Ciprofloxacin Versus Azithromycin for Children Hospitalised With Dysentery

NCT03854929 | Completed Phase 4

• 1 other identifier: 26EN
• Study Type: interventional
• Target: 364
• Locations: 1 country
• Sites: 1

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.

Conditions

Dysentery, Shigella; Shigellosis; Diarrhea

Keywords

Azithromycin; Ciprofloxacin; Children; Dysentery; Vietnam

Outcome Measures

Primary Outcomes (2)

• 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))

  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.

  after 72 hours of start of either treatment.

Secondary Outcomes (5)

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

  120 hours of start of either treatment.

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

  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

  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.

  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.

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

Study Arms (2)

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.

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

Drug: Azithromycin

Interventions

Ciprofloxacin DRUG

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

Ciprofloxacin

Azithromycin DRUG

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

Azithromycin

Eligibility Criteria

• Age: 6 Months - 60 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Oxford University Clinical Research Unit, Vietnam: lead
• Number 2 Children's Hospital, Ho Chi Minh City: collaborator
• University of Liverpool: collaborator

Study Sites (1)

Children's Hospital 2

Ho Chi Minh City, 70000, Vietnam

Location

MeSH Terms

Conditions

Dysentery, Bacillary; Diarrhea; Dysentery

Interventions

Ciprofloxacin; Azithromycin

Condition Hierarchy (Ancestors)

Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Stephen Stephen, Professor

  Oxford University Clinical Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 21, 2019
• First Posted: February 26, 2019
• Study Start: December 11, 2019
• Primary Completion: February 6, 2021
• Study Completion: July 12, 2022
• Last Updated: June 7, 2023

Record last verified: 2023-06

Locations

VN (1)