Mortality Reduction After Oral Azithromycin: Morbidity Study

NCT ID: NCT02048007

Last Updated: 2021-03-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

72000 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-11-30

Study Completion Date

2020-08-27

Brief Summary

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The long-term goal of this study is to more precisely define the role of mass azithromycin treatments as an intervention for reducing childhood morbidity and increasing growth, and for the potential selection of antibiotic resistance. The investigators propose a set of 3 cluster-randomized trials in Malawi, Niger, and Tanzania comparing communities randomized to oral azithromycin with those randomized to placebo. To assess the generalizability of the intervention, investigators will monitor for antibiotic resistance, which could potentially limit adoption of mass antibiotic treatments. The investigators will also assess several measures of infectious diseases. The investigators hypothesize that mass azithromycin treatments will reduce childhood morbidity and will be accompanied by an acceptable level of antibiotic resistance.

Detailed Description

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The investigators will assess childhood infectious disease morbidity and macrolide resistance over two years, comparing communities where children aged 1-60 months receive biannual oral azithromycin to communities where the children receive biannual oral placebo.

Randomization of Treatment Allocation. In each site, 30 communities within a contiguous area of 300,000 to 600,000 individuals will be randomized into the azithromycin or placebo arm. The investigators will use a simple random sample separately for each study site, but without stratification or block randomization within the site. These communities are being randomized from the same pool of communities eligible for a sister trial (Mortality Reduction After Oral Azithromycin (MORDOR) - Morbidity Study).

Specific Aims

Specific Aim 1: To assess whether macrolide resistance is greater in a population-based community sample of pre-school children, or in a clinic-based sample of ill pre-school children

Specific Aim 2: To assess whether biannual mass azithromycin treatments of pre-school children can eliminate ocular chlamydia in a hypoendemic area

Specific Aim 3: To assess the diversity of the microbiome of the nasopharynx, nares, conjunctiva, and gastrointestinal tract

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 infectious and nutritional morbidity 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

Morbidity monitoring:

Collect swabs (nasopharyngeal, nasal, conjunctival), blood samples, (thick/thin blood smears, hemoglobin, dried blood spots), and stool samples from 40 randomly selected children aged 1 month to 60 months per community; collect swabs (nasopharyngeal) from 40 randomly selected children aged 7-12 years per community.

Anthropometry for all children aged 1 to 60 months per community.

Collect nasopharyngeal swabs from all children aged 1-60 months who are seen at a local health clinic and have a respiratory complaint.

Group Type ACTIVE_COMPARATOR

Azithromycin

Intervention Type DRUG

Biannual mass oral azithromycin to children

Biannual mass oral placebo

Comparison of childhood infectious and nutritional morbidity 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

Collect swabs (nasopharyngeal, nasal, conjunctival), blood samples, (thick/thin blood smears, hemoglobin, dried blood spots), and stool samples from 40 randomly selected children aged 1 month to 60 months per community; collect swabs (nasopharyngeal) from 40 randomly selected children aged 7-12 years per community

Anthropometry for all children aged 1 to 60 months per community

Collect nasopharyngeal swabs from all children aged 1-60 months who are seen at a local health clinic and have a respiratory complaint

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Biannual mass oral placebo to children

Interventions

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Azithromycin

Biannual mass oral azithromycin to children

Intervention Type DRUG

Placebo

Biannual mass oral placebo to children

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 (Intervention):

\- Children-treated arms (all 3 sites): All children aged 1-60 months (up to but not including the 5th birthday), as assessed at the most recent biannual census

Individuals (Examination \& Sample Collection):

* All swabs, blood tests, and stool samples: A random sample of children aged 1-60 months (up to but not including the 5th birthday) based on the previous census
* Anthropometric measurements: All children aged 1-60 months (up to but not including the 5th birthday) will have anthropometric measurements assessed.
* Nasopharyngeal swabs in untreated children: A random sample of individuals aged 7 - 12 years (7th birthday up to but not including the 12th birthday), as assessed from the previous census
* Clinic-based nasopharyngeal swabs: All children aged 1-60 months (up to but not including the 5th birthday) who present to a local health clinic in the study area and report symptoms of a respiratory infection

Exclusion Criteria

Individuals:

* Pregnant women
* All those who are allergic to macrolides or azalides
* Refusal of village chief (for village inclusion), or refusal of parent or guardian (for individual inclusion)
Minimum Eligible Age

1 Month

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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Arzika AM, Abdou A, Maliki R, Lebas E, Cook C, Vanderschelden B, O'Brien KS, Cotter SY, Varnado NE, Callahan EK, Bailey RL, West SK, Rosenthal PJ, Porco TC, Lietman TM, Keenan JD; MORDOR-Niger Study Group. Biannual Mass Azithromycin Distributions for Preschool Children and Malaria Parasitemia: A Secondary Analysis of the MORDOR Cluster Randomized Trial. JAMA Netw Open. 2025 Aug 1;8(8):e2527148. doi: 10.1001/jamanetworkopen.2025.27148.

Reference Type DERIVED
PMID: 40824641 (View on PubMed)

Liu J, Brennhofer SA, Zhang J, Stroup S, Pholwat S, Arzika AM, Maliki R, Abdou A, Lebas E, O'Brien KS, Arnold BF, Keenan JD, Lietman TM, Platts-Mills JA, Rogawski McQuade ET, Houpt ER. Effect of biannual azithromycin on respiratory pathogens among symptomatic children: results from the randomised Macrolides Oraux pour Reduire les Deces avec un Oeil sur la Resistance (MORDOR) I trial. BMJ Glob Health. 2025 Feb 10;10(2):e016043. doi: 10.1136/bmjgh-2024-016043.

Reference Type DERIVED
PMID: 39929535 (View on PubMed)

Arzika AM, Mindo-Panusis D, Abdou A, Kadri B, Nassirou B, Maliki R, Alsoudi AF, Zhang T, Cotter SY, Lebas E, O'Brien KS, Callahan EK, Bailey RL, West SK, Goodhew EB, Martin DL, Arnold BF, Porco TC, Lietman TM, Keenan JD; Macrolides Oraux pour Reduire les Deces Avec un Oeil sur la Resistance (MORDOR)-Niger Study Group. Effect of Biannual Mass Azithromycin Distributions to Preschool-Aged Children on Trachoma Prevalence in Niger: A Cluster Randomized Clinical Trial. JAMA Netw Open. 2022 Aug 1;5(8):e2228244. doi: 10.1001/jamanetworkopen.2022.28244.

Reference Type DERIVED
PMID: 35997979 (View on PubMed)

Arzika AM, Maliki R, Goodhew EB, Rogier E, Priest JW, Lebas E, O'Brien KS, Le V, Oldenburg CE, Doan T, Porco TC, Keenan JD, Lietman TM, Martin DL, Arnold BF; MORDOR-Niger Study Group. Effect of biannual azithromycin distribution on antibody responses to malaria, bacterial, and protozoan pathogens in Niger. Nat Commun. 2022 Feb 21;13(1):976. doi: 10.1038/s41467-022-28565-5.

Reference Type DERIVED
PMID: 35190534 (View on PubMed)

Hart JD, Samikwa L, Meleke H, Burr SE, Cornick J, Kalua K, Bailey RL. Prevalence of nasopharyngeal Streptococcus pneumoniae carriage and resistance to macrolides in the setting of azithromycin mass drug administration: analysis from a cluster-randomised controlled trial in Malawi, 2015-17. Lancet Microbe. 2022 Feb;3(2):e142-e150. doi: 10.1016/S2666-5247(21)00279-2.

Reference Type DERIVED
PMID: 35156069 (View on PubMed)

Arzika AM, Maliki R, Ali MM, Alio MK, Abdou A, Cotter SY, Varnado NE, Lebas E, Cook C, Oldenburg CE, O'Brien KS, Callahan EK, Bailey RL, West SK, Porco TC, Lietman TM, Keenan JD; MORDOR-Niger Study Group. Effect of Mass Azithromycin Distributions on Childhood Growth in Niger: A Cluster-Randomized Trial. JAMA Netw Open. 2021 Dec 1;4(12):e2139351. doi: 10.1001/jamanetworkopen.2021.39351.

Reference Type DERIVED
PMID: 34967883 (View on PubMed)

Bloch EM, Mrango Z, Weaver J, Munoz B, Lietman TM, West SK. Causes of death after biannual azithromycin treatment: A community-level randomized clinical trial. PLoS One. 2021 Sep 24;16(9):e0250197. doi: 10.1371/journal.pone.0250197. eCollection 2021.

Reference Type DERIVED
PMID: 34559801 (View on PubMed)

Arzika AM, Maliki R, Boubacar N, Kane S, Cotter SY, Lebas E, Cook C, Bailey RL, West SK, Rosenthal PJ, Porco TC, Lietman TM, Keenan JD; MORDOR Study Group. Biannual mass azithromycin distributions and malaria parasitemia in pre-school children in Niger: A cluster-randomized, placebo-controlled trial. PLoS Med. 2019 Jun 25;16(6):e1002835. doi: 10.1371/journal.pmed.1002835. eCollection 2019 Jun.

Reference Type DERIVED
PMID: 31237871 (View on PubMed)

West SK, Bloch E, Weaver J, Munoz B, Mrango Z, Kasubi M, Lietman T, Coles C. Morbidity in a Longitudinal Cohort of Children Residing in Villages Randomized to Biannual Treatment With Azithromycin Versus Placebo. Clin Infect Dis. 2020 Feb 3;70(4):574-580. doi: 10.1093/cid/ciz269.

Reference Type DERIVED
PMID: 30950493 (View on PubMed)

Oldenburg CE, Arzika AM, Maliki R, Kane MS, Lebas E, Ray KJ, Cook C, Cotter SY, Zhou Z, West SK, Bailey R, Porco TC, Keenan JD, Lietman TM; MORDOR Study Group. Safety of azithromycin in infants under six months of age in Niger: A community randomized trial. PLoS Negl Trop Dis. 2018 Nov 12;12(11):e0006950. doi: 10.1371/journal.pntd.0006950. eCollection 2018 Nov.

Reference Type DERIVED
PMID: 30419040 (View on PubMed)

Doan T, Hinterwirth A, Arzika AM, Cotter SY, Ray KJ, O'Brien KS, Zhong L, Chow ED, Zhou Z, Cummings SL, Fry D, Oldenburg CE, Worden L, Porco TC, Keenan JD, Lietman TM. Mass Azithromycin Distribution and Community Microbiome: A Cluster-Randomized Trial. Open Forum Infect Dis. 2018 Jul 24;5(8):ofy182. doi: 10.1093/ofid/ofy182. eCollection 2018 Aug.

Reference Type DERIVED
PMID: 30151409 (View on PubMed)

Doan T, Arzika AM, Ray KJ, Cotter SY, Kim J, Maliki R, Zhong L, Zhou Z, Porco TC, Vanderschelden B, Keenan JD, Lietman TM. Gut Microbial Diversity in Antibiotic-Naive Children After Systemic Antibiotic Exposure: A Randomized Controlled Trial. Clin Infect Dis. 2017 May 1;64(9):1147-1153. doi: 10.1093/cid/cix141.

Reference Type DERIVED
PMID: 28402408 (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)

Other Identifiers

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OPP1032340-B

Identifier Type: -

Identifier Source: org_study_id

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