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

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Brief Title

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

Official Title

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

Brief 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.
    


Study Phase

Phase 4

Study Type

Interventional


Primary Outcome

Treatment Failure

Secondary Outcome

 Fever clearance time (FCT) in patients in each treatment arm

Condition

Typhoid Fever

Intervention

Azithromycin

Study Arms / Comparison Groups

 Azithromycin+Cefixime
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

1500

Start Date

September 1, 2020

Completion Date

August 31, 2023

Primary Completion Date

September 1, 2022

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.
      

Gender

All

Ages

2 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

Buddha Basnyat, MBBS,Msc,MD, +977-9851034187, [email protected]



Administrative Informations


NCT ID

NCT04349826

Organization ID

25NP


Responsible Party

Sponsor

Study Sponsor

Oxford University Clinical Research Unit, Vietnam

Collaborators

 University of Oxford

Study Sponsor

Buddha Basnyat, MBBS,Msc,MD, Principal Investigator, University of Oxford


Verification Date

April 2020