Evaluation of an Intensive 3-round MDA Strategy Towards Yaws Eradication

NCT03490123 | Completed Phase 4

• 1 other identifier: Yaws3
• Study Type: interventional
• Target: 56,000
• Locations: 1 country
• Sites: 1

Brief Summary

The current principle of yaws eradication (the Morges strategy) is based on single round mass drug administration (MDA) of azithromycin (AZI) called total community treatment (TCT) followed by targeted treatment of active cases every 6 months to detect and treat cases and contacts called total targeted treatment (TTT). Studies done in Papua New Guinea (PNG) show that 1 round of MDA will probably not suffice to stop transmission of infection. It may be preferable to conduct 3 rounds of MDA prior to the switch to TTT because of high coverage requirements to achieve elimination, particularly of latent cases. The investigators plan to determine whether 3 rounds of MDA are more effective for reaching yaws elimination. This research is needed to guide national programmatic implementation and needs to be done as soon as possible to scale up the program in the country. The aim of this proposal is to ascertain the number of rounds of MDA with AZI to be included in an improved strategy towards yaws eradication. The study will be implemented in 38 wards of New Ireland Province (NIP). The investigators will compare two different distribution strategies of MDA: (A) strategy with 3 biannual rounds of MDA and (B) a single mass treatment round of MDA followed by targeted treatment of cases and contacts. The investigators will also monitor the risk of appearance of antimicrobial resistance in Treponema pertenue.

Conditions

Yaws

Keywords

Azithromycin; Endemic treponematoses; Mass drug administration; Eradication; Papua New Guinea

Outcome Measures

Primary Outcomes (1)

• Prevalence of active and of latent yaws at 18 months

  Prevalence of active yaws confirmed by PCR at 18 months and prevalence of latent yaws determined by reaginic and non-reaginic positive DPP tests at 18 months

  18 months

Secondary Outcomes (1)

• Appearance of macrolide resistant yaws strains across the study population

  18 months

Study Arms (2)

Intervention

EXPERIMENTAL

Repeated total community treatment, TCT with study drug: Azithromycin tablets, 30mg/Kg (maximum 2g), a single dose every 6 months, for 12 months (3 doses). Study interventions are: R1-Total community treatment with azithromycin, R2-Total community treatment with azithromycin, R3-Total community treatment with azithromycin.

Drug: R1-Total community treatment with azithromycin; Drug: R2-Total community treatment with azithromycin; Drug: R3-Total community treatment with azithromycin

Control

ACTIVE COMPARATOR

Single total community treatment, TCT, with study drug: Azithromycin tablets, 30mg/Kg (maximum 2g), a single, at month 0 (1 dose); followed by two total targeted treatment, TTT, with study drug: Azithromycin tablets, 30mg/Kg (maximum 2g), a single, at months 6 and 12. Study interventions are: R1-Total community treatment with azithromycin, R2-Total targeted treatment with azithromycin, R3-Total targeted treatment with azithromycin.

Drug: R1-Total community treatment with azithromycin; Drug: R2-Total targeted treatment with azithromycin; Drug: R3-Total targeted treatment with azithromycin

Interventions

R1-Total community treatment with azithromycin DRUG

At month 0, all study participants (regardless of their yaws status) will receive 30 mg/Kg (maximum 2 g) of azithromycin orally under direct observation. Benzathine benzylpenicillin will be reserved as a backup for patients who cannot be treated with AZI, and who are not allergic to penicillin.

Also known as: R1-TCT

Control; Intervention

R2-Total community treatment with azithromycin DRUG

At month 6, all study participants (regardless of their yaws status) will receive 30 mg/Kg (maximum 2 g) of azithromycin orally under direct observation. Benzathine benzylpenicillin will be reserved as a backup for patients who cannot be treated with AZI, and who are not allergic to penicillin.

Also known as: R2-TCT

Intervention

R3-Total community treatment with azithromycin DRUG

At month 12, all study participants (regardless of their yaws status) will receive 30 mg/Kg (maximum 2 g) of azithromycin orally under direct observation. Benzathine benzylpenicillin will be reserved as a backup for patients who cannot be treated with AZI, and who are not allergic to penicillin.

Also known as: R3-TCT

Intervention

R2-Total targeted treatment with azithromycin DRUG

At 6 months, study participants will be screened for active yaws. Participants with yaws and their contacts will receive 30 mg/Kg (maximum 2 g) of azithromycin orally under direct observation. Benzathine benzylpenicillin will be reserved as a backup for patients who cannot be treated with AZI, and who are not allergic to penicillin.

Also known as: R2-TTT

Control

R3-Total targeted treatment with azithromycin DRUG

At 12 months, study participants will be screened for active yaws. Participants with yaws and their contacts will receive 30 mg/Kg (maximum 2 g) of azithromycin orally under direct observation. Benzathine benzylpenicillin will be reserved as a backup for patients who cannot be treated with AZI, and who are not allergic to penicillin.

Also known as: R3-TTT

Control

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• all people resident or not in wards in the study region present at time of implementation or in subsequent surveys

You may not qualify if:

• Children younger than 6 months
• Known allergy to macrolide antibiotics
• Refusal at village or individual levels

Sponsors & Collaborators

• Lihir Medical Centre: lead
• Barcelona Institute for Global Health: collaborator
• National Department of Health of Papua New Guinea: collaborator
• World Health Organization: collaborator
• University of Masarykova: collaborator
• Harvard School of Public Health (HSPH): collaborator

Study Sites (1)

Namatanai Rural Hospital

Kavieng, New Ireland Province, 08912, Papua New Guinea

Location

Related Publications (3)

• Mitja O, Godornes C, Houinei W, Kapa A, Paru R, Abel H, Gonzalez-Beiras C, Bieb SV, Wangi J, Barry AE, Sanz S, Bassat Q, Lukehart SA. Re-emergence of yaws after single mass azithromycin treatment followed by targeted treatment: a longitudinal study. Lancet. 2018 Apr 21;391(10130):1599-1607. doi: 10.1016/S0140-6736(18)30204-6. Epub 2018 Feb 7.

  PMID: 29428183 BACKGROUND

• Mitja O, Houinei W, Moses P, Kapa A, Paru R, Hays R, Lukehart S, Godornes C, Bieb SV, Grice T, Siba P, Mabey D, Sanz S, Alonso PL, Asiedu K, Bassat Q. Mass treatment with single-dose azithromycin for yaws. N Engl J Med. 2015 Feb 19;372(8):703-10. doi: 10.1056/NEJMoa1408586.

  PMID: 25693010 BACKGROUND

• John LN, Beiras CG, Houinei W, Medappa M, Sabok M, Kolmau R, Jonathan E, Maika E, Wangi JK, Pospisilova P, Smajs D, Ouchi D, Galvan-Femenia I, Beale MA, Giacani L, Clotet B, Mooring EQ, Marks M, Vall-Mayans M, Mitja O. Trial of Three Rounds of Mass Azithromycin Administration for Yaws Eradication. N Engl J Med. 2022 Jan 6;386(1):47-56. doi: 10.1056/NEJMoa2109449.

  PMID: 34986286 DERIVED

MeSH Terms

Conditions

Yaws

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Treponemal Infections; 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

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Data collection teams separate from the teams responsible for MDA and screening.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Model Details: Community intervention study

Study Record Dates

• First Submitted: March 29, 2018
• First Posted: April 6, 2018
• Study Start: April 16, 2018
• Primary Completion: April 1, 2020
• Study Completion: April 1, 2020
• Last Updated: June 23, 2021

Record last verified: 2021-06

Locations

PA (1)