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Completed

NCT Number: NCT03130114

Antibiotics for Children With Severe Diarrhoea

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.

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Key information

Conditions

Diarrhea Pathological Conditions, Signs and Symptoms Signs and Symptoms Signs and Symptoms, Digestive

Age range

2 month–23 month

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Icddr,B, Dhaka, Bangladesh

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Azithromycin

Drug

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

Placebo

Other

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 outcomes

  1. Mortality

    Time frame: 180 days from enrolment

    Proportion of children dying per arm

  2. Linear growth

    Time frame: 90 days from enrolment

    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 outcomes

  1. Hospitalizations upto Day 90

    Time frame: 90 days

    Proportion of children with at least one hospitalization upto Day 90 per arm

  2. Hospitalization or deaths upto day 90

    Time frame: 90 days

    Proportion of children with at least one hospitalization or death upto day 90 per arm

  3. Early hospitalization or death (upto day 10)

    Time frame: 10 days

    Proportion of children with death or any hospitalization per arm (upto day 10)

  4. Change in weight for length Z score

    Time frame: 90 days

    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

  5. Change in weight for age Z score

    Time frame: 90 days

    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

  6. Change in Mid upper arm circumference

    Time frame: 90 days

    Mean change in MUAC (mm) per arm

  7. Antimicrobial resistance in the community

    Time frame: Baseline

    Proportion of study participants per arm harbouring antibiotic resistant E. coli bacteria in their stools before any intervention

  8. Antimicrobial resistance among the study participants (sub-group)

    Time frame: At the end of intervention (90 days) and three months later (180 days)

    Proportion of study participants per arm harbouring antibiotic resistant S. pneumoniae bacteria in the naso-pharynx or E. coli bacteria in their stools

  9. Antimicrobial resistance among close household child contacts (sub-group)

    Time frame: At the end of intervention (90 days) and three months later (180 days)

    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

Sponsors and collaborators

Lead sponsor

World Health Organization

Other

Collaborators

  • Aga Khan University
  • Boston Children's Hospital
  • Center for Public Health Kinetics
  • Centre pour le developpement des vaccines, Mali
  • International Centre for Diarrhoeal Disease Research, Bangladesh
  • Kenya Medical Research Institute
  • Malawi-Liverpool-Wellcome Trust Clinical Research Programme
  • Muhimbili University of Health and Allied Sciences
  • University of Liverpool
  • University of Maryland, College Park
  • University of Washington

Registry information

Acronym: ABCD

Important dates

Study start
2017
Primary completion
2020
Study completion
2020
First posted
Apr 26, 2017
Registry last updated
May 19, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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