The purpose of the study is to determine whether azithromycin or cotrimoxazole is the best empirical treatment for undifferentiated febrile illness in Nepal
Fever is one of the most common presenting symptoms of patients presenting to health centers in Nepal. Many of the times, it is difficult to diagnose the cause of the fever by initial history, clinical examination and basic laboratory tests and the patents are treated as presumed enteric fever or fever without focus needing antimicrobials. In fact there are various causes of similarly presenting febrile illnesses including typhoid, paratyphoid, murine typhus, scrub typhus etc. Many of the traditionally used drugs including fluoroquinolones are now resistant against enteric fever in south asia. Oral azithromycin is now commonly used to treat undifferentiated febrile illness and remains effective against enteric fever. Many physicians now also use co-trimoxazole as it was very commonly used in the treatment of enteric fever in the past. Resistance to co-trimoxazole emerged two decades ago, but has subsequently largely disappeared and nearly all Salmonella Typhi and Paratyphi A strains from Nepal are now susceptible. Anecdotal reports claim that it seems to work very well against undifferentiated febrile illness in Nepal; it is largely stocked in government health facilities and is a popular and cheap treatment option. Both azithromycin and co-trimoxazole are available in Nepal and are extensively used in the treatment of undifferentiated febrile illness. Therefore it is important to know the better oral option to treat enteric fever and other febrile illnesses and also to have an alternative oral treatment in case resistance to azithromycin emerges. The investigators purpose to conduct a head to head, parallel group, 1:1, double blinded randomized controlled trial to compare azithromycin and co-trimoxazole for the treatment of undifferentiated febrile illness and determine the best empirical treatment for undifferentiated febrile illness in Nepal.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
330
Nepal Civil Service Hospital
Kathmandu, Nepal
Patan Hospital
Kathmandu, Nepal
Fever clearance time
time from the first dose of a study drug until a temperature ≤37.5°C for at least 2 days
Time frame: at least 2 days
Fever failure
defined by fever clearance time (FCT) \>7 days post treatment initiation;
Time frame: over 7 days post treatment initiation
Need rescue treatment
Requirement for rescue treatment as judged by the Research Medical Officer (RMO) and Attending Physician (AP)
Time frame: within 63 days
Microbiological failure
Blood culture positivity for S. Typhi or an S. Paratyphi
Time frame: on day 7 of treatment
Relapse
Culture-confirmed or syndromic enteric fever relapse
Time frame: within 28 days of initiation of treatment
The development of any complication
any complication: e.g. clinically significant bleeding, fall in the Glasgow Coma Score, perforation of the gastrointestinal tract and hospital admission
Time frame: within 28 days of initiation of treatment
Time-to-treatment failure
the time from the first dose of treatment until the date of the earliest failure event
Time frame: within 63 days
Adverse events
grade 3/4 adverse events, serious adverse events, adverse events of any grade leading to modification of study drug dose or interruption/early discontinuation
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Time frame: within 63 days