Meropenem vs Azithromycin Efficacy in Case XDR Enteric Fever

NCT ID: NCT07314281

Last Updated: 2026-01-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-22
• Study Completion Date: 2025-12-31

Brief Summary

1. Primary Objective:

o To evaluate the efficacy of intravenous azithromycin compared with meropenem in the treatment of extensively drug-resistant (XDR) enteric fever.

2. Secondary Objectives:

• To evaluate the fever defervescence and Salmonella Typhi eradication
• To evaluate the cost-effectiveness of intravenous azithromycin versus meropenem in treating XDR enteric fever.

3. Exploratory Objectives:

• To evaluate the drug resistance against intravenous azithromycin versus in treating XDR enteric fever.

Detailed Description

Screening Period:

Patients with positive blood culture of XDR S. typhi underwent further screening for inclusion in study by physician. Before randomization, ECG monitoring, investigations including serum creatinine, liver function test, pregnancy test for married female participants will be done. If patient meet eligibility criteria and physician enrolled, randomization will be done and treatment will be allocated.

Treatment Period:

During treatment period, on D3 clearance blood culture will be sent to check bacterial eradication or sterility of blood. Temperature, blood pressure, pulse will be monitored three times a day. If D3 blood culture and sensitivity report is still positive, second clearance blood culture will be sent on D7. On D7 ECG and LFTs will reassessed. On D7 of treatment detailed clinical assessment will be done in order to evaluate improvement in clinical condition and need of therapy modification "Discontinuation of treatment" based on the list of all terms and condition including hypersensitivity reaction, any adverse event. Total treatment duration will be 14 days. Resolution of symptoms, fever defervescence and blood culture clearance will be consider as study end point.

Randomization and Blinding:

The participant meeting all the inclusion and exhibits no characteristics of exclusion criteria will be eligible to enroll in the study. The written informed consent will be taken and signed ICF will be obtained from participant. The participants will be enrolled in the study based on randomization. The randomization will be done by using randomization allocation software. The office of research and innovation (ORIC) personnel independent from the study will randomize and allocate treatment group. This is an open-label study; thus, both the investigators and participants will be aware of the treatment allocation after randomization. Principle investigator will enroll participants in collaboration with physician. The office of research and innovation (ORIC) personnel will develop envelope containing allocation sequence and treatment option either standard treatment or intervention treatment. Envelop will hand over to physician and will assign treatment option to participants.

Study treatment and Intervention:

For the standard care protocol, patients are initially treated with meropenem 1g intravenously every 8 hours. Once their condition stabilizes , treatment is transitioned to oral azithromycin. The transition involves administering a first dose of azithromycin 1g orally, followed by a daily dose of 500mg orally. Intravenous meropenem will continue until 24 hours after the patient's fever has resolved, after which the treatment will switch to oral azithromycin.

In the intervention group, patients begin with azithromycin 1g administered intravenously for the initial dose, followed by a daily dose of 500mg intravenously. When the patient's condition stabilizes, the treatment will transition to oral azithromycin, starting with a 1g oral dose and continuing with 500mg orally once daily. Intravenous azithromycin will be maintained until 24 hours after the patient's fever has resolved, after which the treatment will switch to oral azithromycin.

Conditions

Enteric Fever

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Meropenem arm

For the standard care protocol, patients are initially treated with meropenem 1g intravenously every 8 hours. Once their condition stabilizes , treatment is transitioned to oral azithromycin. The transition involves administering a first dose of azithromycin 1g orally, followed by a daily dose of 500mg orally. Intravenous meropenem will continue until 24 hours after the patient's fever has resolved, after which the treatment will switch to oral azithromycin.

Group Type: ACTIVE_COMPARATOR

Meropenem Injection

Intervention Type: DRUG

Meropenem 1000 mg IV Q8H

Azithromycin arm

In the intervention group, patients begin with azithromycin 1g administered intravenously for the initial dose, followed by a daily dose of 500mg intravenously. When the patient's condition stabilizes, the treatment will transition to oral azithromycin, starting with a 1g oral dose and continuing with 500mg orally once daily. Intravenous azithromycin will be maintained until 24 hours after the patient's fever has resolved, after which the treatment will switch to oral azithromycin

Group Type: EXPERIMENTAL

Azithromycin

Intervention Type: DRUG

Azithromycin 1g IV loading dose then 500mg IV OD

Interventions

Azithromycin

Azithromycin 1g IV loading dose then 500mg IV OD

Intervention Type: DRUG

Meropenem Injection

Meropenem 1000 mg IV Q8H

Intervention Type: DRUG

Other Intervention Names

Experimental group

Eligibility Criteria

Inclusion Criteria

• Participants will enrolled on following criteria

• Voluntarily sign the written informed consent
• Patient's of age 1-70 years with clinically suspected on physician decision or XDR enteric fever confirmed by blood culture and sensitivity tests.
• Married females with negative pregnancy test.
• No history of cardiac issues with ECG abnormalities, cholestatic jaundice/hepatic dysfunction associated with prior azithromycin use.
• Patients having no hypersensitivity (skin rashes, anaphylaxis) to azithromycin and meropenem
• Patients on concomitant medication, having no drug-drug interaction with meropenem and azithromycin will be included in study.

Exclusion Criteria

• Participants will excluded on following criteria

• Pregnant, lactating women or women of childbearing age with positive pregnancy test at baseline.
• Patients with known hypersensitivity (skin rashes, anaphylaxis) to azithromycin, meropenem, or any other macrolide or carbapenem antibiotics.
• Blood culture and sensitivity tests reported positive culture with MDR S. typhi (non-susceptibility to at least one agent in three or more antimicrobial categories,) o
• Patients with history of cardiac disorder with ECG abnormalities and history of cholestatic jaundice/hepatic dysfunction associated with prior azithromycin use will be excluded.
• Patients on continuous medication, having drug-drug interaction with meropenem and azithromycin will be excluded.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Indus Hospital and Health Network

OTHER

Sponsor Role: lead

Responsible Party

Muhammad Hamid Hanif

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

muhammad hamid

Role: PRINCIPAL_INVESTIGATOR

Indus Hospital and Health Network

Locations

Indus Hospital & Health Network - Mian Campus

Karachi, Sindh, Pakistan

Site Status: RECRUITING

Countries

Pakistan

Central Contacts

muhammad hamid, PharmD

Role: CONTACT

hamidryk155@gmail.com

+923017697904

Facility Contacts

muhammad hamid, PharmD

Role: primary

muhammad.hamid@tih.org.pk

03017697904 ext. 2529

Other Identifiers

IHHN_IRB_2024_10_010

Identifier Type: -

Identifier Source: org_study_id