The Azithromycin and Cefixime Treatment of Typhoid in South Asia Trial (ACT-South Asia Trial)

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

2150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-23

Study Completion Date

2025-12-31

Brief Summary

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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.

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Detailed Description

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Conditions

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Typhoid Fever

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Double Blind

Study Groups

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Azithromycin+Cefixime

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.

Group Type ACTIVE_COMPARATOR

Azithromycin

Intervention Type DRUG

Azithromycin 20 mg/kg/day for 7 days

Cefixime

Intervention Type DRUG

cefixime 20-30 mg/kg/day for 7 days

Azithromycin+placebo

Azithromycin 20mg/kg/day oral dose once daily (Max 1gm/day) for 7 days AND Cefixime-matched placebo for 7 days.

Group Type PLACEBO_COMPARATOR

Azithromycin

Intervention Type DRUG

Azithromycin 20 mg/kg/day for 7 days

Placebo

Intervention Type DRUG

cefixime-matched placebo for 7 days

Interventions

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Azithromycin

Azithromycin 20 mg/kg/day for 7 days

Intervention Type DRUG

Cefixime

cefixime 20-30 mg/kg/day for 7 days

Intervention Type DRUG

Placebo

cefixime-matched placebo for 7 days

Intervention Type DRUG

Eligibility Criteria

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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.

Minimum Eligible Age

2 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No