Repurposing Clinically Approved Drugs for Yaws with an Insight Into the Cutaneous Ulcer Disease Syndrome (Trep-AByaws)

NCT ID: NCT05764876

Last Updated: 2025-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 465 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-14
• Study Completion Date: 2024-12-01

Brief Summary

The goal of this clinical trial is to test the non inferiority of linezolid compared with azithromycin as a treatment for yaws . The main questions it aims to answer are: can linezolid cure active yaws, and can linezolid cure latent yaws. Participants with serologically confirmed yaws will be randomized to receive linezolid (experimental) or azithromycin (control group) treatment and followed up to assess clinical resolution.

Detailed Description

The current principle of yaws eradication is based on a single round of mass drug administration of azithromycin (AZI) called total community treatment (TCT) followed by targeted treatment of active cases and close contacts every 6 months called total targeted treatment (TTT). Studies done in Papua New Guinea have shown that 3 rounds of TCT are preferable to 1 TCT followed by TTT rounds because it results in higher overall coverage, particularly of latent cases. In the context of repeated rounds of TTT and multiple rounds of TCT, resistance to AZI has ben detected on 5 patients with yaws Recent studies have been successful on the culture of Treponema pallidum (syphilis and yaws), therefore investigators are now able to identify more potential treatment for yaws and syphilis.

Yaws is one of the major causes of the Cutaneous Ulcer Disease (CUD) syndrome. The CUD syndrome is a painful and debilitating condition, endemic to remote tropical regions with poor sanitation and limited health care access affecting children mainly. In Papua New Guinea it is caused by a range of unknown and some known pathogens besides yaws that are not easily distinguished on clinical diagnosis. New information on the causative agents of the CUD syndrome is needed to facilitate its management with an integrated approach.

The aim of the project is to provide evidence supporting (or rejecting) the hypothesis that the use of linezolid (LZD) can be an alternative treatment to cure yaws corroborated by clinical, serological, and molecular methods. LZD is a very safe drug that has been delivered to adults and children for the treatment of cutaneous infections all over the world. Investigators will compare two different treatments: (A) linezolid (LZD) and (B) azithromycin (AZI). In addition, the investigators plan to contribute to characterize the etiology of the CUD syndrome. The study will be implemented in selected wards of the Islands Region of Papua New Guinea.

Conditions

Yaws; Cutaneous Ulcer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Azithromycin

Participants in the control arm will receive standard treatment for yaws which azithromycin .

Group Type: ACTIVE_COMPARATOR

Azithromycin Oral Tablet

Intervention Type: DRUG

Oral tablet of azithromycin 30mg/kg maximum 2gr single dose.

Linezolid

Participants in the experimental arm will receive oral linezolid treatment.

Group Type: EXPERIMENTAL

Linezolid Oral Tablet

Intervention Type: DRUG

Oral tablet of linezolid 10mg/kg every 8 hours for 7 days.

Interventions

Linezolid Oral Tablet

Oral tablet of linezolid 10mg/kg every 8 hours for 7 days.

Intervention Type: DRUG

Azithromycin Oral Tablet

Oral tablet of azithromycin 30mg/kg maximum 2gr single dose.

Intervention Type: DRUG

Other Intervention Names

Zyvox, Zyvoxid; Zithromax

Eligibility Criteria

Inclusion Criteria

1. Participants 5-18 years identified during an active case search program at the elementary, primary and secondary schools in the Islands Region.

2. CUD syndrome suspected due to yaws: one or more ulcerative or nodular or papilloma skin lesion of more than 1 cm in diameter.

3. Positive treponemal (T1) and non-treponemal (T2) serology by Chembio dual path platform (DPP) syphilis screen & confirm assay (DPP test).

4. Accepted and signed informed consent.

5. Ability to comply with the requirements of the study protocol including follow up visits.

Exclusion Criteria

1. Children younger than 5 years old.

2. Clinical late-stage possible yaws: destructive osteitis (rhinopharyngitis gangosa, sabre shins) or gummous nodules.

3. Known allergy to LZD or AZI antibiotics.

4. Pregnant or breastfeeding women.

5. Refusal at ward level or village chief (for village inclusion), or refusal of individual or guardian (for individual inclusion).

6. Have taken any antibiotics with potential activity against TPE within the last 7 days prior to randomization (i.e., beta lactams, cephalosporines, macrolides, tetracyclines).

7. Uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, carcinoid syndrome, bipolar disorder, incapacitating psycho-affective disturbance, acute confusional state.

8. Renal function impairment requiring hemodialysis.

9. Current treatment with any drugs likely to interact with the study medication

10. Symptomatic concomitant infection requiring antibiotic treatment potentially active against TPE.

11. Having received treatment for yaws in the last 6 months.

12. Patients who are unable to take oral medication or having a gastrointestinal disease likely to interfere with drug absorption (including malnutrition and stomach flu).

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Department of Health, Papua New Guinea

UNKNOWN

Sponsor Role: collaborator

School of Medicine and Health Sciences, University of Papua New Guinea

UNKNOWN

Sponsor Role: collaborator

Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

OTHER

Sponsor Role: lead

Responsible Party

Oriol Mitja

Associate Professor, Infectious Diseases and Global Health

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Camila Beiras

Role: STUDY_DIRECTOR

Fundació Lluita contra les Infeccions

Locations

National Department of Health

Port Moresby, , Papua New Guinea

Countries

Papua New Guinea

Other Identifiers

Trep-AByaws

Identifier Type: -

Identifier Source: org_study_id