Meropenem vs Azithromycin Efficacy in Case XDR Enteric Fever

Indus Hospital and Health Network

Status and phase: Enrolling; Phase 4

Conditions: Enteric Fever

Treatments: Drug: Azithromycin; Drug: Meropenem Injection

Study type: Interventional

Funder types: Other

Identifiers

NCT07314281

IHHN_IRB_2024_10_010

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 1 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 2 patient groups

Meropenem arm

Active Comparator group

Description:

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.

Treatment:

Drug: Meropenem Injection

Azithromycin arm

Experimental group

Description:

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

Treatment:

Drug: Azithromycin