Comparison of Two Drugs Regimen in Treatment of Complicated Typhoid Fever in Children ([XDRTYPHOID])
Primary Purpose
Typhoid Fever
Status
Completed
Phase
Phase 4
Locations
Pakistan
Study Type
Interventional
Intervention
Meropenem Injection
Azithromycin Powder
Sponsored by
About this trial
This is an interventional treatment trial for Typhoid Fever focused on measuring XDR TYPHOID FEVER
Eligibility Criteria
Inclusion Criteria:
Patients with extended drug resistant typhoid fever defined as culture proven typhoid fever caused by Salmonella Typhi or Para typhi resistant to Ampicillin, Chloramphenicol,Co trimoxazole,Quinolones and Ceftriaxone along with two or more of the following condition
- High grade fever spikes for more than three days
- Refusal to eat or drink
- Drowsy or Unconscious
- Convulsions
- Dehydration due to diarrhea or vomiting
- Abdominal distension with or without tenderness
- Bleeding diathesis like petechial rash, gum bleed, melena
- Jaundice or alanine transaminase more than twice of the normal range
- Thrombocytopenia less than fifty thousand
- Increase Prothrombin time and activated partial thromboplastin time
- Electrolyte imbalance like hyponatremia, hypernatremia, hypokalemia, hyperkalemia, metabolic acidosis
- Hypoglycemia
- Signs of shock like cold and mottled skin, feeble pulses, tachycardia, decreased blood pressure
Exclusion Criteria:
- Not given informed consent
- Children who need ventilator or two inotrope support
- Severe malnutrition/immunocompromised patient
Sites / Locations
- Ziauddin University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
meropenum and azithromycin group
meropenum group
Arm Description
inj meropenum 20mg/kg/dose I/v in 3 divided doses and syp azithromycin 20mg/kg/day in 2 divided doses.
inj meropenum 20mg/kg/dose I/v in 3 divided doses
Outcomes
Primary Outcome Measures
clinical clearance
improvement of the signs and symptoms as given in the operational definition
Secondary Outcome Measures
bacterial clearance
negative blood cultures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04154722
Brief Title
Comparison of Two Drugs Regimen in Treatment of Complicated Typhoid Fever in Children
Acronym
[XDRTYPHOID]
Official Title
Treatment of 21st Century Typhoid Fever in Children;Open Label Mono vs Combination Drug Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
June 20, 2019 (Actual)
Primary Completion Date
December 30, 2020 (Actual)
Study Completion Date
December 30, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ziauddin University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This study evaluates whether XDR Typhoid fever in children can be effectively treated with monotherapy (meropenum alone), or a combination (meropenum and azithromycin).
Detailed Description
Complicated XDR Enteric fever is a very serious systemic disease, caused by an extremely resistant mutant strain of Salmonella Typhi ( the H58 S. Typhi superbug,) that as the name suggests is resistant to not only the first but also the second tier drugs conventionally used for treatment of the same. And as such, warrants immediate antibiotic therapy, but in view of the extended antimicrobial resistance the treatment options are limited to only two effective drugs viz Carbepenem and Azithromycin, as per culture sensitivity.
So far, in the absence of universal standardized treatment protocols for XDR complicated typhoid fever in children, random use of either one or both in combination is the current practice.
However, keeping antibiotic stewardship in mind, it is imperative to ascertain whether meropenum alone is effective or should be combined with azithromycin in the treatment of this serious disease.
Our study therefore compares the efficacy of monotherapy with meropenum or combination with azithromycin based on clinical and microbiologic remission, shortened hospital stay and less chances of relapse in order to then formulate a standardized protocol to treat complicated XDR typhoid in children thus preventing yet further antimicrobial resistance.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Typhoid Fever
Keywords
XDR TYPHOID FEVER
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
126 (Actual)
8. Arms, Groups, and Interventions
Arm Title
meropenum and azithromycin group
Arm Type
Experimental
Arm Description
inj meropenum 20mg/kg/dose I/v in 3 divided doses and syp azithromycin 20mg/kg/day in 2 divided doses.
Arm Title
meropenum group
Arm Type
Active Comparator
Arm Description
inj meropenum 20mg/kg/dose I/v in 3 divided doses
Intervention Type
Drug
Intervention Name(s)
Meropenem Injection
Other Intervention Name(s)
meroneum, penro
Intervention Description
inj meropenum for 10 days
Intervention Type
Drug
Intervention Name(s)
Azithromycin Powder
Other Intervention Name(s)
azomax, zetro
Intervention Description
syp azithromycin for10days
Primary Outcome Measure Information:
Title
clinical clearance
Description
improvement of the signs and symptoms as given in the operational definition
Time Frame
10 days
Secondary Outcome Measure Information:
Title
bacterial clearance
Description
negative blood cultures
Time Frame
5 days
Other Pre-specified Outcome Measures:
Title
relapse of typhoid fever
Description
reappearance of the signs and symptoms of typhoid fever along with positive blood cultures
Time Frame
15 days after completing treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with extended drug resistant typhoid fever defined as culture proven typhoid fever caused by Salmonella Typhi or Para typhi resistant to Ampicillin, Chloramphenicol,Co trimoxazole,Quinolones and Ceftriaxone along with two or more of the following condition
High grade fever spikes for more than three days
Refusal to eat or drink
Drowsy or Unconscious
Convulsions
Dehydration due to diarrhea or vomiting
Abdominal distension with or without tenderness
Bleeding diathesis like petechial rash, gum bleed, melena
Jaundice or alanine transaminase more than twice of the normal range
Thrombocytopenia less than fifty thousand
Increase Prothrombin time and activated partial thromboplastin time
Electrolyte imbalance like hyponatremia, hypernatremia, hypokalemia, hyperkalemia, metabolic acidosis
Hypoglycemia
Signs of shock like cold and mottled skin, feeble pulses, tachycardia, decreased blood pressure
Exclusion Criteria:
Not given informed consent
Children who need ventilator or two inotrope support
Severe malnutrition/immunocompromised patient
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
farhana zafar, mbbs,fcps
Organizational Affiliation
ziauddin university north campus
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ziauddin University
City
Karachi
State/Province
Sindh
ZIP/Postal Code
75600
Country
Pakistan
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Comparison of Two Drugs Regimen in Treatment of Complicated Typhoid Fever in Children
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