Typhoid Fever: Combined vs. Single Antibiotic Therapy

Typhoid Fever Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02224040
• Other study ID #: 64/12
• Status: Recruiting
• Phase: Phase 4
• First received: August 21, 2014
• Last updated: August 26, 2014
• Start date: August 2013
• Est. completion date: August 2015

Study information

• Verified date: August 2014
• Source: Sheba Medical Center
• Contact: Eli Schwartz, MD, DTMH
• Phone: +97235308456
• Email: Eli.schwartz[@]sheba.health.gov.il
• Is FDA regulated: No
• Health authority: Nepal: Health Research Council
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: August 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fever
• Typhoid Fever

Intervention

Drug:
• ceftriaxone

• ceftriaxone and azithromycin

• azithromycin

• azithromycin and cefixime

Locations

Country	Name	City	State
Nepal	Dhulikhel hospital	Dhulikhel

Sponsors (1)

Lead Sponsor	Collaborator
Sheba Medical Center

Country where clinical trial is conducted

Nepal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fever clearance time	Time to fever clearance will be measured and will be defined as an oral temperature that is below 37.50 C	One month	No
Secondary	Treatment failure	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.	One month	No