Dysentery, ShigellaPhase 4CIPAZNCT03854929
Ciprofloxacin Versus Azithromycin for Children Hospitalised With Dysentery
A Phase 4 study testing Ciprofloxacin and Azithromycin in people with Dysentery, Shigella and Shigellosis, run by Oxford University Clinical Research Unit, Vietnam at 1 site in Vietnam.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 60 months
- Conditions the study is for
- Dysentery, Shigella, Shigellosis, Diarrhea
- What is being tested?
- Ciprofloxacin and Azithromycin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 364 participants
- Where
- 1 siteVietnam
- Study dates
- 11 Dec 2019to 12 Jul 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 6 to 60 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Dysentery, Shigella, Shigellosis, Diarrhea
- Being tested
- Ciprofloxacin, Azithromycin
- Keywords
- Azithromycin, Ciprofloxacin, Children, Dysentery, Vietnam
- Medical subject headings
- Dysentery, Bacillary, Diarrhea, Dysentery
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CiprofloxacinDrug
Fluoroquinolone, ATC code: J01MA02
DNA-gyrase and topoisomerase IV inhibitor
AzithromycinDrug
Macrolide, ATC code: J01FA10
Binds to ribosomal 50S sub-unit inhibiting translocation of peptides thereby suppressing bacterial protein synthesis.
| Study group | Role | What they receive |
|---|---|---|
| Ciprofloxacin | Active comparator | 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. Receives: Drug: Ciprofloxacin |
| Azithromycin | Experimental | 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 Receives: Drug: Azithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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))
Measured: after 120 hours of start of either treatment.
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.
Measured: after 72 hours of start of either treatment.
Secondary outcomes (5)
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.
Measured: 120 hours of start of either treatment.
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.
Measured: 120 hours of start of either treatment.
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).
Measured: at enrolment, day 7th (+3 days) and day 28th (+3 days)
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.
Measured: at enrolment, during 31 days after enrolment
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)
Measured: at enrolment, day 7th (+3 days) and day 28th (+3 days).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2019
- Study start11 Dec 2019
- Primary completion6 Feb 2021
- Study completion12 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Dysentery, ShigellaStudies 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
- 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)
- Enrolment
- 364 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oxford University Clinical Research Unit, Vietnam
- Sponsor type
- University, hospital or other
- Collaborators
- Number 2 Children's Hospital, Ho Chi Minh City, University of Liverpool
- Responsible party
- Sponsor
- Investigators
- Stephen Stephen, Professor, Principal investigator, Oxford University Clinical Research Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03854929
- Sponsor's protocol ID
- 26EN
- Acronym
- CIPAZ
- Status last verified
- Jun 2023
- First submitted
- 21 Feb 2019
- Last updated
- 7 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03854929
- Acronym / sponsor ID
- CIPAZ / 26EN
- Conditions
- Dysentery, Shigella, Shigellosis, Diarrhea
- Keywords
- Azithromycin, Ciprofloxacin, Children, Dysentery, Vietnam
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 364 participants (actual)
- Lead sponsor
- Oxford University Clinical Research Unit, VietnamUniversity, hospital or other
- Collaborators
- Number 2 Children's Hospital, Ho Chi Minh City, University of Liverpool
- Study start
- 11 Dec 2019 (actual)
- Primary completion
- 6 Feb 2021 (actual)
- Study completion
- 12 Jul 2022 (actual)
- First posted
- 26 Feb 2019 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Ciprofloxacin | Active comparator | Drug: CiprofloxacinEach 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. |
| Azithromycin | Experimental | Drug: AzithromycinEach 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 |
Who may qualify
- Ages
- 6 to 60 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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:
- 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.
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 |
|---|---|---|
| CiprofloxacinFluoroquinolone, ATC code: J01MA02 DNA-gyrase and topoisomerase IV inhibitor | Drug | Ciprofloxacin |
| AzithromycinMacrolide, ATC code: J01FA10 Binds to ribosomal 50S sub-unit inhibiting translocation of peptides thereby suppressing bacterial protein synthesis. | Drug | Azithromycin |
Primary outcome
Assess the Clinical treatment failure between treatment groups.
Time frame: after 120 hours of start of either treatment.
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.
Time frame: after 72 hours of start of either treatment.
The microbiological treatment failure is assessed by positive PCR stool with original pathogen after day 3 of treatment.
5 secondary outcomes
Measure differences in symptom duration between treatment groups by stratifying stool PCR.
Time frame: 120 hours of start of either treatment.
Measure differences in symptom duration between treatment groups by stratifying stool culture.
Time frame: 120 hours of start of either treatment.
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 frame: at enrolment, day 7th (+3 days) and day 28th (+3 days)
Assess the rates of adverse events associated with exposure to the antimicrobial agents used.
Time frame: at enrolment, during 31 days after enrolment
Assess the effects of antimicrobial exposure on the host microbiome, including diversity and abundance of specific bacterial species in stool.
Time frame: at enrolment, day 7th (+3 days) and day 28th (+3 days).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2023.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
Stephen Stephen, Professor principal investigator
Oxford University Clinical Research Unit
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 Ciprofloxacin and Azithromycin in people with Dysentery, Shigella and Shigellosis, run by Oxford University Clinical Research Unit, Vietnam at 1 site in Vietnam.
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 5 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: finished, as of the sponsor's last update on 7 Jun 2023. 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 Vietnam. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess the Clinical treatment failure between treatment groups. (time frame: after 120 hours of start of either treatment.). 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 7 Jun 2023.