Mortality Reduction After Oral Azithromycin Contingency: Mortality Study (MORDORIIMortY5)

MORDOR was a cluster-randomized placebo controlled trial that assessed the efficacy of mass azithromycin distributions for the prevention of childhood mortality. All communities were subsequently treated with mass azithromycin for one year. The present trial re-randomized communities to azithromycin or placebo for the fourth and fifth year of the study.

Study Overview

• Status: Completed
• Conditions: Childhood Mortality
• Intervention / Treatment: Drug: Azithromycin; Drug: Placebo

Detailed Description

Pre-trial treatments: in the original MORDOR trial, communities were randomized to 4 rounds of biannual mass distributions of either azithromycin or placebo (i.e, the first two years of the trial). All communities were subsequently treated with 2 rounds of biannual mass azithromycin (i.e., the fifth and sixth rounds, during the third year of the trial).

Present trial design: The present trial enrolls all communities previously enrolled in the Niger site of MORDOR, and re-randomizes communities to biannual mass distributions of either azithromycin or placebo (i.e., the seventh, eighth, ninth and tenth rounds of mass drug administration since randomization for the original MORDOR trial, occurring in the fourth and fifth year since randomization). This results in four patterns of community-based treatment: four years of azithromycin (AAAAA), three years of azithromycin followed by one year of placebo (AAAPP), two years of placebo followed by two years of azithromycin (PPAAA), and two years of placebo followed by one year of azithromycin and then one year of placebo (PPAPP). The primary outcome will be all-cause mortality in children aged 1-59 months,as determined by biannual census. The mortality rate following re-randomization (i.e., the seventh, eighth, ninth and tenth rounds of mass drug administration) will be compared between the two re-randomized groups.

• Study Type: Interventional
• Enrollment (Actual): 66228
• Phase: Phase 4

Contacts and Locations

Study Locations

• Niger
  • Niamey, Niger
    • The Carter Center
• United States
  • California
    • San Francisco, California, United States, 94143-0944
      • UCSF Proctor Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Communities- All communities eligible for MORDOR (NCT02047981)
• Individuals-All children aged 1-60 months (up to but not including the 5th birthday), as assessed via biannual census

Exclusion Criteria:

• Refusal of village chief (for village inclusion), or refusal of parent or guardian (for individual inclusion)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Azithro; Communities will receive four rounds of biannual mass azithromycin.	Drug: Azithromycin; Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months; Other Names: Zithromax
Placebo Comparator: Placebo; Communities will receive four rounds of biannual mass placebo.	Drug: Placebo; Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo suspension every 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause Mortality Rate in Children Aged 1-60 Months	as measured by presence on census and absence on sequential census due to death	24 months
Macrolide Resistance in Children Aged 1-60 Months	as measured by nasopharyngeal swabs	18 months
Normalized Macrolide Resistance in Children Aged 1-60 Months	as measured by rectal swabs. Fraction of macrolide resistance from stool specimens in children 1-60 months (core). For Niger, this includes RNA, DNA, and TAC-card methods (a binary outcome at the individual level).	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbial Composition of Stool	as measured by Meta-genomic Deep Sequencing	18 months
Campylobacter and Other Pathogenic Organisms in Stool	as measured by molecular techniques	18 months

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Bill and Melinda Gates Foundation; The Carter Center
• Investigators: Principal Investigator: Tom M Lietman, MD, UCSF Proctor Foundation; Study Director: Elodie Lebas, RN, UCSF Proctor Foundation

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2017
• Primary Completion (Actual): July 31, 2020
• Study Completion (Actual): July 31, 2020

Study Registration Dates

• First Submitted: November 7, 2017
• First Submitted That Met QC Criteria: November 7, 2017
• First Posted (Actual): November 9, 2017

Study Record Updates

• Last Update Posted (Actual): August 11, 2022
• Last Update Submitted That Met QC Criteria: July 15, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Infection; Azithromycin; Mass treatment; Childhood mortality
• Additional Relevant MeSH Terms: Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: 10-01036-Y4; OPP1032340-A (The Bill and Melinda Gates Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes