Comparison of Two Different Doses of Azithromycin for Treatment of Yaws

Study Overview
=================
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.

Official Title
-----------------
Randomized Controlled Trial Comparing Efficacy of Single Dose Treatment of Yaws With 20mg/kg Versus 30mg/kg of Azithromycin

Conditions
-----------------
Yaws

Intervention / Treatment
-----------------
* Drug: Azithromycin


Participation Criteria
=================
Eligibility Criteria
-----------------
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: Known allergy to azithromycin or macrolides. Treatment with long-acting penicillin or alternative antibiotic with activity against T. pallidum within the last 3 months (ceftriaxone, azithromycin or doxycycline, amoxicillin). Patients with current treatment with any drugs likely to interact with the study medication. Patients who are unable to take oral medication or having gastrointestinal disease likely to interfere with drug absorption. Patients who may not be able to comply with the requirements of the study protocol including follow up visits. Patients who are not willing to give informed consent (patient and/or parent/legal representative), or who withdraw consent.

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 16 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AZT30<br>Single dose of azithromycin at a dose of 30mg/kg - max 2 Grams | Drug: Azithromycin<br>* Comparison of two different dosing strategies for the treatment of yaws<br>|
| Experimental: AZT20<br>Single dose of azithromycin at a dose of 20mg/kg - max 1 Grams | Drug: Azithromycin<br>* Comparison of two different dosing strategies for the treatment of yaws<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6 Months | 
| 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 | 6 months |