Yaws
Conditions
Brief summary
The study will be a single blinded, randomized, controlled open label non-inferiority phase III, trial with two parallel groups, conducted in Ghana and Papua New Guinea (PNG). The ultimate goal is to establish if a 20mg/kg dose of azithromycin is as effective as a 30mg/kg dose in the treatment of yaws. Approximately 600 clinically and serologically diagnosed yaws patients will be included in the study. Patients will be randomized to receive treatment with the two antibiotic regimens as follow: (i) Regimen I (AZT20): Single oral dose of 20 mg/kg azithromycin (ii) Regimen II (AZT30): Single oral dose of 30 mg/kg azithromycin. The follow-up period of patients will be 6 months. Assessments before, during and after the antibiotic treatment will include full medical history, clinical assessment of the lesion and, laboratory investigations. The primary efficacy parameters are healing of the lesion at 4 weeks and a four-fold decline in RPR titre at 6 months after start of treatment.
Interventions
DRUGAzithromycin
Comparison of two different dosing strategies for the treatment of yaws
Sponsors
World Health Organization
Centers for Disease Control and Prevention
Kwame Nkrumah University of Science and Technology
Barcelona Institute for Global Health
Papua New Guinea Institute of Medical Research
Ghana Health Services
Noguchi Memorial Institute for Medical Research
Papua New Guinea National Department of Health
University of Health and Allied Sciences
London School of Hygiene and Tropical Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
6 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* Aged 6 to 16 years * Clinical lesion consistent with primary or secondary yaws -Primary ulcer or papilloma * Dually-Positive Chembio DPP Syphilis Screen & Confirm * Informed Consent and Assent (for children 12-16 years)
Exclusion criteria
1. Known allergy to azithromycin or macrolides. 2. Treatment with long-acting penicillin or alternative antibiotic with activity against T. pallidum within the last 3 months (ceftriaxone, azithromycin or doxycycline, amoxicillin). 3. Patients with current treatment with any drugs likely to interact with the study medication. 4. Patients who are unable to take oral medication or having gastrointestinal disease likely to interfere with drug absorption. 5. Patients who may not be able to comply with the requirements of the study protocol including follow up visits. 6. Patients who are not willing to give informed consent (patient and/or parent/legal representative), or who withdraw consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical and Serological Cure | 6 Months | Clinical resolution of skin lesion at 4 weeks and at least four-fold decline in Rapid Plasma Reagin titre or seroreversion at 6-month (compared to baseline) in T.pallidum subsp. pertenue Polymerase Chain Reaction-confirmed subjects with yaws. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical and Serological Cure in Latent Yaws | 6 Months | Clinical resolution of skin lesion at 4 weeks and at least four-fold decline in Rapid Plasma Reagin titre or seroreversion at 6-month (compared to baseline) in T.pallidum subsp. pertenue Polymerase Chain Reaction-negative. |
| Number of Participants With Adverse Events | 6 months | To compare the incidences and relative risk of all Adverse Events (AEs), including treatment-related AEs, Serious Adverse Events (SAEs) and grade 3-4 toxicity in patients treated with AZT20 and AZT30 regimens |
Countries
Ghana, Papua New Guinea, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AZT30 Single dose of azithromycin at a dose of 30mg/kg - max 2 Grams
Azithromycin: Comparison of two different dosing strategies for the treatment of yaws | 291 |
| AZT20 Single dose of azithromycin at a dose of 20mg/kg - max 1 Grams
Azithromycin: Comparison of two different dosing strategies for the treatment of yaws | 292 |
| Total | 583 |
Baseline characteristics
| Characteristic | AZT30 | AZT20 | Total |
|---|---|---|---|
| Age, Continuous | 10 years | 10 years | 10 years |
| Region of Enrollment Ghana | 199 participants | 201 participants | 400 participants |
| Region of Enrollment Papua New Guinea | 92 participants | 91 participants | 183 participants |
| Sex: Female, Male Female | 83 Participants | 88 Participants | 171 Participants |
| Sex: Female, Male Male | 208 Participants | 204 Participants | 412 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 291 | 15 / 292 |
| serious Total, serious adverse events | 0 / 291 | 0 / 292 |
Outcome results
Primary
Number of Participants With Clinical and Serological Cure
Clinical resolution of skin lesion at 4 weeks and at least four-fold decline in Rapid Plasma Reagin titre or seroreversion at 6-month (compared to baseline) in T.pallidum subsp. pertenue Polymerase Chain Reaction-confirmed subjects with yaws.
Time frame: 6 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZT30 | Number of Participants With Clinical and Serological Cure | 68 Participants |
| AZT20 | Number of Participants With Clinical and Serological Cure | 61 Participants |
Secondary
Number of Participants With Adverse Events
To compare the incidences and relative risk of all Adverse Events (AEs), including treatment-related AEs, Serious Adverse Events (SAEs) and grade 3-4 toxicity in patients treated with AZT20 and AZT30 regimens
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZT30 | Number of Participants With Adverse Events | 12 Participants |
| AZT20 | Number of Participants With Adverse Events | 14 Participants |
Secondary
Number of Participants With Clinical and Serological Cure in Latent Yaws
Clinical resolution of skin lesion at 4 weeks and at least four-fold decline in Rapid Plasma Reagin titre or seroreversion at 6-month (compared to baseline) in T.pallidum subsp. pertenue Polymerase Chain Reaction-negative.
Time frame: 6 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZT30 | Number of Participants With Clinical and Serological Cure in Latent Yaws | 65 Participants |
| AZT20 | Number of Participants With Clinical and Serological Cure in Latent Yaws | 73 Participants |