Enteric FeverPhase 4NCT07314281
Meropenem vs Azithromycin Efficacy in Case XDR Enteric Fever
A Phase 4 study testing Azithromycin and Meropenem Injection in people with Enteric Fever, run by Indus Hospital and Health Network at 1 site in Pakistan.
Trial 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… Read more about this study
- Who is it for?
- Ages 1 year to 70 years
- Conditions the study is for
- Enteric Fever
- What is being tested?
- Azithromycin and Meropenem Injection
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 sitePakistan
- Study dates
- 22 Apr 2025to 15 Jan 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Pakistan1 site, 1 recruiting
- Recruiting
Indus Hospital & Health Network - Mian Campus
Karachi, Sindh
muhammad hamid, PharmD, 03017697904 ext. 2529, muhammad.hamid@tih.org.pk
About this study
Official title: "Comparing Efficacy of Intravenous Azithromycin and Meropenem for Extensively Drug-Resistant Enteric Fever: A Randomized Controlled Trial" (Pilot Study)
- Primary Objective:
- To evaluate the efficacy of intravenous azithromycin compared with meropenem in the treatment of extensively drug-resistant (XDR) enteric fever.
- 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.
- Exploratory Objectives:
- To evaluate the drug resistance against intravenous azithromycin versus in treating XDR enteric fever.
Read the 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
- Being tested
- Azithromycin, Meropenem Injection
- Medical subject headings
- Typhoid Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzithromycinDrug
Also called Experimental group
Azithromycin 1g IV loading dose then 500mg IV OD
Meropenem InjectionDrug
Meropenem 1000 mg IV Q8H
| Study group | Role | What they receive |
|---|---|---|
| Meropenem arm | Active comparator | 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. Receives: Drug: Meropenem Injection |
| Azithromycin arm | Experimental | 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 Receives: Drug: Azithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fever defervescence
Proportion of participants with fever defervescence of temperature 37 ℃ at Mid-treatment outcome (Day 7). Temperature will be monitored and documented in degrees centigrade (°C)
Measured: Mid-treatment outcome (Day 7)
Salmonella Typhi eradication
Proportion of participants with Salmonella Typhi eradication in Blood culture test on day 3. After start of intervention, a clearance of blood culture will be monitor at day 3. if Salmonella Typhi in blood culture of day 3 will not eradicate, a second blood culture will be done on Day 7.
Measured: Mid-treatment outcome (Day 7)
Secondary outcomes (4)
Hospital Admission Days
Mean hospital length of stay (in days) will be compared between groups to evaluate differences in duration of hospitalization
Measured: End-of-treatment outcome (Day 14)
Cumulative Treatment Duration
Average total treatment duration, expressed in number of days, will be compared across groups to assess differences in cumulative therapy requirements
Measured: End-of-treatment outcome (Day 14)
Adverse Events Monitoring
Adverse events will be monitored throughout the study period, including abnormal clinical findings such as rash, pruritus, flushing, or angioedema of the face or extremities. Laboratory assessments (ECG and liver function tests) will be performed on Mid-treatment outcome (Day 7) to check any ECG changes and hepatotoxicity. Vital signs-including body temperature (°C), blood pressure (mmHg), and heart rate (beats/min) will be recorded daily from baseline (Day 1) to day of discharge from hospital.
Measured: Mid-treatment outcome (Day 7)
Antimicrobial Resistance and Cost of treatment
Antimicrobial resistance will be assessed by monitoring any changes in the susceptibility pattern of Salmonella Typhi isolates during the study period. The direct cost of treatment will be calculated in Pakistani Rupees (PKR), based on the total cost of vials utilized throughout the treatment course, and will be compared between study groups to evaluate overall cost-effectiveness.
Measured: End-of-treatment outcome (Day 14)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2026
- Study start22 Apr 2025
- Primary completion15 Jan 2027 (estimated)
- Study completion15 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Enteric FeverStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized, controlled, parallel open-label pilot study
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Indus Hospital and Health Network
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Muhammad Hamid Hanif, Indus Hospital and Health Network
- Investigators
- muhammad hamid, Principal investigator, Indus Hospital and Health Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07314281
- Sponsor's protocol ID
- IHHN_IRB_2024_10_010
- Status last verified
- May 2026
- First submitted
- 17 Sep 2025
- Last updated
- 8 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: will be shared till December 2025
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- "Comparing Efficacy of Intravenous Azithromycin and Meropenem for Extensively Drug-Resistant Enteric Fever: A Randomized Controlled Trial" (Pilot Study)
- ClinicalTrials.gov ID
- NCT07314281
- Acronym / sponsor ID
- IHHN_IRB_2024_10_010
- Conditions
- Enteric Fever
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Indus Hospital and Health NetworkUniversity, hospital or other
- Study start
- 22 Apr 2025 (actual)
- Primary completion
- 15 Jan 2027 (estimated)
- Study completion
- 15 Jan 2027 (estimated)
- First posted
- 2 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- Primary Objective:
- To evaluate the efficacy of intravenous azithromycin compared with meropenem in the treatment of extensively drug-resistant (XDR) enteric fever.
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- randomized, controlled, parallel open-label pilot study
| Arm | Type | Receives |
|---|---|---|
| Meropenem arm | Active comparator | Drug: Meropenem InjectionFor 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. |
| Azithromycin arm | Experimental | Drug: AzithromycinIn 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 |
Who may qualify
- Ages
- 1 year to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Participants will enrolled on following criteria
Key exclusion criteria (6 listed)
- Participants will excluded on following criteria
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzithromycinAlso: Experimental groupAzithromycin 1g IV loading dose then 500mg IV OD | Drug | Azithromycin arm |
| Meropenem InjectionMeropenem 1000 mg IV Q8H | Drug | Meropenem arm |
Primary outcome
Fever defervescence
Time frame: Mid-treatment outcome (Day 7)
Proportion of participants with fever defervescence of temperature 37 ℃ at Mid-treatment outcome (Day 7). Temperature will be monitored and documented in degrees centigrade (°C)
Salmonella Typhi eradication
Time frame: Mid-treatment outcome (Day 7)
Proportion of participants with Salmonella Typhi eradication in Blood culture test on day 3. After start of intervention, a clearance of blood culture will be monitor at day 3. if Salmonella Typhi in blood culture of day 3 will not eradicate, a second blood culture will be done on Day 7.
4 secondary outcomes
Hospital Admission Days
Time frame: End-of-treatment outcome (Day 14)
Cumulative Treatment Duration
Time frame: End-of-treatment outcome (Day 14)
Adverse Events Monitoring
Time frame: Mid-treatment outcome (Day 7)
Antimicrobial Resistance and Cost of treatment
Time frame: End-of-treatment outcome (Day 14)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2026.
- Individual participant dataSharing planned: No. will be shared till December 2025
Related trials for Enteric Fever
Active, not recruitingPhase 2
GOALIE: Intramuscular vs. Enteral Penicillin Prophylaxis to Prevent Progression of Latent RHD Trial
Rheumatic Heart Disease
RecruitingPhase 4
Opportunistic Pneumococcal Immunisation Trial in MALnutrition
Severe Acute Malnutrition in Childhood, Pneumococcal Disease
Active, not recruitingPhase 3
Clinical Efficacy of Typhoid Conjugate Vaccine (Vi-TCV) Among Children Age 9 Months Through 12 Years in Blantyre, Malawi
Typhoid
RecruitingPhase 4
CVD 38000: Study of Responses to Vaccination With Typhoid and/or Cholera
Typhoid and/or Cholera Vaccination
Not yet recruiting
COMPARISON OF SINGLE VERSUS COMBINATION DRUG THERAPY IN EXTENSIVELY DRUG RESISTANT SALMONELLA TYPHI IN TERMS OF TIME TO DEFERVESCENCE
Typhoid Fever
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
muhammad hamid principal investigator
Indus Hospital and Health Network
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Azithromycin and Meropenem Injection in people with Enteric Fever, run by Indus Hospital and Health Network at 1 site in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact muhammad hamid, PharmD (+923017697904, hamidryk155@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fever defervescence (time frame: Mid-treatment outcome (Day 7)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2026.