TrachomaPhase 4TIRETNCT01202331
Tripartite International Research for the Elimination of Trachoma
A Phase 4 study testing mass treatment with oral azithromycin in people with Trachoma and Chlamydia, run by University of California, San Francisco at 1 site in Ethiopia.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 day and olderHealthy volunteers can take part
- What is being tested?
- mass treatment with oral azithromycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29,000 participants
- Where
- 1 siteEthiopia
- Study dates
- Nov 2010to May 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- All residents residing in the state-teams which are randomly selected for this study.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
- We hypothesize that Chlamydial infection will return to communities when treatment ends.
- We hypothesize that infection will be completely eliminated in all communities treated for seven years.
- 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.
Read the 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.
- Being tested
- mass treatment with oral azithromycin
- Keywords
- Bacterial Infections, Chlamydia Infections, Eye Diseases
- Medical subject headings
- Trachoma, Chlamydia Infections, Bacterial Infections, Eye Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mass treatment with oral azithromycinDrug
Also called Zithromax
For baseline and follow-up surveys prior to azithromycin distribution, a stratified random sample from two age groups will be chosen: 1) 60 study participants younger than 10 years old and 2) 60 study participants aged 10 years and above. Clinical examination will be performed and conjunctival swabs will be taken from all the study participants. Nasopharyngeal swabs will be collected in each community from 15 randomly selected children among the 60 participants under age 10 who were recruited for conjunctival swabbing. Then a single dose of azithromycin will be distributed according to study design: in tablet form for adults; a weight-adjusted tablet dose for children ages 8-10; and pediatric suspension for children ages 1 - 7.
| Study group | Role | What they receive |
|---|---|---|
| J | No intervention | Stop Annual Treatment |
| K | No intervention | Stop Biannual Treatment |
| L | Other | Continue Annual Treatment Receives: Drug: mass treatment with oral azithromycin |
| M | Other | Continue Biannual Treatment Receives: Drug: mass treatment with oral azithromycin |
| N | Experimental | Targeted Treatment by Age Receives: Drug: mass treatment with oral azithromycin |
| O | Experimental | Targeted Treatment by Clinical Exam Receives: Drug: mass treatment with oral azithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 36 months
Secondary outcomes (9)
Clinical active trachoma in community, as determined by the WHO simplified grading system
Measured: 36 months
Childhood mortality (6 months -5 years of age), 6-10 years of age, and >10 years
Measured: 36 months
Macrolide resistance in pneumococcus, Haemophilus influenzae, and Staphylococcus aureus (% resistance over time, clustered by randomization unit)
Measured: 36 months
Anthropometric measurements (weight and height), as outlined by WHO child growth standards (0-5 years of age)
Measured: 3, 12, 24, and 36 months after baseline
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
Measured: 36 months
Prevalence of anemia (hemoglobin levels in 0-9 year olds) and the prevalence of malaria
Measured: 36 months
Clinically active trachoma in a school (all children under age 10), as determined by the WHO simplified grading system
Measured: 36 months
Cost-effectiveness of mass azithromycin administration, per infection year prevented and cost per eliminated village
Measured: 0, 12, 24, and 36 months
Estimate of chlamydial load from real-time, qPCR
Measured: 0, 12, 24, 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2010 (estimated)
- Study startNov 2010
- Primary completionNov 2013
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for TrachomaStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 29,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Thomas M. Lietman, University of California, San Francisco
- Investigators
- Tom Lietman, MD, Principal investigator, F.I. Proctor Foundation, UCSFKieran S O'Brien, MPH, Study director, F.I. Proctor Foundation, UCSFPaul Emerson, PhD, Study director, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01202331
- Sponsor's protocol ID
- 10-02169
- Acronym
- TIRET
- Status last verified
- Oct 2017
- First submitted
- 13 Sep 2010
- Last updated
- 11 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Mahmud H, Haile BA, Tadesse Z, Gebresillasie S, Shiferaw A, Zerihun M, Liu Z, Callahan EK, Cotter SY, Varnado NE, Oldenburg CE, Porco TC, Lietman TM, Keenan JD. Targeted Mass Azithromycin Distribution for Trachoma: A Community-Randomized Trial (TANA II). Clin Infect Dis. 2023 Aug 14;77(3):388-395. doi: 10.1093/cid/ciad211.
PubMed 37021692Keenan 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.
PubMed 31166952Keenan 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.
PubMed 30106956
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tripartite International Research for the Elimination of Trachoma
- ClinicalTrials.gov ID
- NCT01202331
- Acronym / sponsor ID
- TIRET / 10-02169
- Keywords
- Bacterial Infections, Chlamydia Infections, Eye Diseases
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29,000 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- Nov 2010
- Primary completion
- Nov 2013 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 15 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- We hypothesize that Chlamydial infection will return to communities when treatment ends.
- We hypothesize that infection will be completely eliminated in all communities treated for seven years.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| J | No intervention | –Stop Annual Treatment |
| K | No intervention | –Stop Biannual Treatment |
| L | Other | Drug: mass treatment with oral azithromycinContinue Annual Treatment |
| M | Other | Drug: mass treatment with oral azithromycinContinue Biannual Treatment |
| N | Experimental | Drug: mass treatment with oral azithromycinTargeted Treatment by Age |
| O | Experimental | Drug: mass treatment with oral azithromycinTargeted Treatment by Clinical Exam |
Who may qualify
- Ages
- 1 day and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- All residents residing in the state-teams which are randomly selected for this study.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| mass treatment with oral azithromycinAlso: ZithromaxFor baseline and follow-up surveys prior to azithromycin distribution, a stratified random sample from two age groups will be chosen: 1) 60 study participants younger than 10 years old and 2) 60 study participants aged 10 years and above. Clinical examination will be performed and conjunctival swabs will be taken from all the study participants. Nasopharyngeal swabs will be collected in each community from 15 randomly selected children among the 60 participants under age 10 who were recruited for conjunctival swabbing. Then a single dose of azithromycin will be distributed according to study design: in tablet form for adults; a weight-adjusted tablet dose for children ages 8-10; and pediatric suspension for children ages 1 - 7. | Drug | L, M, N, O |
Primary outcome
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)
Time frame: 36 months
9 secondary outcomes
Clinical active trachoma in community, as determined by the WHO simplified grading system
Time frame: 36 months
Childhood mortality (6 months -5 years of age), 6-10 years of age, and >10 years
Time frame: 36 months
Macrolide resistance in pneumococcus, Haemophilus influenzae, and Staphylococcus aureus (% resistance over time, clustered by randomization unit)
Time frame: 36 months
Anthropometric measurements (weight and height), as outlined by WHO child growth standards (0-5 years of age)
Time frame: 3, 12, 24, and 36 months after baseline
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
Time frame: 36 months
Prevalence of anemia (hemoglobin levels in 0-9 year olds) and the prevalence of malaria
Time frame: 36 months
Clinically active trachoma in a school (all children under age 10), as determined by the WHO simplified grading system
Time frame: 36 months
Cost-effectiveness of mass azithromycin administration, per infection year prevented and cost per eliminated village
Time frame: 0, 12, 24, and 36 months
Estimate of chlamydial load from real-time, qPCR
Time frame: 0, 12, 24, 36 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2017.
- Derived from this study: PubMed 37021692Mahmud H, Haile BA, Tadesse Z, Gebresillasie S, Shiferaw A, Zerihun M, Liu Z, Callahan EK, Cotter SY, Varnado NE, Oldenburg CE, Porco TC, Lietman TM, Keenan JD. Targeted Mass Azithromycin Distribution for Trachoma: A Community-Randomized Trial (TANA II). Clin Infect Dis. 2023 Aug 14;77(3):388-395. doi: 10.1093/cid/ciad211.
- Derived from this study: PubMed 31166952Keenan 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.
- Derived from this study: PubMed 30106956Keenan 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tom Lietman, MD principal investigator
F.I. Proctor Foundation, UCSF
Kieran S O'Brien, MPH study director
F.I. Proctor Foundation, UCSF
Paul Emerson, PhD study director
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing mass treatment with oral azithromycin in people with Trachoma and Chlamydia, run by University of California, San Francisco at 1 site in Ethiopia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Ethiopia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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) (time frame: 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01202331, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Oct 2017.