Mortality Reduction After Oral Azithromycin: Mortality Study

NCT ID: NCT02047981

Last Updated: 2022-11-08

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

190238 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-12-31

Study Completion Date

2018-09-30

Brief Summary

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Our long-term goal is to more precisely define the role of mass azithromycin treatments as an intervention for reducing childhood mortality. We propose a single multi-site (multi-country), cluster-randomized trial comparing communities randomized to oral azithromycin with those randomized to placebo. We hypothesize that mass azithromycin treatments will reduce childhood mortality.

Detailed Description

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We will assess childhood mortality over three years, comparing communities where children aged 1-60 months receive biannual oral azithromycin ("Azithromycin" arm) for two years, to communities where the children receive biannual oral placebo ("Control" arm) for two years. During the third year at the Niger site only, everyone will receive azithromycin.

This is a cluster-randomized trial; at each site, communities within a contiguous area of 300,000 to 600,000 individuals will be randomized to azithromycin or placebo using simple random sampling.

Niger contingency study: In the event that mass distributions of oral azithromycin are proven to reduce mortality in 1-60 month-old children, then we will treat all communities in Niger with mass azithromycin distributions to test whether the intervention continues to reduce childhood mortality after the initial 2 years of mass treatments.

Conditions

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Childhood Mortality

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Biannual mass oral azithromycin

Comparison of childhood mortality in communities randomized to azithromycin versus communities randomized to placebo.

Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months for 2 years.

In Niger during year 3, all communities will be offered azithroymcin.

Group Type ACTIVE_COMPARATOR

Azithromycin

Intervention Type DRUG

Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months for 2 years. In Niger during year 3, all communities will be offered azithroymcin.

Biannual mass oral placebo

Comparison of childhood mortality in communities randomized to azithromycin versus communities randomized to placebo.

Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo every 6 months for 2 years

In Niger during year 3, all communities will be offered azithroymcin.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo every 6 months for 2 years. In Niger during year 3, all communities will be offered azithroymcin.

Interventions

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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 for 2 years. In Niger during year 3, all communities will be offered azithroymcin.

Intervention Type DRUG

Placebo

Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo every 6 months for 2 years. In Niger during year 3, all communities will be offered azithroymcin.

Intervention Type DRUG

Other Intervention Names

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Zithromax

Eligibility Criteria

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Inclusion Criteria

Communities

* The community location in target district.
* The community leader consents to participation in the trial
* The community's estimated population is between 200-2,000 people.
* The community is not in an urban area.

Individuals - All children aged 1-60 months (up to but not including the 5th birthday), as assessed via biannual census.

Exclusion Criteria

Individuals

\- Refusal of village chief (for village inclusion), or refusal of parent or guardian (for individual inclusion)
Minimum Eligible Age

1 Month

Maximum Eligible Age

60 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Bill and Melinda Gates Foundation

OTHER

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role collaborator

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tom M Lietman, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Elodie J Lebas, RN

Role: STUDY_DIRECTOR

University of California, San Francisco

Locations

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UCSF Proctor Foundation

San Francisco, California, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

College of Medicine at the University of Malawi, Blantyre

Blantyre, , Malawi

Site Status

The Carter Center, Niger

Niamey, , Niger

Site Status

Kongwa Trachoma Project

Kongwa, , Tanzania

Site Status

London School of Hygiene & Tropical Medicine

London, , United Kingdom

Site Status

Countries

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United States Malawi Niger Tanzania United Kingdom

References

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Peterson B, Arzika AM, Amza A, Maliki R, Karamba AM, Moussa M, Kemago M, Liu Z, Houpt E, Liu J, Pholwat S, Doan T, Porco TC, Keenan JD, Lietman TM, O'Brien KS. Assessment of Spillover of Antimicrobial Resistance to Untreated Children 7-12 Years Old After Mass Drug Administration of Azithromycin for Child Survival in Niger: A Secondary Analysis of the MORDOR Cluster-Randomized Trial. Clin Infect Dis. 2024 Nov 22;79(5):1136-1143. doi: 10.1093/cid/ciae267.

Reference Type DERIVED
PMID: 38739754 (View on PubMed)

Arzika AM, Abdou A, Maliki R, Beido N, Kadri B, Harouna AN, Galo AN, Alio MK, Lebas E, Oldenburg CE, O'Brien KS, Chen C, Zhong L, Zhou Z, Yan D, Hinterwirth A, Keenan JD, Porco TC, Lietman TM, Doan T; MORDOR Study Group. Prolonged mass azithromycin distributions and macrolide resistance determinants among preschool children in Niger: A sub-study of a cluster-randomized trial (MORDOR). PLoS Med. 2024 May 6;21(5):e1004386. doi: 10.1371/journal.pmed.1004386. eCollection 2024 May.

Reference Type DERIVED
PMID: 38709718 (View on PubMed)

Chao DL, Arzika AM, Abdou A, Maliki R, Karamba A, Galo N, Beidi D, Harouna N, Abarchi M, Root E, Mishra A, Lebas E, Arnold BF, Oldenburg CE, Keenan JD, Lietman TM, O'Brien KS. Distance to Health Centers and Effectiveness of Azithromycin Mass Administration for Children in Niger: A Secondary Analysis of the MORDOR Cluster Randomized Trial. JAMA Netw Open. 2023 Dec 1;6(12):e2346840. doi: 10.1001/jamanetworkopen.2023.46840.

Reference Type DERIVED
PMID: 38100110 (View on PubMed)

Pickering H, Hart JD, Burr S, Stabler R, Maleta K, Kalua K, Bailey RL, Holland MJ. Impact of azithromycin mass drug administration on the antibiotic-resistant gut microbiome in children: a randomized, controlled trial. Gut Pathog. 2022 Jan 6;14(1):5. doi: 10.1186/s13099-021-00478-6.

Reference Type DERIVED
PMID: 34991704 (View on PubMed)

Arzika AM, Maliki R, Abdou A, Mankara AK, Harouna AN, Cook C, Hinterwirth A, Worden L, Zhong L, Chen C, Ruder K, Zhou Z, Lebas E, O'Brien KS, Oldenburg CE, Le V, Arnold BF, Porco TC, Keenan JD, Lietman TM, Doan T. Gut Resistome of Preschool Children After Prolonged Mass Azithromycin Distribution: A Cluster-randomized Trial. Clin Infect Dis. 2021 Oct 5;73(7):1292-1295. doi: 10.1093/cid/ciab485.

Reference Type DERIVED
PMID: 34037753 (View on PubMed)

Doan T, Worden L, Hinterwirth A, Arzika AM, Maliki R, Abdou A, Zhong L, Chen C, Cook C, Lebas E, O'Brien KS, Oldenburg CE, Chow ED, Porco TC, Lipsitch M, Keenan JD, Lietman TM. Macrolide and Nonmacrolide Resistance with Mass Azithromycin Distribution. N Engl J Med. 2020 Nov 12;383(20):1941-1950. doi: 10.1056/NEJMoa2002606.

Reference Type DERIVED
PMID: 33176084 (View on PubMed)

O'Brien KS, Arzika AM, Maliki R, Manzo F, Mamkara AK, Lebas E, Cook C, Bailey RL, West SK, Oldenburg CE, Porco TC, Arnold B, Keenan JD, Lietman TM; MORDOR Study Group. Biannual azithromycin distribution and child mortality among malnourished children: A subgroup analysis of the MORDOR cluster-randomized trial in Niger. PLoS Med. 2020 Sep 15;17(9):e1003285. doi: 10.1371/journal.pmed.1003285. eCollection 2020 Sep.

Reference Type DERIVED
PMID: 32931496 (View on PubMed)

Doan T, Hinterwirth A, Arzika AM, Worden L, Chen C, Zhong L, Oldenburg CE, Keenan JD, Lietman TM. Reduction of Coronavirus Burden With Mass Azithromycin Distribution. Clin Infect Dis. 2020 Nov 19;71(16):2282-2284. doi: 10.1093/cid/ciaa606.

Reference Type DERIVED
PMID: 32426812 (View on PubMed)

Keenan JD, Arzika AM, Maliki R, Elh Adamou S, Ibrahim F, Kiemago M, Galo NF, Lebas E, Cook C, Vanderschelden B, Bailey RL, West SK, Porco TC, Lietman TM; MORDOR-Niger Study Group. Cause-specific mortality of children younger than 5 years in communities receiving biannual mass azithromycin treatment in Niger: verbal autopsy results from a cluster-randomised controlled trial. Lancet Glob Health. 2020 Feb;8(2):e288-e295. doi: 10.1016/S2214-109X(19)30540-6.

Reference Type DERIVED
PMID: 31981558 (View on PubMed)

Bloch EM, Munoz B, Mrango Z, Weaver J, Mboera LEG, Lietman TM, Sullivan DJ Jr, West SK. The impact on malaria of biannual treatment with azithromycin in children age less than 5 years: a prospective study. Malar J. 2019 Aug 23;18(1):284. doi: 10.1186/s12936-019-2914-8.

Reference Type DERIVED
PMID: 31443654 (View on PubMed)

Doan T, Arzika AM, Hinterwirth A, Maliki R, Zhong L, Cummings S, Sarkar S, Chen C, Porco TC, Keenan JD, Lietman TM; MORDOR Study Group. Macrolide Resistance in MORDOR I - A Cluster-Randomized Trial in Niger. N Engl J Med. 2019 Jun 6;380(23):2271-2273. doi: 10.1056/NEJMc1901535. No abstract available.

Reference Type DERIVED
PMID: 31167060 (View on PubMed)

Keenan JD, Arzika AM, Maliki R, Boubacar N, Elh Adamou S, Moussa Ali M, Cook C, Lebas E, Lin Y, Ray KJ, O'Brien KS, Doan T, Oldenburg CE, Callahan EK, Emerson PM, Porco TC, Lietman TM. Longer-Term Assessment of Azithromycin for Reducing Childhood Mortality in Africa. N Engl J Med. 2019 Jun 6;380(23):2207-2214. doi: 10.1056/NEJMoa1817213.

Reference Type DERIVED
PMID: 31167050 (View on PubMed)

Porco TC, Hart J, Arzika AM, Weaver J, Kalua K, Mrango Z, Cotter SY, Stoller NE, O'Brien KS, Fry DM, Vanderschelden B, Oldenburg CE, West SK, Bailey RL, Keenan JD, Lietman TM; Macrolides Oraux pour Reduire les Deces avec un Oeil sur la Resistance (MORDOR) Study Group. Mass Oral Azithromycin for Childhood Mortality: Timing of Death After Distribution in the MORDOR Trial. Clin Infect Dis. 2019 May 30;68(12):2114-2116. doi: 10.1093/cid/ciy973.

Reference Type DERIVED
PMID: 30561577 (View on PubMed)

Keenan JD, Bailey RL, West SK, Arzika AM, Hart J, Weaver J, Kalua K, Mrango Z, Ray KJ, Cook C, Lebas E, O'Brien KS, Emerson PM, Porco TC, Lietman TM; MORDOR Study Group. Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa. N Engl J Med. 2018 Apr 26;378(17):1583-1592. doi: 10.1056/NEJMoa1715474.

Reference Type DERIVED
PMID: 29694816 (View on PubMed)

Porco TC, Stoller NE, Keenan JD, Bailey RL, Lietman TM. Public key cryptography for quality assurance in randomization for clinical trials. Contemp Clin Trials. 2015 May;42:167-8. doi: 10.1016/j.cct.2015.03.016. Epub 2015 Apr 7. No abstract available.

Reference Type DERIVED
PMID: 25858004 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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OPP1032340-A

Identifier Type: -

Identifier Source: org_study_id

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