Antibiotics for Children With Severe Diarrhoea (ABCD)

World Health Organization (WHO)

Status and phase: Completed; Phase 3

Conditions: Diarrhea

Treatments: Drug: Azithromycin; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT03130114

ERC.0002722

Details and patient eligibility

About

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.

Enrollment: 8,268 patients

Sex: All

Ages: 2 to 23 months old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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8,268 participants in 2 patient groups, including a placebo group

Control

Placebo Comparator group

Description:

Placebo mixture, 0.25 ml / kg / day

Treatment:

Other: Placebo

Azithromycin

Experimental group

Description:

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

Treatment:

Drug: Azithromycin