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Ciprofloxacin Versus Azithromycin for Children Hospitalised With Dysentery (CIPAZ)

Primary Purpose

Dysentery, Shigella, Shigellosis, Diarrhea

Status

Completed

Phase

Phase 4

Locations

Vietnam

Study Type

Interventional

Intervention

Ciprofloxacin

Azithromycin

About this trial

This is an interventional treatment trial for Dysentery, Shigella focused on measuring Azithromycin, Ciprofloxacin, Children, Dysentery, Vietnam

Eligibility Criteria

6 Months - 60 Months (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female aged 6 months to 60 months at time of hospital presentation.
Have symptoms and/or signs of dysentery, specifically passing stools containing mucus and/or blood with/without abdominal pain, tenesmus or fever (≥37.8˚C).
Be eligible for treatment with oral medication in the opinion of the admitting physician (i.e. no clinical requirement for parenteral treatment on admission).
Be within 72 hours of the onset of signs/symptoms.
Have a parent/guardian present at admission who can provide written informed consent.

Exclusion Criteria:

Those known to have specific medical (patients with known prolongation of the QT interval, congenital long QT syndrome)/surgical conditions which may affect disease severity/presentation or response to treatment (e.g. affecting antimicrobial absorption), including:
1. gastrointestinal abnormalities, including short bowel syndrome, chronic (inflammatory or irritable) bowel disease.
2. inherited or acquired immune system deficiency rendering the patient immunocompromised, including chronic/long-term steroid treatment or other immunosuppressive treatment
Presentation with severe infection requiring parenteral antimicrobial treatment, including shock jaundice, extensive gastrointestinal bleeding, convulsion , drowsiness or coma, reduced or less movement when stimulated, tachypnea > 60 times per minute, grunting, chest retraction, refuse to suck.
Known hypersensitivity to any of the trial drugs (CIP or AZI).
Coexisting infection requiring other or additional antimicrobials to be prescribed/ administered.

Sites / Locations

Children's Hospital 2

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Ciprofloxacin

Azithromycin

Arm Description

Each sachet CIPROFLOXACIN of 3g powder contains: 250mg Ciprofloxacin HCl, dissolved in water, dosed to 15mg/kg body weight /twice daily (apart 12 hours)/ 3 days.

Each sachet AZICINE of 1.5 g powder contains: 250mg of Azithromycin dihydrate, dissolved in warm water, dosed to 10mg/kg body weight /daily/ 3 days

Outcomes

Primary Outcome Measures

Assess the Clinical treatment failure between treatment groups.

Clinical treatment failure including: fever ≥38.0°C or the persistence of signs or symptoms of the infection (vomiting, abdominal pain, passing loose stools more than 3 times per 24 hours ( with blood and mucus, blood or mucus, without both))

Assess the microbiological treatment failure between treatment groups.

The microbiological treatment failure is assessed by positive PCR stool with original pathogen after day 3 of treatment.

Secondary Outcome Measures

Measure differences in symptom duration between treatment groups by stratifying stool PCR.

Compare the duration of symptom ( from the onset to disappear) between the two groups. The duration of symptom will be stratified by stool PCR.

Measure differences in symptom duration between treatment groups by stratifying stool culture.

Compare the duration of symptom ( from the onset to disappear) between the two groups. The duration of symptom will be stratified by stool culture.

Assess the time to resolution of objective markers of infection and inflammation, including cessation of culture- and PCR-confirmed Shigella shedding, normalization of blood total white cell count, C-reactive protein and stool lipocalin

Time to cessation of Shigella shedding in stool (PCR).

Assess the rates of adverse events associated with exposure to the antimicrobial agents used.

Adverse effects of antimicrobial treatment, including (i) life-threatening events, (ii) events requiring drug discontinuation, (iii) mild adverse events that require additional medication to be used but not resulting in drug discontinuation.

Assess the effects of antimicrobial exposure on the host microbiome, including diversity and abundance of specific bacterial species in stool.

The extend of intestinal microbial colonisation will be assessed by analyses of stool sample collected at enrolment, day 7th (+3 days) and day 28th (+3 days)

Full Information

NCT ID

NCT03854929

First Posted

February 21, 2019

Last Updated

June 5, 2023

Sponsor

Oxford University Clinical Research Unit, Vietnam

Collaborators

Number 2 Children's Hospital, Ho Chi Minh City, University of Liverpool

1. Study Identification

Unique Protocol Identification Number

NCT03854929

Brief Title

Ciprofloxacin Versus Azithromycin for Children Hospitalised With Dysentery

Acronym

CIPAZ

Official Title

An Open Label Randomised Controlled Trial of Azithromycin Versus Ciprofloxacin for the Treatment of Children Hospitalised With Dysentery in Ho Chi Minh City, Vietnam

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Completed

Study Start Date

December 11, 2019 (Actual)

Primary Completion Date

February 6, 2021 (Actual)

Study Completion Date

July 12, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Oxford University Clinical Research Unit, Vietnam

Collaborators

Number 2 Children's Hospital, Ho Chi Minh City, University of Liverpool

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to assess the efficacy of 3 days of azithromycin (AZI) compared to 3 days of ciprofloxacin (CIP) (standard-of-care) for the treatment of children hospitalised with dysentery in Ho Chi Minh City.

Detailed Description

Antimicrobial resistance is a well-established international healthcare crisis and children with diarrhoeal infections represent a significant proportion of the global infectious disease burden. With the increasing rates of antimicrobial resistance observed in the organisms associated with children presenting with dysentery in Vietnam and the investigator's capacity to demonstrate international transmission events, new data regarding alternative treatment options such as azithromycin, in particular for the new highly-antimicrobial resistant S. sonnei, are urgently needed. The study team will perform a phase IV open label randomised controlled trial to compare the efficacy of AZI to CIP (standard-of-care) for the treatment of children hospitalised with dysentery in Ho Chi Minh City, Vietnam. Children aged 6 to 60 months presenting to the participating hospital with symptoms/signs of dysentery (diarrhoea with blood and/or mucus accompanied by 1 or more of: fever ≥37.8°C, abdominal pain and /or tenesmus) within the previous 72 hours will be enrolled to the study. After enrolment, participants will be managed according to WHO and local algorithms for children with bloody diarrhoea. In addition, after providing a stool sample, children will be randomly allocated to receive CIP 15mg/kg body weight/ twice daily or AZI 10mg/kg body weight/ daily for 3 days. After enrolment, children will be reviewed for clinical and microbiological response to treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Dysentery, Shigella, Shigellosis, Diarrhea

Keywords

Azithromycin, Ciprofloxacin, Children, Dysentery, Vietnam

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

Randomization will be 1:1 to either AZI or CIP. Block randomization with stratification by hospital of enrolment, and variable block sizes of 4 and 6, respectively, will be used to assign subjects to treatment. The randomization list will be generated according to standard operating procedures without our organization. In brief, the Research Biostatistician (RB) will generate a randomization list using an in-house statistical code and transfer it to the central Study Pharmacist (SP). The SP will change the random seed to blind the RB and then run the code to prepare the final randomization list for treatment preparation. The randomization list will be saved and stored on a secure server. After enrolment, children will be randomly allocated to one of two treatment arms: in one arm, children will be treated with the current standard of care, oral CIP 15mg/kg BW /twice daily for 3 days, while those in the other arm will receive oral AZI 10mg/kg BW/daily for 3 days.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

364 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ciprofloxacin

Arm Type

Active Comparator

Arm Description

Each sachet CIPROFLOXACIN of 3g powder contains: 250mg Ciprofloxacin HCl, dissolved in water, dosed to 15mg/kg body weight /twice daily (apart 12 hours)/ 3 days.

Arm Title

Azithromycin

Arm Type

Experimental

Arm Description

Each sachet AZICINE of 1.5 g powder contains: 250mg of Azithromycin dihydrate, dissolved in warm water, dosed to 10mg/kg body weight /daily/ 3 days

Intervention Type

Drug

Intervention Name(s)

Ciprofloxacin

Intervention Description

Fluoroquinolone, ATC code: J01MA02 DNA-gyrase and topoisomerase IV inhibitor

Intervention Type

Drug

Intervention Name(s)

Azithromycin

Intervention Description

Macrolide, ATC code: J01FA10 Binds to ribosomal 50S sub-unit inhibiting translocation of peptides thereby suppressing bacterial protein synthesis.

Primary Outcome Measure Information:

Title

Assess the Clinical treatment failure between treatment groups.

Description

Time Frame

after 120 hours of start of either treatment.

Title

Assess the microbiological treatment failure between treatment groups.

Description

The microbiological treatment failure is assessed by positive PCR stool with original pathogen after day 3 of treatment.

Time Frame

after 72 hours of start of either treatment.

Secondary Outcome Measure Information:

Title

Measure differences in symptom duration between treatment groups by stratifying stool PCR.

Description

Compare the duration of symptom ( from the onset to disappear) between the two groups. The duration of symptom will be stratified by stool PCR.

Time Frame

120 hours of start of either treatment.

Title

Measure differences in symptom duration between treatment groups by stratifying stool culture.

Description

Compare the duration of symptom ( from the onset to disappear) between the two groups. The duration of symptom will be stratified by stool culture.

Time Frame

120 hours of start of either treatment.

Title

Description

Time to cessation of Shigella shedding in stool (PCR).

Time Frame

at enrolment, day 7th (+3 days) and day 28th (+3 days)

Title

Assess the rates of adverse events associated with exposure to the antimicrobial agents used.

Description

Time Frame

at enrolment, during 31 days after enrolment

Title

Assess the effects of antimicrobial exposure on the host microbiome, including diversity and abundance of specific bacterial species in stool.

Description

The extend of intestinal microbial colonisation will be assessed by analyses of stool sample collected at enrolment, day 7th (+3 days) and day 28th (+3 days)

Time Frame

at enrolment, day 7th (+3 days) and day 28th (+3 days).

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Months

Maximum Age & Unit of Time

60 Months

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female aged 6 months to 60 months at time of hospital presentation. Have symptoms and/or signs of dysentery, specifically passing stools containing mucus and/or blood with/without abdominal pain, tenesmus or fever (≥37.8˚C). Be eligible for treatment with oral medication in the opinion of the admitting physician (i.e. no clinical requirement for parenteral treatment on admission). Be within 72 hours of the onset of signs/symptoms. Have a parent/guardian present at admission who can provide written informed consent. Exclusion Criteria: Those known to have specific medical (patients with known prolongation of the QT interval, congenital long QT syndrome)/surgical conditions which may affect disease severity/presentation or response to treatment (e.g. affecting antimicrobial absorption), including: gastrointestinal abnormalities, including short bowel syndrome, chronic (inflammatory or irritable) bowel disease. inherited or acquired immune system deficiency rendering the patient immunocompromised, including chronic/long-term steroid treatment or other immunosuppressive treatment Presentation with severe infection requiring parenteral antimicrobial treatment, including shock jaundice, extensive gastrointestinal bleeding, convulsion , drowsiness or coma, reduced or less movement when stimulated, tachypnea > 60 times per minute, grunting, chest retraction, refuse to suck. Known hypersensitivity to any of the trial drugs (CIP or AZI). Coexisting infection requiring other or additional antimicrobials to be prescribed/ administered.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Stephen Stephen, Professor

Organizational Affiliation

Oxford University Clinical Research Unit

Official's Role

Principal Investigator

Facility Information:

Facility Name

Children's Hospital 2

City

Ho Chi Minh City

ZIP/Postal Code

70000

Country

Vietnam

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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Ciprofloxacin Versus Azithromycin for Children Hospitalised With Dysentery

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