A Phase 4 interventional study of Azithromycin and Cefixime in Typhoid Fever, sponsored by Oxford University Clinical Research Unit, Vietnam. Completed at 1 site in Nepal. Open to participants aged 2 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-01-15.
Sponsored by Oxford University Clinical Research Unit, Vietnam · Phase 4, Interventional, and Treatment
Typhoid and paratyphoid (enteric) fever affects more than 11 million children and adults globally each year including 7 million in South Asia. Up to 1% of patients who get typhoid may die of the disease and, in those that survive, a prolonged period of ill health and catastrophic financial cost to the family may follow. In the last 20 years, treatment of typhoid fever with a 7-day course of a single oral antimicrobial, such as ciprofloxacin, cefixime or azithromycin, given in an out-patient setting has led to patient recovery in 4 to 6 days without the need for expensive hospitalization. Increasing antimicrobial resistance in Asia and sub-Saharan Africa, threatens the effectiveness of these treatments and increases the risk of prolonged illness and severe disease. The recent emergence of a particularly resistant typhoid strain in Pakistan, and subsequent international spread, adds urgency to this problem and Salmonella is now listed as a high (Priority 2) pathogen by world health organisation.
Treatment with combinations of antimicrobials may be more effective for treating typhoid fever and mitigate the problems of resistance. This suggestion is based on expert opinion but not backed up by good quality evidence. The ACT-South Asia study aims to compare a combination of azithromycin and cefixime with azithromycin alone in the outpatient treatment of clinically suspected and confirmed uncomplicated typhoid fever. The total recruitment will be 1500 patients across sites in Bangladesh, India, Nepal and Pakistan. A placebo (sugar pill) will be used instead of cefixime in the single drug arm so that neither the patient nor the study team know which patient is receiving which treatment.Investigators will assess whether treatment outcomes are better with the combination after one week of treatment and at one and three month follow-up. Both antimicrobials are widely used and have excellent safety profiles. If the combination treatment is better than the single antibiotic treatment, this will be an important result for patients across South Asia and other typhoid endemic areas. This study will additionally investigate the financial implications for families and health system.
76 studies on the registry are indexed under Typhoid Fever; 11 are open to participants now.
This study's enrollment of 2,150 is above the median of 147 across 65 interventional studies indexed under Typhoid Fever.
Browse Typhoid Fever studies →Oxford University Clinical Research Unit, Vietnam is the lead sponsor of 37 studies on the registry; 3 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Azithromycin 20mg/kg/day oral dose once daily (maximum 1gm/day) AND Cefixime 20-30mg/kg/day oral dose in two divided doses (maximum 400mg bd) for 7 days.
Drug: Azithromycin · Drug: Cefixime
Azithromycin 20mg/kg/day oral dose once daily (Max 1gm/day) for 7 days AND Cefixime-matched placebo for 7 days.
Drug: Azithromycin · Drug: Placebo
Azithromycin 20 mg/kg/day for 7 days
cefixime 20-30 mg/kg/day for 7 days
cefixime-matched placebo for 7 days
Treatment Failure
A composite outcome of treatment failure by the 28th day after the initiation of treatment will be defined by either of the following events: 1.Clinical failure: persistence of fever on day 7 (168 h) post treatment initiation OR The need for rescue treatment as judged by the Trial Clinician OR The development of any complication (e.g., clinically significant bleeding, fall in the Glasgow Coma Scale score, perforation of the gastrointestinal tract) OR Syndromic enteric fever relapse within 28 days of initiation of treatment. 2.Microbiological failure: a positive blood-culture for S. Typhi or S. Paratyphi on day 7 of treatment regardless of the presence of fever (microbiological failure) OR blood culture-confirmed typhoid fever relapse within 28 days of initiation of treatment.
Time frame: Within 28 days of treatment initiation
Fever clearance time (FCT) in patients in each treatment arm
The FCT will be the time from the first dose of a study drug until a temperature of \< 37.5°C (axillary); \< 38.0°C (oral) has been achieved
Time frame: at least 2 days
Time from onset of treatment to treatment failure
The time to treatment failure will be the time from the first dose of a study drug until an event occurs defined as a treatment failure
Time frame: Within 28 days of treatment initiation
Time from symptom onset to treatment failure
The time to treatment failure will be the time from the day of the first symptom until an event occurs defined as a treatment failure
Time frame: Within 28 days of treatment initiation
Adverse event
Adverse events will be graded (grade 3/4 adverse events, serious adverse events, adverse events of any grade leading to modification of study drug dose or interruption/early discontinuation);
Time frame: Within 90 days
faecal carriage of S.Typhi or S.Paratyphi
Positive culture of faeces sample for S.Typhi or S.Paratyphi
Time frame: One and three month follow-up
cost effectiveness of treatment
The incremental cost-effectiveness ratio (ICER) will comprise of the total costs per case, real outpatient and in-patient costs, total direct and indirect costs for the family and healthcare system and health outcomes converted to Disability Adjusted Life Years (DALYs). The cost per DALY averted will be compared against multipliers of the gross domestic product/capita in each of the four countries to establish the cost-effectiveness of the combination regimen.
Time frame: Initiation of treatment and one month follow-up visit
Plan to share: Yes — Anonymised individual participant data will be made available to researcher and public as supporting material via open access journal and /or upon request by qualified research group.
Ran from May 2021 to primary completion in Dec 2025, 55 months.
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Studies of the drug tested here: Cefixime
Oxford University Clinical Research Unit, Vietnam