search
Back to results

Antibiotics for Children With Severe Diarrhoea (ABCD)

Primary Purpose

Diarrhea

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Azithromycin
Placebo
Sponsored by
World Health Organization
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diarrhea focused on measuring Mortality, Infant, Antibiotics, Linear Growth

Eligibility Criteria

2 Months - 23 Months (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Children aged 2 - 23 months, presenting to a designated health care facility at a participating study site with
  • Diarrhoea per caregiver perception and at least 3 loose or watery stools in the previous 24 hours,

  • Diarrhoea for less than 14 days prior to screening and with at least one of the following criteria at presentation:

    • Signs of some or severe dehydration as per WHO Pocket Book 2013
    • Moderately wasted as defined by a mid-upper arm circumference (MUAC) less than 125 mm (but greater than or equal to 115 mm) or a weight-for-length z-score (WLZ) greater than -3 standard deviations (SD) and less than or equal to -2 SD after rehydration during stabilization period or
    • Severely stunted (length-for-age z-score (LAZ) <-3 SD) and
  • Parent or guardian (caregiver) willing to allow household visits on day 2 and day 3 and willing to return to facility on day 90 and
  • Parent or guardian (caregiver) provides a consent for trial participation on behalf of the child, based on local standards

Exclusion Criteria:

  • Dysentery (gross blood in stool reported by caregiver or observed by healthcare worker (HCW)),
  • Suspected Vibrio cholerae infection (determined according to WHO guidelines or clinical suspicion),
  • Previously or currently enrolled in the ABCD study,
  • Concurrently enrolled in another interventional clinical trial,
  • Sibling or other child in the household enrolled in the ABCD study and currently taking study medication,
  • Signs of associated infections (pneumonia, severe febrile illness, meningitis, mastoiditis or acute ear infection) requiring antibiotic treatment,
  • Documented antibiotic use in the 14 days prior to screening (not including standard use of prophylactic antibiotics, i.e. co-trimoxazole use in human immunodeficiency virus (HIV) -exposed children),
  • Documented use of metronidazole within the last 14-days,
  • Known allergy or contraindication to azithromycin antibiotics,
  • Severe acute malnutrition (SAM) defined as weigh-for-length Z-score (WLZ) less than -3 SD, or MUAC less than 115 mm, or edema of both feet, or
  • Living too far from the enrolment health center to ensure adequate Directly Observed Therapy (DOT) on day 2 and day 3

Sites / Locations

  • Icddr,B
  • Centre for Public Health Kinetics
  • Kenya Medical Research Institute
  • Malawi-Liverpool-Wellcome Trust Clinical Research Programme
  • Centre pour le Développement des Vaccins (CVD-Mali)
  • Aga Khan University
  • Muhimbili University of Health and Allied Sciences

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Control

Azithromycin

Arm Description

Placebo mixture, 0.25 ml / kg / day

Azithromycin mixture (40 mg / ml), 0.25 ml / kg / day

Outcomes

Primary Outcome Measures

Mortality
Proportion of children dying per arm
Linear growth
Mean change in length-for-age Z-score per arm. The Z score will be arrived at from the WHO growth charts based on length in cms and age in months

Secondary Outcome Measures

Hospitalizations upto Day 90
Proportion of children with at least one hospitalization upto Day 90 per arm
Hospitalization or deaths upto day 90
Proportion of children with at least one hospitalization or death upto day 90 per arm
Early hospitalization or death (upto day 10)
Proportion of children with death or any hospitalization per arm (upto day 10)
Change in weight for length Z score
Mean change in weight-for-length Z-score per arm. The Z score will be arrived at from the WHO growth charts based on weight in kg and length in cm for each child
Change in weight for age Z score
Mean change in weight-for-age Z-score per arm. The Z score will be arrived at from the WHO growth charts based on weight in kg and age in months for each child
Change in Mid upper arm circumference
Mean change in MUAC (mm) per arm
Antimicrobial resistance in the community
Proportion of study participants per arm harbouring antibiotic resistant E. coli bacteria in their stools before any intervention
Antimicrobial resistance among the study participants (sub-group)
Proportion of study participants per arm harbouring antibiotic resistant S. pneumoniae bacteria in the naso-pharynx or E. coli bacteria in their stools
Antimicrobial resistance among close household child contacts (sub-group)
Proportion of siblings or other close household contacts (6-59 months old) per arm harbouring antibiotic resistant S. pneumoniae bacteria in the nasopharynx or E. coli bacteria in their stools

Full Information

First Posted
April 23, 2017
Last Updated
May 14, 2020
Sponsor
World Health Organization
Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh, Center for Public Health Kinetics, Kenya Medical Research Institute, University of Washington, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Liverpool, Centre pour le developpement des vaccines, Mali, University of Maryland, College Park, Aga Khan University, Muhimbili University of Health and Allied Sciences, Boston Children's Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT03130114
Brief Title
Antibiotics for Children With Severe Diarrhoea
Acronym
ABCD
Official Title
Antibiotics for Children With Severe Diarrhoea
Study Type
Interventional

2. Study Status

Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
May 13, 2017 (Actual)
Primary Completion Date
January 15, 2020 (Actual)
Study Completion Date
January 15, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
World Health Organization
Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh, Center for Public Health Kinetics, Kenya Medical Research Institute, University of Washington, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Liverpool, Centre pour le developpement des vaccines, Mali, University of Maryland, College Park, Aga Khan University, Muhimbili University of Health and Allied Sciences, Boston Children's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Although the current World Health Organization (WHO) recommended management package for acute diarrhoea (ORS, zinc and feeding advice) has contributed to significant reductions in diarrhoea associated mortality, over half a million children continue to die annually as a result of acute diarrhoeal episodes. In addition, rates of mortality in young children in the 90 days following an episode of acute diarrhoea appear at least as high as mortality that occurs during the acute episode. The long-term benefits of antibiotic administration may result from direct antimicrobial effects on pathogens or from other incompletely understood mechanisms including improved nutrition, alterations in immune tolerance or improved enteric function. Optimizing antibiotic treatment of acute diarrhoea episodes in very young children with severe disease may offer the opportunity to significantly reduce diarrhoea associated deaths in the 180 days following presentation for acute diarrhoea and may also improve growth. The investigators propose to evaluate the efficacy of an antibiotic (azithromycin) delivered in a specific, targeted fashion to young children (< 2 years of age) at high risk of diarrhoea associated mortality in a multi-site randomized, double-blind, placebo-controlled trial. The study will evaluate the ability of the intervention to reduce mortality within 180 days of the acute diarrhoeal episode, and improve nutritional status over the first 90 days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diarrhea
Keywords
Mortality, Infant, Antibiotics, Linear Growth

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Active drug (azithromycin) will be delivered as dry powder, in opaque glass bottles. Control children with receive placebo powder that will appear, smell, and taste similar to the active drug. All drug bottles will be coded with participant numbers only, so that no-one will know the contents of the bottle.
Allocation
Randomized
Enrollment
8268 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Placebo mixture, 0.25 ml / kg / day
Arm Title
Azithromycin
Arm Type
Experimental
Arm Description
Azithromycin mixture (40 mg / ml), 0.25 ml / kg / day
Intervention Type
Drug
Intervention Name(s)
Azithromycin
Intervention Description
Participants will receive rehydration, dietary counseling, one 20 mg tablet of zinc per day and 10 mg (0.35 ml) / kg of azithromycin syrup per day, for three days
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Participants will receive rehydration, dietary counseling, one 20 mg tablet of zinc per day and 0.25 ml / kg of placebo drug syrup per day, for three days
Primary Outcome Measure Information:
Title
Mortality
Description
Proportion of children dying per arm
Time Frame
180 days from enrolment
Title
Linear growth
Description
Mean change in length-for-age Z-score per arm. The Z score will be arrived at from the WHO growth charts based on length in cms and age in months
Time Frame
90 days from enrolment
Secondary Outcome Measure Information:
Title
Hospitalizations upto Day 90
Description
Proportion of children with at least one hospitalization upto Day 90 per arm
Time Frame
90 days
Title
Hospitalization or deaths upto day 90
Description
Proportion of children with at least one hospitalization or death upto day 90 per arm
Time Frame
90 days
Title
Early hospitalization or death (upto day 10)
Description
Proportion of children with death or any hospitalization per arm (upto day 10)
Time Frame
10 days
Title
Change in weight for length Z score
Description
Mean change in weight-for-length Z-score per arm. The Z score will be arrived at from the WHO growth charts based on weight in kg and length in cm for each child
Time Frame
90 days
Title
Change in weight for age Z score
Description
Mean change in weight-for-age Z-score per arm. The Z score will be arrived at from the WHO growth charts based on weight in kg and age in months for each child
Time Frame
90 days
Title
Change in Mid upper arm circumference
Description
Mean change in MUAC (mm) per arm
Time Frame
90 days
Title
Antimicrobial resistance in the community
Description
Proportion of study participants per arm harbouring antibiotic resistant E. coli bacteria in their stools before any intervention
Time Frame
Baseline
Title
Antimicrobial resistance among the study participants (sub-group)
Description
Proportion of study participants per arm harbouring antibiotic resistant S. pneumoniae bacteria in the naso-pharynx or E. coli bacteria in their stools
Time Frame
At the end of intervention (90 days) and three months later (180 days)
Title
Antimicrobial resistance among close household child contacts (sub-group)
Description
Proportion of siblings or other close household contacts (6-59 months old) per arm harbouring antibiotic resistant S. pneumoniae bacteria in the nasopharynx or E. coli bacteria in their stools
Time Frame
At the end of intervention (90 days) and three months later (180 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Months
Maximum Age & Unit of Time
23 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Children aged 2 - 23 months, presenting to a designated health care facility at a participating study site with Diarrhoea per caregiver perception and at least 3 loose or watery stools in the previous 24 hours, Diarrhoea for less than 14 days prior to screening and with at least one of the following criteria at presentation: Signs of some or severe dehydration as per WHO Pocket Book 2013 Moderately wasted as defined by a mid-upper arm circumference (MUAC) less than 125 mm (but greater than or equal to 115 mm) or a weight-for-length z-score (WLZ) greater than -3 standard deviations (SD) and less than or equal to -2 SD after rehydration during stabilization period or Severely stunted (length-for-age z-score (LAZ) <-3 SD) and Parent or guardian (caregiver) willing to allow household visits on day 2 and day 3 and willing to return to facility on day 90 and Parent or guardian (caregiver) provides a consent for trial participation on behalf of the child, based on local standards Exclusion Criteria: Dysentery (gross blood in stool reported by caregiver or observed by healthcare worker (HCW)), Suspected Vibrio cholerae infection (determined according to WHO guidelines or clinical suspicion), Previously or currently enrolled in the ABCD study, Concurrently enrolled in another interventional clinical trial, Sibling or other child in the household enrolled in the ABCD study and currently taking study medication, Signs of associated infections (pneumonia, severe febrile illness, meningitis, mastoiditis or acute ear infection) requiring antibiotic treatment, Documented antibiotic use in the 14 days prior to screening (not including standard use of prophylactic antibiotics, i.e. co-trimoxazole use in human immunodeficiency virus (HIV) -exposed children), Documented use of metronidazole within the last 14-days, Known allergy or contraindication to azithromycin antibiotics, Severe acute malnutrition (SAM) defined as weigh-for-length Z-score (WLZ) less than -3 SD, or MUAC less than 115 mm, or edema of both feet, or Living too far from the enrolment health center to ensure adequate Directly Observed Therapy (DOT) on day 2 and day 3
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rajiv Bahl
Organizational Affiliation
World Health Organization
Official's Role
Study Director
Facility Information:
Facility Name
Icddr,B
City
Dhaka
Country
Bangladesh
Facility Name
Centre for Public Health Kinetics
City
New Delhi
Country
India
Facility Name
Kenya Medical Research Institute
City
Nairobi
Country
Kenya
Facility Name
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
City
Blantyre
Country
Malawi
Facility Name
Centre pour le Développement des Vaccins (CVD-Mali)
City
Bamako
Country
Mali
Facility Name
Aga Khan University
City
Karachi
Country
Pakistan
Facility Name
Muhimbili University of Health and Allied Sciences
City
Dar es Salaam
Country
Tanzania

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
The Principal investigators are currently discussing this between themselves and their research organizations. The plan is to make the data available as soon as possible.
Citations:
PubMed Identifier
34913980
Citation
Antibiotics for Children With Diarrhea (ABCD) Study Group; Ahmed T, Chisti MJ, Rahman MW, Alam T, Ahmed D, Parvin I, Kabir MF, Sazawal S, Dhingra P, Dutta A, Deb S, Chouhan A, Sharma AK, Jaiswal VK, Dhingra U, Walson JL, Singa BO, Pavlinac PB, McGrath CJ, Nyabinda C, Deichsel EL, Anyango M, Kariuki KM, Rwigi D, Tornberg-Belanger SN, Kotloff KL, Sow SO, Tapia MD, Haidara FC, Mehta A, Coulibaly F, Badji H, Permala-Booth J, Tennant SM, Malle D, Bar-Zeev N, Dube Q, Freyne B, Cunliffe N, Ndeketa L, Witte D, Ndamala C, Cornick J, Qamar FN, Yousafzai MT, Qureshi S, Shakoor S, Thobani R, Hotwani A, Kabir F, Mohammed J, Manji K, Duggan CP, Kisenge R, Sudfeld CR, Kibwana U, Somji S, Bakari M, Msemwa C, Samma A, Bahl R, De Costa A, Simon J, Ashorn P. Effect of 3 Days of Oral Azithromycin on Young Children With Acute Diarrhea in Low-Resource Settings: A Randomized Clinical Trial. JAMA Netw Open. 2021 Dec 1;4(12):e2136726. doi: 10.1001/jamanetworkopen.2021.36726.
Results Reference
derived
PubMed Identifier
31931848
Citation
ABCD study team. A double-blind placebo-controlled trial of azithromycin to reduce mortality and improve growth in high-risk young children with non-bloody diarrhoea in low resource settings: the Antibiotics for Children with Diarrhoea (ABCD) trial protocol. Trials. 2020 Jan 13;21(1):71. doi: 10.1186/s13063-019-3829-y.
Results Reference
derived

Learn more about this trial

Antibiotics for Children With Severe Diarrhoea

We'll reach out to this number within 24 hrs