Treatment of Typhoid Fever with Azithromycin and Cefixime in South Asia

Azithromycin and Cefixime Combination Versus Azithromycin Alone for the Out-patient Treatment of Clinically Suspected or Confirmed Uncomplicated Typhoid Fever in South Asia; a Randomised Controlled Trial

This study is testing if the antibiotics azithromycin and cefixime can effectively treat uncomplicated typhoid fever in South Asia, especially in light of growing drug resistance.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 1500 (estimated)
• Ages: 2 Years to 65 Years
• Sex: All
• Sponsor: Oxford University Clinical Research Unit, Vietnam (Academic / other)
• Locations: 1 site (Lalitpur, Bagmati)
• Trial ID: NCT04349826 on ClinicalTrials.gov

What this trial studies

This trial investigates the effectiveness of azithromycin and cefixime in treating uncomplicated typhoid fever in South Asia, where antimicrobial resistance is a growing concern. Patients aged 2 to 65 years with a documented fever for at least 72 hours and no clear focus of infection will be enrolled. The study aims to compare the outcomes of these treatments against a placebo to determine their efficacy in reducing illness duration and preventing complications. The trial is crucial due to the emergence of resistant strains of typhoid, particularly in Pakistan.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals aged 2 to 65 years with a fever lasting at least 72 hours and no clear signs of other infections.

Not a fit: Patients with severe symptoms indicating focal infections or those with a history of fever lasting more than 14 days will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide effective treatment options for typhoid fever, reducing recovery time and healthcare costs for patients.

How similar studies have performed: Other studies have shown varying success with similar antimicrobial treatments for typhoid, but the emergence of resistant strains makes this approach particularly novel and urgent.

Eligibility criteria

Inclusion Criteria:

* A history of fever at presentation for ≥ 72 hours and a documented fever (≥37.5oC (axillary) or ≥38oC (oral))
* Age ≥ 2 years (and ≥ 10kg) to 65 years
* No clear focus of infection on initial clinical evaluation
* Malaria rapid Diagnostic test( RDT) negative; dengue nonstructural protein(NS) 1 RDT negative; scrub typhus RDT negative; c-reactive protein(CRP) rapid test ≥10 mg/L
* Able to take oral treatment
* Able to attend for follow-up and can be contacted by telephone
* Written fully informed consent to participate in the study including assent for children in addition to parental/legal guardian consent.

Exclusion Criteria:

* History of fever for \>14 days
* Pregnant or positive pregnancy test or breast-feeding
* Presence of clinical symptoms or signs indicating a focal infection such as pneumonia; urinary infection, meningitis, eschar
* Obtundation, haemodynamic shock, visible jaundice, gastrointestinal bleeding or any signs of severe disease that may require immediate hospitalisation
* Being treated for TB or HIV or severe acute malnutrition
* Patients with cardiac disease
* Patient requiring intravenous antibiotics for any reason
* Previous history of hypersensitivity to any of the treatment options
* Either of the trial drugs are contraindicated for any reason (e.g. drug interactions)
* Has received azithromycin or cefixime in the last five days
* Receiving another antimicrobial and responding clinically to the treatment as judged by the attending clinician.

Where this trial is running

Lalitpur, Bagmati

• Patan Hospital — Lalitpur, Bagmati, Nepal (Recruiting)

Study contacts

• Principal investigator: Buddha Basnyat, MBBS,Msc,MD — University of Oxford
• Study coordinator: Buddha Basnyat, MBBS,Msc,MD

Conditions Typhoid Fever; Uncomplicated Typhoid Fever; Azithromycin; Cefixime; treatment failure