Single-dose Azithromycin for the Treatment of Yaws

NCT01382004 | Completed Phase 3

• 1 other identifier: YAWS-AZ01
• Study Type: interventional
• Target: 255
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Yaws; Treponema Infection; Neglected Tropical Disease

Keywords

Neglected diseases; Children

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months follow up

Secondary Outcomes (2)

• clinical cure

  6 months

• 3 months cure rate

  3 months

Study Arms (2)

Penicillin-G-Benzathine

ACTIVE COMPARATOR

penicillin-G-Benzathine : 50,000 UI/Kg single dose(maximum 2.4 million units IM)

Drug: Penicillin-G-benzathine

Azithromycin

EXPERIMENTAL

Azithromycin: 30 mg/kg single dose (Maximum: 2.000 mg.)

Drug: Azithromycin

Interventions

Penicillin-G-benzathine DRUG

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

Also known as: Zithromax, Bicillin LA

Penicillin-G-Benzathine

Azithromycin DRUG

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

Azithromycin

Eligibility Criteria

• Age: 6 Months - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Lihir Medical Centre: lead
• Centre For International Health: collaborator

Study Sites (1)

Lihir Medical Centre

Kavieng, New Ireland Province, 034, Papua New Guinea

Location

Related Publications (1)

• 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.

  PMID: 22240407 DERIVED

MeSH Terms

Conditions

Yaws; Treponemal Infections; Neglected Diseases

Interventions

Penicillin G; Azithromycin; Penicillin G Benzathine

Condition Hierarchy (Ancestors)

Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Skin Diseases, Bacterial; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones

Study Officials

• Quique Bassat, MD, PhD

  Centre for International Health Research/Hospital Clínic/University of barcelona

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: June 23, 2011
• First Posted: June 27, 2011
• Study Start: September 1, 2010
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: April 13, 2012

Record last verified: 2012-04

Locations

PA (1)