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Trial record 48 of 107 for:    ( Map: Nepal )

Typhoid Fever: Combined vs. Single Antibiotic Therapy

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ClinicalTrials.gov Identifier: NCT02224040
Recruitment Status : Unknown
Verified August 2014 by Prof. Eli Schwartz MD, DTMH, Sheba Medical Center.
Recruitment status was:  Recruiting
First Posted : August 22, 2014
Last Update Posted : August 27, 2014
Sponsor:
Information provided by (Responsible Party):
Prof. Eli Schwartz MD, DTMH, Sheba Medical Center

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.


Condition or disease Intervention/treatment Phase
Typhoid Fever Drug: ceftriaxone Drug: ceftriaxone and azithromycin Drug: azithromycin Drug: azithromycin and cefixime Phase 4

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Typhoid Fever: Combined vs. Single Antibiotic Therapy. A Prospective Randomized Controlled Study in Nepal.
Study Start Date : August 2013
Estimated Primary Completion Date : December 2014
Estimated Study Completion Date : August 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antibiotics Fever
Drug Information available for: Ceftriaxone

Arm Intervention/treatment
Experimental: Ceftriaxone I.V
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).
Drug: ceftriaxone
Experimental: Ceftriaxone I.V+Azithromycin P.O
The participants in this arm will receive the following drugs and dosages: adult: 2 g intravenous ceftriaxone and 500 mg oral azithromycin once a day. Pediatric: intravenous 75 mg/kg ceftriaxone once a day and oral 20 mg/kg azithromycin suspension once a 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).
Drug: ceftriaxone and azithromycin
Experimental: Azithromycin P.O
The participants in this arm will receive the following drug and dosage: adult: azithromycin oral 500 mg once a day. Pediatric: oral 20 mg/kg azithromycin suspension once a day (maximum dose 1000 mg/day). Patients will receive antibiotic treatment until defervescence and for 3 days afterwards.
Drug: azithromycin
Experimental: Azithromycin P.O+Cefixime P.O
The participants in this arm will receive the following drugs and dosages: adult: 500 mg azithromycin and 400 mg cefixime. Pediatric: oral 20 mg/kg azithromycin suspension once a day and oral 10 mg/kg cefixime. Patients will receive antibiotic treatment until defervescence and for 3 days afterwards.
Drug: azithromycin and cefixime



Primary Outcome Measures :
  1. Fever clearance time [ Time Frame: One month ]
    Time to fever clearance will be measured and will be defined as an oral temperature that is below 37.50 C


Secondary Outcome Measures :
  1. Treatment failure [ Time Frame: One month ]
    Secondary endpoints will be treatment failure (defined as the need to switch antibiotic treatment according to physician's decision such as high grade fever after 5 days of treatment, appearance of typhoid complications under the treatment), clearance of bacteremia, development of typhoid-related complications, late relapse, fecal carriage and adverse drug reactions.



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Ages Eligible for Study:   2 Years to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02224040


Contacts
Contact: Eli Schwartz, MD, DTMH +97235308456 Eli.schwartz@sheba.health.gov.il

Locations
Nepal
Dhulikhel hospital Recruiting
Dhulikhel, Nepal, 11008
Contact: Sudeep Shrestha, M.D       itsactionpotential@gmail.com   
Sponsors and Collaborators
Sheba Medical Center
Investigators
Principal Investigator: Eli Schwartz, MD, DTMH Sheba Medical Center

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof. Eli Schwartz MD, DTMH, Principal Investigator of the geographic clinical, Sheba Medical Center
ClinicalTrials.gov Identifier: NCT02224040     History of Changes
Other Study ID Numbers: 64/12
First Posted: August 22, 2014    Key Record Dates
Last Update Posted: August 27, 2014
Last Verified: August 2014

Additional relevant MeSH terms:
Fever
Typhoid Fever
Body Temperature Changes
Signs and Symptoms
Salmonella Infections
Enterobacteriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Anti-Bacterial Agents
Ceftriaxone
Cefixime
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents