The Azithromycin and Cefixime Treatment of Typhoid in South Asia Trial (ACT-South Asia Trial)
Status:
Not yet recruiting
Trial end date:
2023-08-31
Target enrollment:
Participant gender:
Summary
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.
Phase:
Phase 4
Details
Lead Sponsor:
Oxford University Clinical Research Unit, Vietnam
Collaborators:
Department for International Development, United Kingdom Medical Research Council University of Oxford Wellcome Trust