YawsPhase 3NCT01382004
Single-dose Azithromycin for the Treatment of Yaws
A Phase 3 study testing Penicillin-G-benzathine and Azithromycin in people with Yaws and Treponema Infection, run by Lihir Medical Centre at 1 site in Papua New Guinea.
Trial summary
Yaws, an endemic treponematosis and as such a neglected tropical disease (NTD), is currently making a comeback in children in rural areas. Injectable long acting penicillin remains the drug of choice for the treatment of yaws. Read more about this study
- Who is it for?
- Ages 6 months to 15 years
- Conditions the study is for
- Yaws, Treponema Infection, Neglected Tropical Disease
- What is being tested?
- Penicillin-G-benzathine and Azithromycin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 255 participants
- Where
- 1 sitePapua New Guinea
- Study dates
- Sep 2010to Sep 2011
- 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 6 months to 15 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- All children 6 months to 15 years of age who present to LMC with suggestive skin lesions or joint pains and VDRL and TPHA testing are positive
- Suggestive skin lesions defined as: Symptomatic > 4 weeks, painless, a traumatic ulcers with raised margins. VDRL positive when titer of at least 1:16
Who cannot join
- Pregnancy
- Less than 6 months of age
- Known allergy to penicillin or macrolide
- Use of antibiotics active against treponema during the preceding six months (penicillin-G-benzathine, ceftriaxone, azithromycin or doxycycline)
Trial locations and contacts
1 site in 1 country.
Papua New Guinea1 site
Lihir Medical Centre
Kavieng, New Ireland Province, 034
About this study
Official title: Single-dose Azithromycin Versus Penicillin G Benzathine for the Treatment of Yaws in Children
Yaws, an endemic treponematosis and as such a neglected tropical disease (NTD), is currently making a comeback in children in rural areas. Injectable long acting penicillin remains the drug of choice for the treatment of yaws. However, on the basis of successful experience with venereal syphilis in large-scale studies, oral azithromycin has emerged as a potential alternative that overcomes the major medical and logistic disadvantages of the current regimen.
In this non-inferiority randomized clinical trial the investigators propose a comparable scheme for the treatment of yaws, to test the efficacy of a single, oral dose of azithromycin versus a single, i.m. dose of benzathine penicillin G.Sample size has been calculated to detect a non-inferiority margin of 10%. Children < 15 years of age with a confirmed diagnosis of yaws will be randomly assigned to receive 30mg/Kg (maximum 2g) of azithromycin orally or 50.000units/Kg (maximum 2.4MU) of penicillin-G-benzathine intramuscularly. The primary outcome is treatment efficacy, with cure defined serologically (a decline in the VDRL titer of at least two dilutions by six months after treatment) and, in primary yaws, also by epithelialization of ulcers within two weeks.
Read the detailed description
Regulatory status: Investigational - Randomized Clinical Trial. Registered product for antibacterial therapy
BACKGROUND Penicillin remains the drug of choice for the treatment of endemic treponematoses including yaws. This type of treatment is effective and cheap. There are, however, some disadvantages: the pain associated with a large volume (4 ml) deep i.m. injection, a high prevalence of self-reported allergy to penicillin, structural and logistic problems related to a treatment based on injection of drugs.
Azithromycin, a macrolide antibiotic with a long (68 hours) half-life in tissue and proven efficacy against T.pallidum is a promising candidate. In two randomized trials, for the treatment of syphilis in adults, a single 2-g oral dose of azithromycin achieved cure rates equivalent to that of standard treatment with 2.4 MU of penicillin G benzathine. On the basis of experience with venereal syphilis, azithromycin has emerged as an alternative treatment for Yaws. It represents a more accessible treatment as it could be prescribed by village health workers and therefore enable yaws control to be more easily incorporated into other primary health-care programmes.
The product is available as an oral tablet to be administered at a single dose of 30mg/Kg in children and 2 g in adults. Safety and efficacy using azithromycin 30 mg/kg given as a single dose in the treatment of pediatric patients over 6 months of age with otitis media have been established and approved by the FDA.
INFORMED CONSENT All participants (or their guardian or parents) who are eligible for enrolment in the trial according to biological and demographic inclusion criteria are provided with detailed information on the purpose of the trial and on risks and benefits of participation, according to information listed in an information sheet. Consent is provided in writing.
SAMPLE SIZE JUSTIFICATION
The sample size would be 244; It was calculated on the basis of a non-inferiority trial design and the following assumptions:
Statistical power of 80 percent;to exclude the possibility that the absolute efficacy of azithromycin was at least 10% percent less than that of penicillin; 5% significance level using a one-sided equivalence test of proportions; assuming that the true efficacy of each agent was equivalent at 95 percent and that approximately 10 percent of participants would be lost to follow-up.
RANDOMIZATION PROCEDURE A random allocation schedule, stratified according to study group, will be generated centrally with the use of blocked randomization, random permuted blocks of four, and a 1:1 allocation ratio. The allocation will be concealed from investigators through the use of sequentially numbered, sealed envelopes
- Conditions
- Yaws, Treponema Infection, Neglected Tropical Disease
- Being tested
- Penicillin-G-benzathine, Azithromycin
- Keywords
- Neglected diseases, Children
- Medical subject headings
- Yaws, Treponemal Infections, Neglected Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Penicillin-G-benzathineDrug
Also called Zithromax, Bicillin LA
Screening examination: Medical history (emphasis on skin lesions and bone signs) Physical examination.Blood samples for VDRL and TPHA. Clinical safety. Laboratory evaluations: haemoglobin, total WBC count, differential WBC count, platelet count, ALT, AST, urea and creatinine.
Routine assessments: General clinical assessment and physical examination on Days 0 (treatment administered) and 14. Adverse events and concomitant medications (at baseline, Day 14 and in any unscheduled visit). Photograph documentation of skin lesions (at 14 days follow up visit). Follow-up visits performed on 3 and 6 will have a ± 14 days allowable window
AzithromycinDrug
Screening examination: Medical history (emphasis on skin lesions and bone signs) Physical examination.Blood samples for VDRL and TPHA. Clinical safety. Laboratory evaluations: haemoglobin, total WBC count, differential WBC count, platelet count, ALT, AST, urea and creatinine.
Routine assessments: General clinical assessment and physical examination on Days 0 (treatment administered) and 14. Adverse events and concomitant medications (at baseline, Day 14 and in any unscheduled visit). Photograph documentation of skin lesions (at 14 days follow up visit). Follow-up visits performed on 3 and 6 will have a ± 14 days allowable window
| Study group | Role | What they receive |
|---|---|---|
| Penicillin-G-Benzathine | Active comparator | penicillin-G-Benzathine : 50,000 UI/Kg single dose(maximum 2.4 million units IM) Receives: Drug: Penicillin-G-benzathine |
| Azithromycin | Experimental | Azithromycin: 30 mg/kg single dose (Maximum: 2.000 mg.) Receives: Drug: Azithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serologic cure
Serologic cure, defined as a decrease in the VDRL titer by at least two dilutions at six month follow-up examination, with the titer at the time of treatment used as the baseline.
In the case of primary skin lesions, complete resolution or improvement of lesions within two weeks after treatment is also required.
Measured: 6 months follow up
Secondary outcomes (2)
clinical cure
Clinical cure (improvement 14 days after treatment, assessed by photograph comparison over the time)
Measured: 6 months
3 months cure rate
Serological Cure rates three months after treatment
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2011 (estimated)
- Study startSep 2010
- Primary completionSep 2011
- Study completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 255 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lihir Medical Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Centre For International Health
- Responsible party
- Principal investigator, Oriol Mitja, Lihir Medical Centre
- Investigators
- Quique Bassat, MD, PhD, Study director, Centre for International Health Research/Hospital Clínic/University of barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01382004
- Sponsor's protocol ID
- YAWS-AZ01
- Status last verified
- Apr 2012
- First submitted
- 23 Jun 2011
- Last updated
- 13 Apr 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Mitja O, Hays R, Ipai A, Penias M, Paru R, Fagaho D, de Lazzari E, Bassat Q. Single-dose azithromycin versus benzathine benzylpenicillin for treatment of yaws in children in Papua New Guinea: an open-label, non-inferiority, randomised trial. Lancet. 2012 Jan 28;379(9813):342-7. doi: 10.1016/S0140-6736(11)61624-3. Epub 2012 Jan 11.
PubMed 22240407
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-dose Azithromycin Versus Penicillin G Benzathine for the Treatment of Yaws in Children
- ClinicalTrials.gov ID
- NCT01382004
- Acronym / sponsor ID
- YAWS-AZ01
- Conditions
- Yaws, Treponema Infection, Neglected Tropical Disease
- Keywords
- Neglected diseases, Children
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 255 participants (actual)
- Lead sponsor
- Lihir Medical CentreUniversity, hospital or other
- Collaborators
- Centre For International Health
- Study start
- Sep 2010
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 27 Jun 2011 (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.
Yaws, an endemic treponematosis and as such a neglected tropical disease (NTD), is currently making a comeback in children in rural areas. Injectable long acting penicillin remains the drug of choice for the treatment of yaws. However, on the basis of successful experience with venereal syphilis in large-scale studies, oral azithromycin has emerged as a potential alternative that overcomes the major medical and logistic disadvantages of the current regimen.
In this non-inferiority randomized clinical trial the investigators propose a comparable scheme for the treatment of yaws, to test the efficacy of a single, oral dose of azithromycin versus a single, i.m. dose of benzathine penicillin G.Sample size has been calculated to detect a non-inferiority margin of 10%. Children < 15 years of age with a confirmed diagnosis of yaws will be randomly assigned to receive 30mg/Kg (maximum 2g) of azithromycin orally or 50.000units/Kg (maximum 2.4MU) of penicillin-G-benzathine intramuscularly. The primary outcome is treatment efficacy, with cure defined serologically (a decline in the VDRL titer of at least two dilutions by six months after treatment) and, in primary yaws, also by epithelialization of ulcers within two weeks.
Detailed description
Regulatory status: Investigational - Randomized Clinical Trial. Registered product for antibacterial therapy
BACKGROUND Penicillin remains the drug of choice for the treatment of endemic treponematoses including yaws. This type of treatment is effective and cheap. There are, however, some disadvantages: the pain associated with a large volume (4 ml) deep i.m. injection, a high prevalence of self-reported allergy to penicillin, structural and logistic problems related to a treatment based on injection of drugs.
Azithromycin, a macrolide antibiotic with a long (68 hours) half-life in tissue and proven efficacy against T.pallidum is a promising candidate. In two randomized trials, for the treatment of syphilis in adults, a single 2-g oral dose of azithromycin achieved cure rates equivalent to that of standard treatment with 2.4 MU of penicillin G benzathine. On the basis of experience with venereal syphilis, azithromycin has emerged as an alternative treatment for Yaws. It represents a more accessible treatment as it could be prescribed by village health workers and therefore enable yaws control to be more easily incorporated into other primary health-care programmes.
The product is available as an oral tablet to be administered at a single dose of 30mg/Kg in children and 2 g in adults. Safety and efficacy using azithromycin 30 mg/kg given as a single dose in the treatment of pediatric patients over 6 months of age with otitis media have been established and approved by the FDA.
INFORMED CONSENT All participants (or their guardian or parents) who are eligible for enrolment in the trial according to biological and demographic inclusion criteria are provided with detailed information on the purpose of the trial and on risks and benefits of participation, according to information listed in an information sheet. Consent is provided in writing.
SAMPLE SIZE JUSTIFICATION
The sample size would be 244; It was calculated on the basis of a non-inferiority trial design and the following assumptions:
Statistical power of 80 percent;to exclude the possibility that the absolute efficacy of azithromycin was at least 10% percent less than that of penicillin; 5% significance level using a one-sided equivalence test of proportions; assuming that the true efficacy of each agent was equivalent at 95 percent and that approximately 10 percent of participants would be lost to follow-up.
RANDOMIZATION PROCEDURE A random allocation schedule, stratified according to study group, will be generated centrally with the use of blocked randomization, random permuted blocks of four, and a 1:1 allocation ratio. The allocation will be concealed from investigators through the use of sequentially numbered, sealed envelopes
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Penicillin-G-Benzathine | Active comparator | Drug: Penicillin-G-benzathinepenicillin-G-Benzathine : 50,000 UI/Kg single dose(maximum 2.4 million units IM) |
| Azithromycin | Experimental | Drug: AzithromycinAzithromycin: 30 mg/kg single dose (Maximum: 2.000 mg.) |
Who may qualify
- Ages
- 6 months to 15 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- All children 6 months to 15 years of age who present to LMC with suggestive skin lesions or joint pains and VDRL and TPHA testing are positive
- Suggestive skin lesions defined as: Symptomatic > 4 weeks, painless, a traumatic ulcers with raised margins. VDRL positive when titer of at least 1:16
Key exclusion criteria (4 listed)
- Pregnancy
- Less than 6 months of age
- Known allergy to penicillin or macrolide
- Use of antibiotics active against treponema during the preceding six months (penicillin-G-benzathine, ceftriaxone, azithromycin or doxycycline)
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 |
|---|---|---|
| Penicillin-G-benzathineAlso: Zithromax, Bicillin LAScreening examination: Medical history (emphasis on skin lesions and bone signs) Physical examination.Blood samples for VDRL and TPHA. Clinical safety. Laboratory evaluations: haemoglobin, total WBC count, differential WBC count, platelet count, ALT, AST, urea and creatinine. Routine assessments: General clinical assessment and physical examination on Days 0 (treatment administered) and 14. Adverse events and concomitant medications (at baseline, Day 14 and in any unscheduled visit). Photograph documentation of skin lesions (at 14 days follow up visit). Follow-up visits performed on 3 and 6 will have a ± 14 days allowable window | Drug | Penicillin-G-Benzathine |
| AzithromycinScreening examination: Medical history (emphasis on skin lesions and bone signs) Physical examination.Blood samples for VDRL and TPHA. Clinical safety. Laboratory evaluations: haemoglobin, total WBC count, differential WBC count, platelet count, ALT, AST, urea and creatinine. Routine assessments: General clinical assessment and physical examination on Days 0 (treatment administered) and 14. Adverse events and concomitant medications (at baseline, Day 14 and in any unscheduled visit). Photograph documentation of skin lesions (at 14 days follow up visit). Follow-up visits performed on 3 and 6 will have a ± 14 days allowable window | Drug | Azithromycin |
Primary outcome
Serologic cure
Time frame: 6 months follow up
Serologic cure, defined as a decrease in the VDRL titer by at least two dilutions at six month follow-up examination, with the titer at the time of treatment used as the baseline. In the case of primary skin lesions, complete resolution or improvement of lesions within two weeks after treatment is also required.
2 secondary outcomes
clinical cure
Time frame: 6 months
3 months cure rate
Time frame: 3 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 13 Apr 2012.
- Derived from this study: PubMed 22240407Mitja O, Hays R, Ipai A, Penias M, Paru R, Fagaho D, de Lazzari E, Bassat Q. Single-dose azithromycin versus benzathine benzylpenicillin for treatment of yaws in children in Papua New Guinea: an open-label, non-inferiority, randomised trial. Lancet. 2012 Jan 28;379(9813):342-7. doi: 10.1016/S0140-6736(11)61624-3. Epub 2012 Jan 11.
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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.
Quique Bassat, MD, PhD study director
Centre for International Health Research/Hospital Clínic/University of barcelona
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 Penicillin-G-benzathine and Azithromycin in people with Yaws and Treponema Infection, 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 2 inclusion and 4 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 13 Apr 2012. 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?
Serologic cure (time frame: 6 months follow up). 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 NCT01382004, which also lists 1 linked publication.
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 13 Apr 2012.