sanitation, and hygiene for control of trachoma in Ethiopia (WUHA): a two-arm, parallel-group, cluster-randomised trial. Lancet Glob Health. 2022 Jan;10(1):e87-e95. doi: 10.1016/S2214-109X(21)00409-5.
citation: Wittberg DM, Aragie S, Tadesse W, Melo JS, Aiemjoy K, Chanyalew M, Emerson PM, Freeman MC, Nash SD, Callahan EK, Tadesse Z, Zerihun M, Porco TC, Lietman TM, Keenan JD. WASH Upgrades for Health in Amhara (WUHA): study protocol for a cluster-randomised trial in Ethiopia. BMJ Open. 2021 Feb 22;11(2):e039529. doi: 10.1136/bmjopen-2020-039529.