Comparison of Two Different Doses of Azithromycin for Treatment of Yaws

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

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.

Study Overview

• Status: Completed
• Conditions: Yaws
• Intervention / Treatment: Drug: Azithromycin

• Study Type: Interventional
• Enrollment (Actual): 583
• Phase: Phase 3

Contacts and Locations

Study Locations

• Ghana
  • Eastern Region
    • Ayensuanor District, Eastern Region, Ghana
      • School Based Recruitment
    • Upper West Akyem, Eastern Region, Ghana
      • School Based Recruitment
    • West Akyem District, Eastern Region, Ghana
      • School Based Recruitment
  • Volta Region
    • Nkwanta North District, Volta Region, Ghana
      • School Based Recruitment
• Papua New Guinea
  • Madang Province
    • Karkar District, Madang Province, Papua New Guinea
      • Community Based Recruitment
  • New Ireland Province
    • Kavieng Subdistrict, New Ireland Province, Papua New Guinea
      • Community Based Recruitment
• United Kingdom
  • London, United Kingdom, WC1E 7HT
    • London School of Hygiene and Tropical Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: London School of Hygiene and Tropical Medicine
• Collaborators: Centers for Disease Control and Prevention; World Health Organization; Barcelona Institute for Global Health; Ghana Health Services; Kwame Nkrumah University of Science and Technology; Papua New Guinea Institute of Medical Research; Noguchi Memorial Institute for Medical Research; Papua New Guinea National Department of Health; University of Health and Allied Sciences, Ho, Volta Region, Ghana
• Investigators: Principal Investigator: David Mabey, London School of Hygiene and Tropical Medicine

Publications and helpful links

General Publications

• Marks M, Mitja O, Bottomley C, Kwakye C, Houinei W, Bauri M, Adwere P, Abdulai AA, Dua F, Boateng L, Wangi J, Ohene SA, Wangnapi R, Simpson SV, Miag H, Addo KK, Basing LA, Danavall D, Chi KH, Pillay A, Ballard R, Solomon AW, Chen CY, Bieb SV, Adu-Sarkodie Y, Mabey DCW, Asiedu K; study team. Comparative efficacy of low-dose versus standard-dose azithromycin for patients with yaws: a randomised non-inferiority trial in Ghana and Papua New Guinea. Lancet Glob Health. 2018 Apr;6(4):e401-e410. doi: 10.1016/S2214-109X(18)30023-8. Epub 2018 Feb 16.

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: January 17, 2015
• First Submitted That Met QC Criteria: January 17, 2015
• First Posted (Estimate): January 26, 2015

Study Record Updates

• Last Update Posted (Actual): October 31, 2018
• Last Update Submitted That Met QC Criteria: October 2, 2018
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Skin Diseases, Bacterial; Spirochaetales Infections; Treponemal Infections; Yaws; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: LSHTM-8832