Shortening treatment for Buruli ulcer using a new drug combination

Beta-Lactam Containing Regimen for the Shortening of Buruli Ulcer Disease Therapy: Comparison of 8 Weeks Standard Therapy (Rifampicin Plus Clarithromycin) vs. 4 Weeks Standard Plus Amoxicillin/Clavulanate Therapy [RC8 vs. RCA4]

This study is testing a new 4-week treatment for Buruli ulcer using a different drug combination to see if it can heal patients faster than the usual 8-week therapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 140 (estimated)
• Ages: 5 Years to 70 Years
• Sex: All
• Sponsor: Fundacion Agencia Aragonesa para la Investigacion y Desarrollo (ARAID) (Academic / other)
• Locations: 3 sites (Allada and 2 other locations)
• Trial ID: NCT05169554 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of a new treatment regimen for Buruli ulcer, a neglected tropical disease caused by Mycobacterium ulcerans. The study compares the standard 8-week therapy of rifampicin and clarithromycin with a new combination that includes amoxicillin/clavulanate for a shorter 4-week duration. The goal is to improve healing times and reduce the treatment burden on patients, particularly children in sub-Saharan Africa. The trial will include patients with a clinical diagnosis of Buruli ulcer who meet specific eligibility criteria.

Who should consider this trial

Good fit: Ideal candidates are individuals of all genders with a new clinical diagnosis of Buruli ulcer who are between 5 and 70 years old and have a normal ECG.

Not a fit: Patients under 5 years old, over 70 years old, or those with a history of severe hypersensitivity reactions to the study drugs will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the duration of therapy for Buruli ulcer, improving patient compliance and outcomes.

How similar studies have performed: Previous studies have shown promising results with similar drug combinations against Mycobacterium ulcerans, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

All patients (both genders) with a new very likely or likely (WHO scoring criteria) clinical diagnosis of BU (all categories: I, II, III) and normal electrocardiogram (ECG) at baseline giving informed consent will be included in the study, as agreed by study site treatment team led by the lead clinicians.

Exclusion Criteria:

* Children \< 5 years and adults \>70 years.
* Children in foster care.
* Patients weighing less than 11 kilograms.
* Pregnancy positive (urine test: beta-HCG positive).
* Previous treatment of Buruli ulcer, tuberculosis or leprosy with at least one of the study drugs.
* Patients with diagnose leprosy or tuberculosis disease.
* Hypersensitivity to at least one of the study drugs or to any of the excipients.
* History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam agent (e.g. a cephalosporin, carbapenem or monobactam).
* History of jaundice/hepatic impairment due to amoxicillin/clavulanic acid or rifampicin.
* Patients with history of treatment with macrolide or quinolone antibiotics, anti-tuberculosis medication, or immuno-modulatory drugs including corticosteroids within one month.
* Patients currently receiving treatment with any drugs likely to interact with the study medications, i.e. anticoagulants, cyclosporine, phenytoin or phenobarbitone. Users of oral contraceptives should be notified that such contraceptive is less reliable if taken with rifampicin; additional (mechanical) contraceptive methods will be discussed with the study participant (Appendix 5).
* Patients with HIV co-infection.
* Patients with QTc prolongation \>450 ms on ECG or on other medication known to prolong the QTc interval. In this case, if suspected of BU disease, patients will be offered 8-weeks rifampicin plus streptomycin therapy.
* Patients unable to take oral medication or having gastrointestinal disease likely to interfere with drug absorption.
* Patients with history or having current clinical signs of ascites, jaundice, myasthenia gravis, renal dysfunction (known or suspected), diabetes mellitus, and severe immune compromise, or evidence of tuberculosis, or leprosy; terminal illness (e.g., metastasized cancer), haematological malignancy, chronic liver disease, abnormal liver function test and coronary artery disease or any other condition that would preclude enrolment into the study in the study physician's opinion.
* Evidence of a clinically significant (as judged by the Investigator) condition or abnormality (other than the indication being studied) that might compromise safety or the interpretation of trial efficacy or safety endpoints
* Patients with known or suspected bowel strictures who cannot tolerate clarithromycin.
* Patients with a mental health condition that is likely to interfere with compliance with the study protocol in the opinion of the study physician.
* Patients (or parent/legal representative) who are not willing to give informed consent or withdrawal of consent.
* Specific exclusion criteria for the PK sub-study are patients less than 15 years old or less than 40 kg or with renal impairment with a creatinine level higher than the normal one in Benin (7-14 mg/L).

Where this trial is running

Allada and 2 other locations

• Centre de Dépistage et de Traitement de l'Ulcère de Buruli (CDTUB) (Centers for Detection and Treatment of Buruli ulcer), Allada — Allada, Benin (Recruiting)
• Centre de Dépistage et de Traitement de l'Ulcère de Buruli (CDTUB) (Centers for Detection and Treatment of Buruli ulcer), Lalo — Lalo, Benin (Recruiting)
• Centre de Dépistage et de Traitement de l'Ulcère de Buruli (CDTUB) (Centers for Detection and Treatment of Buruli ulcer), Pobè — Pobè, Benin (Recruiting)

Study contacts

• Study coordinator: Christian Johnson

Conditions Buruli Ulcer; Buruli ulcer; Neglected tropical disease; Treatment shortening; Drug combination; Amoxicillin/clavulanate; Clinical trial; Pharmacokinetic analysis