YawsPhase 3YESA-13NCT01955252
Effect of WHO-yaws Elimination Strategy in Lihir Island, Papua New Guinea
A Phase 3 study testing Azithromycin in people with Yaws, run by Lihir Medical Centre at 1 site in Papua New Guinea.
Trial summary
The trial that the investigators are proposing is a pilot study to determine the effect of the new WHO-yaws eradication strategy in Lihir Island (population 18,000), Papua New Guinea. New treatment policies were developed by WHO in 2012 to replace those of the 1950s. Read more about this study
- Who is it for?
- Ages 2 months and older
- Conditions the study is for
- Yaws
- What is being tested?
- Azithromycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16,000 participants
- Where
- 1 sitePapua New Guinea
- Study dates
- Mar 2013to May 2017
- Phase
- Phase 3
- 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 2 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Whole resident population for MDA and clinical surveys, and children 5-15 years in sentinel sites for cross-sectional serological surveys.
Who cannot join
- Children younger than 2 months and pregnant women;
- Known allergy to macrolide antibiotics;
- Refusal of individual or guardian (for individual inclusion).
Trial locations and contacts
1 site in 1 country.
Papua New Guinea1 site
Lihir Medical Centre
Londolovit, New Ireland Province, 034
About this study
The trial that the investigators are proposing is a pilot study to determine the effect of the new WHO-yaws eradication strategy in Lihir Island (population 18,000), Papua New Guinea. New treatment policies were developed by WHO in 2012 to replace those of the 1950s. The recommended practice is to offer an initial MDA with azithromycin to the entire population, followed by resurveys every 6 months to detect and treat remaining cases.We will use serology surveys, clinical surveys and ulcer aetiology studies to measure the effect of mass azithromycin treatment on the community burden of yaws infection.
Read the detailed description
Yaws is a re-emerging endemic treponemal infection caused by Treponema pallidum subp pertenue. This bacterium causes a chronic relapsing disease, characterized by highly contagious primary and secondary cutaneous lesions and non-contagious tertiary late destructive lesions. The Pacific Islands are believed to be a major focus of yaws worldwide, though population-based data on prevalence are lacking for many countries.
Azithromycin (30mg/kg) has recently been shown to be effective in the treatment of yaws and is now central to WHO's yaws eradication strategy. Substituting a single dose of an oral antibiotic for a painful penicillin injection is a significant advantage because infection control measures required for injection of penicillin will no longer be required and treatment will be more acceptable to communities who need it.
Previous attempts to eradicate yaws by mass treatment of active cases with injectable drugs yielded unsuccessful results. A major campaign to eradicate yaws in the 1950s and 1960s with longacting, injectable penicillin greatly reduced the number of cases of the disease worldwide but incubating and latent cases that were not treated developed relapses with infectious yaws lesions, thereby becoming a source of reinfection.
While the earlier strategy in the 1950s, targeted just those people who were visibly infected, the new WHO-plan calls for blanket coverage of at least 90% of the population. The ratio of clinically apparent to latent cases with no symptoms is estimated as high as 1:6 and mass drug administration (MDA) of the entire population is the best approach to ensure that incubating and latent infections are adequately dealt with.
The currently recommended treatment for eradication is one dose of oral azithromycin (30 mg/Kg; maximum 2g) to be given to entire populations in areas known to harbor yaws. For the MDA to be effective, it is required to have substantial coverage in the first round. The initial mass treatment should be followed by resurveys every 6 months to detect and treat remaining cases.
Because of the potential bacterial resistance appearance treatment failure needs to be monitored. Macrolide resistance is associated with point mutations at positions A2058 and A2059 of the 23S ribosomal RNA gene and molecular analysis need to be done in clinical specimens from patients who do not respond to treatment.
- Conditions
- Yaws
- Being tested
- Azithromycin
- Keywords
- Endemic treponematoses, Azithromycin, Mass drug administration, Eradication
- Medical subject headings
- Yaws
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzithromycinDrug
Also called Azithromycin tablets 500mg (Medopharm), Zithromax
Investigators will do a baseline survey of every children from 5 to 15 years in the village. To detect yaws infection, investigators will collect a blood specimen for serology (qualitative and quantitative RPR testing and TPHA assay).
Investigators will identify yaws-like ulcers by means of dermatological examination. Investigators will swab papilloma and ulcers and specimens will be flown to University of Washington (Seattle). PCR methods will consist of primary screening for the presence or absence of T. p. pertenue DNA, Haemophilus ducreyi DNA and detection of the A2058G and A2059G mutations associated with azithromycin resistance.
Investigators will begin treatment with antibiotics immediately after completion of the baseline survey. Everyone in the villages will be offered azithromycin, subsequently a field team will treat all active clinical cases and their contacts 6 monthly.
For all subjects, follow-up examination will be performed at 6,12,18,24,30,36,40,and 42 months
| Study group | Role | What they receive |
|---|---|---|
| Azithromycin | Experimental | All participants older than 2 months (population 18,000) will be offered a single oral dose of oral azithromycin (tablets) 30 mg per Kg up to a maximum dose of 2g.
Women who tell the investigators they are pregnant and people with known allergy to macrolides will be offered benzathine benzylpenicillin.
This will be a single arm study. Study participants who met the inclusion criteria and agree to sign the consent form will be managed with proposed drug and systematically observed to measure outcomes of interest. Receives: Drug: Azithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of yaws latent infection
Prevalence of yaws infection is determined by the combination of a positive TPHA and RPR titer of 1:4 or above (which can be considered as the marker for true disease) in 1200 children 5-15 years in 6 randomly selected villages.
Measured: 42 months
Secondary outcomes (3)
Prevalence of active yaws disease
Determined by means of dermatological examination (WHO definitions) with laboratory confirmation using serology and PCR methods.
Measured: 42 months
Macrolide resistance
Estimate the prevalence of molecular markers of macrolide resistance in T. pallidum subsp. pertenue in patients with active yaws both before and after the mass drug administration.
Measured: 42 months
Ulcer aetiology surveys
PCR-surveillance of yaws-like ulcers in randomly selected villages every survey. This will allow to compare the relative proportion of T. pallidum pertenue ulcers vs other aetiological agents
Measured: 42 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2013 (estimated)
- Study startMar 2013
- Primary completionMay 2017
- Study completionMay 2017
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 YawsStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lihir Medical Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Barcelona Institute for Global Health, National Department of Health, Papua New Guinea, World Health Organization, University of Washington
- Responsible party
- Principal investigator, Oriol Mitja, Lihir Medical Centre
- Investigators
- Oriol Mitja, MD, PhD, Principal investigator, Barcelona Institute for Global Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01955252
- Sponsor's protocol ID
- YESA-13
- Acronym
- YESA-13
- Status last verified
- Jan 2017
- First submitted
- 24 Sep 2013
- Last updated
- 28 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Mitja O, Godornes C, Houinei W, Kapa A, Paru R, Abel H, Gonzalez-Beiras C, Bieb SV, Wangi J, Barry AE, Sanz S, Bassat Q, Lukehart SA. Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study. Lancet. 2018 Apr 21;391(10130):1599-1607. doi: 10.1016/S0140-6736(18)30204-6. Epub 2018 Feb 7.
PubMed 29428183Mitja O, Gonzalez-Beiras C, Godornes C, Kolmau R, Houinei W, Abel H, Kapa A, Paru R, Bieb SV, Wangi J, Sanz S, Asiedu K, Lukehart SA, Bassat Q. Effectiveness of single-dose azithromycin to treat latent yaws: a longitudinal comparative cohort study. Lancet Glob Health. 2017 Dec;5(12):e1268-e1274. doi: 10.1016/S2214-109X(17)30388-1. Epub 2017 Oct 26.
PubMed 29107621Mitja O, Houinei W, Moses P, Kapa A, Paru R, Hays R, Lukehart S, Godornes C, Bieb SV, Grice T, Siba P, Mabey D, Sanz S, Alonso PL, Asiedu K, Bassat Q. Mass treatment with single-dose azithromycin for yaws. N Engl J Med. 2015 Feb 19;372(8):703-10. doi: 10.1056/NEJMoa1408586.
PubMed 25693010
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of WHO-yaws Elimination Strategy in Lihir Island, Papua New Guinea
- ClinicalTrials.gov ID
- NCT01955252
- Acronym / sponsor ID
- YESA-13 / YESA-13
- Conditions
- Yaws
- Keywords
- Endemic treponematoses, Azithromycin, Mass drug administration, Eradication
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16,000 participants (actual)
- Lead sponsor
- Lihir Medical CentreUniversity, hospital or other
- Collaborators
- Barcelona Institute for Global Health, National Department of Health, Papua New Guinea, World Health Organization, University of Washington
- Study start
- Mar 2013
- Primary completion
- May 2017 (actual)
- Study completion
- May 2017 (actual)
- First posted
- 7 Oct 2013 (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.
The trial that the investigators are proposing is a pilot study to determine the effect of the new WHO-yaws eradication strategy in Lihir Island (population 18,000), Papua New Guinea. New treatment policies were developed by WHO in 2012 to replace those of the 1950s. The recommended practice is to offer an initial MDA with azithromycin to the entire population, followed by resurveys every 6 months to detect and treat remaining cases.We will use serology surveys, clinical surveys and ulcer aetiology studies to measure the effect of mass azithromycin treatment on the community burden of yaws infection.
Detailed description
Yaws is a re-emerging endemic treponemal infection caused by Treponema pallidum subp pertenue. This bacterium causes a chronic relapsing disease, characterized by highly contagious primary and secondary cutaneous lesions and non-contagious tertiary late destructive lesions. The Pacific Islands are believed to be a major focus of yaws worldwide, though population-based data on prevalence are lacking for many countries.
Azithromycin (30mg/kg) has recently been shown to be effective in the treatment of yaws and is now central to WHO's yaws eradication strategy. Substituting a single dose of an oral antibiotic for a painful penicillin injection is a significant advantage because infection control measures required for injection of penicillin will no longer be required and treatment will be more acceptable to communities who need it.
Previous attempts to eradicate yaws by mass treatment of active cases with injectable drugs yielded unsuccessful results. A major campaign to eradicate yaws in the 1950s and 1960s with longacting, injectable penicillin greatly reduced the number of cases of the disease worldwide but incubating and latent cases that were not treated developed relapses with infectious yaws lesions, thereby becoming a source of reinfection.
While the earlier strategy in the 1950s, targeted just those people who were visibly infected, the new WHO-plan calls for blanket coverage of at least 90% of the population. The ratio of clinically apparent to latent cases with no symptoms is estimated as high as 1:6 and mass drug administration (MDA) of the entire population is the best approach to ensure that incubating and latent infections are adequately dealt with.
The currently recommended treatment for eradication is one dose of oral azithromycin (30 mg/Kg; maximum 2g) to be given to entire populations in areas known to harbor yaws. For the MDA to be effective, it is required to have substantial coverage in the first round. The initial mass treatment should be followed by resurveys every 6 months to detect and treat remaining cases.
Because of the potential bacterial resistance appearance treatment failure needs to be monitored. Macrolide resistance is associated with point mutations at positions A2058 and A2059 of the 23S ribosomal RNA gene and molecular analysis need to be done in clinical specimens from patients who do not respond to treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Azithromycin | Experimental | Drug: AzithromycinAll participants older than 2 months (population 18,000) will be offered a single oral dose of oral azithromycin (tablets) 30 mg per Kg up to a maximum dose of 2g. Women who tell the investigators they are pregnant and people with known allergy to macrolides will be offered benzathine benzylpenicillin. This will be a single arm study. Study participants who met the inclusion criteria and agree to sign the consent form will be managed with proposed drug and systematically observed to measure outcomes of interest. |
Who may qualify
- Ages
- 2 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Whole resident population for MDA and clinical surveys, and children 5-15 years in sentinel sites for cross-sectional serological surveys.
Key exclusion criteria (3 listed)
- Children younger than 2 months and pregnant women;
- Known allergy to macrolide antibiotics;
- Refusal of individual or guardian (for individual inclusion).
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 |
|---|---|---|
| AzithromycinAlso: Azithromycin tablets 500mg (Medopharm), ZithromaxInvestigators will do a baseline survey of every children from 5 to 15 years in the village. To detect yaws infection, investigators will collect a blood specimen for serology (qualitative and quantitative RPR testing and TPHA assay). Investigators will identify yaws-like ulcers by means of dermatological examination. Investigators will swab papilloma and ulcers and specimens will be flown to University of Washington (Seattle). PCR methods will consist of primary screening for the presence or absence of T. p. pertenue DNA, Haemophilus ducreyi DNA and detection of the A2058G and A2059G mutations associated with azithromycin resistance. Investigators will begin treatment with antibiotics immediately after completion of the baseline survey. Everyone in the villages will be offered azithromycin, subsequently a field team will treat all active clinical cases and their contacts 6 monthly. For all subjects, follow-up examination will be performed at 6,12,18,24,30,36,40,and 42 months | Drug | Azithromycin |
Primary outcome
Prevalence of yaws latent infection
Time frame: 42 months
Prevalence of yaws infection is determined by the combination of a positive TPHA and RPR titer of 1:4 or above (which can be considered as the marker for true disease) in 1200 children 5-15 years in 6 randomly selected villages.
3 secondary outcomes
Prevalence of active yaws disease
Time frame: 42 months
Macrolide resistance
Time frame: 42 months
Ulcer aetiology surveys
Time frame: 42 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 28 Aug 2017.
- Derived from this study: PubMed 29428183Mitja O, Godornes C, Houinei W, Kapa A, Paru R, Abel H, Gonzalez-Beiras C, Bieb SV, Wangi J, Barry AE, Sanz S, Bassat Q, Lukehart SA. Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study. Lancet. 2018 Apr 21;391(10130):1599-1607. doi: 10.1016/S0140-6736(18)30204-6. Epub 2018 Feb 7.
- Derived from this study: PubMed 29107621Mitja O, Gonzalez-Beiras C, Godornes C, Kolmau R, Houinei W, Abel H, Kapa A, Paru R, Bieb SV, Wangi J, Sanz S, Asiedu K, Lukehart SA, Bassat Q. Effectiveness of single-dose azithromycin to treat latent yaws: a longitudinal comparative cohort study. Lancet Glob Health. 2017 Dec;5(12):e1268-e1274. doi: 10.1016/S2214-109X(17)30388-1. Epub 2017 Oct 26.
- Derived from this study: PubMed 25693010Mitja O, Houinei W, Moses P, Kapa A, Paru R, Hays R, Lukehart S, Godornes C, Bieb SV, Grice T, Siba P, Mabey D, Sanz S, Alonso PL, Asiedu K, Bassat Q. Mass treatment with single-dose azithromycin for yaws. N Engl J Med. 2015 Feb 19;372(8):703-10. doi: 10.1056/NEJMoa1408586.
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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.
Oriol Mitja, MD, PhD principal investigator
Barcelona Institute for Global Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Azithromycin in people with Yaws, run by Lihir Medical Centre at 1 site in Papua New Guinea.
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 3 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 28 Aug 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 Papua New Guinea. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Prevalence of yaws latent infection (time frame: 42 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 NCT01955252, 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 28 Aug 2017.