NCT03130114

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
8,268

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started May 2017

Typical duration for phase_3

Geographic Reach
6 countries

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 23, 2017

Completed
3 days until next milestone

First Posted

Study publicly available on registry

April 26, 2017

Completed
17 days until next milestone

Study Start

First participant enrolled

May 13, 2017

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 15, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 15, 2020

Completed
Last Updated

May 19, 2020

Status Verified

May 1, 2020

Enrollment Period

2.7 years

First QC Date

April 23, 2017

Last Update Submit

May 14, 2020

Conditions

Diarrhea

Keywords

MortalityInfantAntibioticsLinear Growth

Outcome Measures

Primary Outcomes (2)

  • Mortality

    Proportion of children dying per arm

    180 days from enrolment

  • 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

    90 days from enrolment

Secondary Outcomes (9)

  • Hospitalizations upto Day 90

    90 days

  • Hospitalization or deaths upto day 90

    90 days

  • Early hospitalization or death (upto day 10)

    10 days

  • Change in weight for length Z score

    90 days

  • Change in weight for age Z score

    90 days

  • +4 more secondary outcomes

Study Arms (2)

Control

PLACEBO COMPARATOR

Placebo mixture, 0.25 ml / kg / day

Other: Placebo

Azithromycin

EXPERIMENTAL

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

Drug: Azithromycin

Interventions

AzithromycinDRUG

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

Azithromycin
PlaceboOTHER

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

Control

Eligibility Criteria

Age2 Months - 23 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Icddr,B

Dhaka, Bangladesh

Location

Centre for Public Health Kinetics

New Delhi, India

Location

Kenya Medical Research Institute

Nairobi, Kenya

Location

Malawi-Liverpool-Wellcome Trust Clinical Research Programme

Blantyre, Malawi

Location

Centre pour le Développement des Vaccins (CVD-Mali)

Bamako, Mali

Location

Aga Khan University

Karachi, Pakistan

Location

Muhimbili University of Health and Allied Sciences

Dar es Salaam, Tanzania

Location

Related Publications (4)

  • Somji S, Ashorn P, Manji K, Ahmed T, Chisti M, Dhingra U, Sazawal S, Singa B, Walson JL, Pavlinac P, Bar-Zeev N, Houpt E, Dube Q, Kotloff K, Sow S, Yousafzai MT, Qamar F, Bahl R, De Costa A, Simon J, Sudfeld CR, Duggan CP; ABCD Study Group. Clinical and nutritional correlates of bacterial diarrhoea aetiology in young children: a secondary cross-sectional analysis of the ABCD trial. BMJ Paediatr Open. 2024 Apr 11;8(1):e002448. doi: 10.1136/bmjpo-2023-002448.

    PMID: 38604769DERIVED

  • Pavlinac PB, Platts-Mills JA, Liu J, Atlas HE, Gratz J, Operario D, Rogawski McQuade ET, Ahmed D, Ahmed T, Alam T, Ashorn P, Badji H, Bahl R, Bar-Zeev N, Chisti MJ, Cornick J, Chauhan A, De Costa A, Deb S, Dhingra U, Dube Q, Duggan CP, Freyne B, Gumbi W, Hotwani A, Kabir M, Islam O, Kabir F, Kasumba I, Kibwana U, Kotloff KL, Khan SS, Maiden V, Manji K, Mehta A, Ndeketa L, Praharaj I, Qamar FN, Sazawal S, Simon J, Singa BO, Somji S, Sow SO, Tapia MD, Tigoi C, Toure A, Walson JL, Yousafzai MT, Houpt ER; AntiBiotics for Children with severe Diarrhea (ABCD) Study Group. Azithromycin for Bacterial Watery Diarrhea: A Reanalysis of the AntiBiotics for Children With Severe Diarrhea (ABCD) Trial Incorporating Molecular Diagnostics. J Infect Dis. 2024 Apr 12;229(4):988-998. doi: 10.1093/infdis/jiad252.

    PMID: 37405406DERIVED

  • 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.

    PMID: 34913980DERIVED

  • 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.

    PMID: 31931848DERIVED

MeSH Terms

Conditions

Diarrhea

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Signs and Symptoms, DigestiveSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

ErythromycinMacrolidesPolyketidesLactonesOrganic Chemicals

Study Officials

  • Rajiv Bahl

    World Health Organization

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
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.
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Scientist

Study Record Dates

First Submitted

April 23, 2017

First Posted

April 26, 2017

Study Start

May 13, 2017

Primary Completion

January 15, 2020

Study Completion

January 15, 2020

Last Updated

May 19, 2020

Record last verified: 2020-05

Locations

PA(1)TA(1)IN(1)MA(1)KE(1)BA(1)