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
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|
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|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
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).
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.
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
- 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
- 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.
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
|Contact: Eli Schwartz, MD, DTMH||+97235308456||Eli.firstname.lastname@example.org|
|Dhulikhel, Nepal, 11008|
|Contact: Sudeep Shrestha, M.D email@example.com|
|Principal Investigator:||Eli Schwartz, MD, DTMH||Sheba Medical Center|