Typhoid Fever: Combined vs. Single Antibiotic Therapy

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Brief Title

Typhoid Fever: Combined vs. Single Antibiotic Therapy

Official Title

Typhoid Fever: Combined vs. Single Antibiotic Therapy. A Prospective Randomized Controlled Study in Nepal.

Brief Summary

      The current study goal is to examine the effect of Cephalosporins, Azithromycin and the
      combination of both on typhoid fever therapy in endemic population.

      The investigator's hypothesize that the combination of azithromycin and ceftriaxone may prove
      superior to each drug, ceftriaxone or azithromycin, alone.
    

Detailed Description

      Typhoid Fever is a highly prevalent infection in the Indian subcontinent. Due to multidrug
      resistant strains in these areas, third generation cephalosporins, such as ceftriaxone, are
      the treatment of choice. However, the latter regimen exhibits a slow response with mean time
      of 5 to 7 days or even longer to defervescence, which could be attributed to poor penetration
      capability of the drug into cells, and thus difficulty to eradicate the bacteria from the
      intracellular niche.

      Attempts have been made to overcome this setback by introducing alternative antibiotic
      regimens, such as azithromycin. However studies comparing between azithromycin and a
      third-generation cephalosporin for the treatment of typhoid fever in adult population in the
      Indian subcontinent are lacking.

      Over the last few years our approach towards non-immunized travelers, who acquired typhoid
      fever in the Indian subcontinent, was to administer a combination therapy of intravenous
      ceftriaxone with oral azithromycin. The rationale of this dual regimen was its
      pharmacokinetic profile, which suggests a complimentary action of the two agents -
      ceftriaxone on the extracellular compartment and azithromycin on the intracellular
      compartment. Moreover, in our clinical experience, preliminary published data has proven
      combination therapy significantly superior to ceftriaxone alone albeit in a small group of
      travelers.

      In the current study the investigators intend to compare the efficacy of ceftriaxone vs.
      azithromycin and vs. combined therapy of both agents for the treatment of uncomplicated
      typhoid fever in terms of time to defervescence.

      4 different treatment strategies will be examined (as mentioned in the arm section). All
      participants will be checked for vital signs, will undergo physical examination, ECG,
      laboratory testing, blood, urine and stool culture and tests for susceptibility to
      antibiotics.
    

Study Phase

Phase 4

Study Type

Interventional


Primary Outcome

Fever clearance time

Secondary Outcome

 Treatment failure

Condition

Typhoid Fever

Intervention

ceftriaxone

Study Arms / Comparison Groups

 Ceftriaxone I.V
Description:  The participants in this arm will receive the following drug and dosage: adult: Ceftriaxone intravenous 2 gr once a day. Pediatric: intravenous 75 mg/kg ceftriaxone once a day (maximum dose 2.5 g/day). Patients will receive antibiotic treatment until defervescence and for 3 days afterwards. Patients will be hospitalized during the entire treatment course (including the afebrile period).

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

120

Start Date

August 2013

Completion Date

August 2015

Primary Completion Date

December 2014

Eligibility Criteria

        Inclusion Criteria:

          -  Blood culture-proven typhoid fever (S. typhi or S. paratyphi)

          -  Signed informed consent to participate in the study.

        Exclusion Criteria:

          -  Allergy to ceftriaxone or macrolides

          -  Major typhoid fever-associated complications

          -  Inability to swallow oral medication

          -  Underlying illness

          -  Pregnancy

          -  Lactation

          -  Treatment within the past 4 days with an antibiotic that may be effective against
             typhoid fever
      

Gender

All

Ages

2 Years - 80 Years

Accepts Healthy Volunteers

No

Contacts

Eli Schwartz, MD, DTMH, +97235308456, [email protected]

Location Countries

Nepal

Location Countries

Nepal

Administrative Informations


NCT ID

NCT02224040

Organization ID

64/12


Responsible Party

Principal Investigator

Study Sponsor

Sheba Medical Center


Study Sponsor

Eli Schwartz, MD, DTMH, Principal Investigator, Sheba Medical Center


Verification Date

August 2014