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CompletedNCT02048007MORDORMorbUpdated Mar 17, 2021

Mortality Reduction After Oral Azithromycin: Morbidity Study

A Phase 4 interventional study of Azithromycin and Placebo in Childhood Mortality, sponsored by University of California, San Francisco. Completed at 6 sites in 5 countries. Open to participants aged 1 Month and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-03-17.

Sponsored by University of California, San Francisco · Phase 4, Interventional, and Treatment

From the registry’s dates

  • Primary completion was Aug 2020, 6 years 2 months ago, and no results have been posted to the registry.
Phase
Phase 4
Study type
Interventional
Enrollment
72,000
Allocation
Randomized
Ages
1 Month and older
Sex
All
01

Study summary

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.

Read the detailed description

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

02

Conditions studied

  • Childhood Mortality

Keywords

  • Childhood mortality
  • Azithromycin
  • Mass treatment
  • Infection
  • Bacterial infections
  • Trachoma
  • Chlamydia infections
  • Malaria
  • Diarrhea
  • Respiratory Infections
  • Antibiotic resistance
  • Verbal Autopsy
  • Microbiome
03

In context

Infections

2,093 studies on the registry are indexed under Infections; 364 are open to participants now.

This study's enrollment of 72,000 is above the median of 113 across 1,304 interventional studies indexed under Infections.

Browse Infections studies →

Lead sponsor

University of California, San Francisco is the lead sponsor of 2,169 studies on the registry; 372 are open to participants now.

Of its 267 completed or terminated interventional studies of FDA-regulated products, 202 (76%) have results posted.

Browse University of California, San Francisco studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
1 Month and older
Sexes eligible
All
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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)
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
72,000 participants (actual)

Study arms

  • Active comparator
    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.

    Drug: Azithromycin

  • Placebo comparator
    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

    Drug: Placebo

Interventions

  • DrugAzithromycin

    Biannual mass oral azithromycin to children

    Also known as: Zithromax

  • DrugPlacebo

    Biannual mass oral placebo to children

06

What researchers measure

Primary outcomes

  1. Presence of malaria parasites on thick blood smear or Rapid Diagnostic Test (RDT) in children 1-60 months

    MORDOR Malawi, Tanzania and Niger. Please note: Each outcome will be analyzed separately for each study site.

    Time frame: Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months

  2. Fraction of isolates of pneumococcus exhibiting macrolide resistance by nasopharyngeal swabs in children 1-60 months

    MORDOR Malawi, Tanzania and Niger. Please note: Each outcome will be analyzed separately for each study site.

    Time frame: Each site will report outcomes at 24 months; Niger will also report outcomes at 36 months

  3. Prevalence of macrolide resistance in the stool as determined by genetic determinants or phenotypic testing

    MORDOR Malawi, Tanzania and Niger. Please note: Each outcome will be analyzed separately for each study site.

    Time frame: Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months

  4. Fraction of conjunctival swabs yielding ocular chlamydia in children 1-60 months

    MORDOR Malawi and Niger. Please note: Each outcome will be analyzed separately for each study site.

    Time frame: 24 months

  5. Height over time in children aged 1-60 months

    MORDOR Malawi and Niger Please note: Each outcome will be analyzed separately in each of the two study sites.

    Time frame: Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months

  6. Weight for Height over time in children aged 1-60 months

    MORDOR Malawi and Niger Please note:Each outcome will be analyzed separately in each of the two study sites.

    Time frame: Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months

Secondary outcomes

  1. Density of asexual stages and gametocytes, in children 1-60 months

    MORDOR Malawi and Niger Please note: Each outcome will be analyzed separately in each of the two study sites.

    Time frame: Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months

  2. Hemoglobin concentration and presence of anemia (hemoglobin <11 g/dL) in children 1-60 months

    MORDOR Malawi, Tanzania and Niger. Please note: Each outcome will be analyzed separately for each study site.

    Time frame: Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months

  3. Genetic determinants of macrolide resistance in the nasopharynx (eg pneumococcal) in individuals 7-12 years of age

    MORDOR Niger

    Time frame: 24 months

  4. Genetic determinants of macrolide resistance in the nasopharynx (eg pneumococcal) in individuals 1-60 month olds seen in local health clinics for a respiratory complaint

    MORDOR Malawi, Tanzania and Niger. Please note: Each outcome will be analyzed separately for each study site.

    Time frame: 24 months

  5. Rates of acute respiratory illness among children 1-60 months.

    MORDOR Tanzania

    Time frame: 6-24 months after baseline

  6. Presence of the trachoma grades "follicular trachoma" (TF) and "intense inflammatory trachoma" (TI), as defined by the World Health Organization (WHO) simplified grading system, in children 1-60 months

    MORDOR Malawi and Niger Please note: Each outcome will be analyzed separately for each study site.

    Time frame: 24 months

  7. Rates of diarrhea among children (1-60 months)

    MORDOR Tanzania

    Time frame: 6-24 months after baseline

  8. Proportion of rectal/stool isolates with evidence of resistance (in for example E.coli) to macrolides and other antibiotics commonly used to treat pediatric infections among children 1-60 months

    MORDOR Malawi, Tanzania and Niger. Please note: Each outcome will be analyzed separately for each study site.

    Time frame: 6-24 months after baseline; Niger will also report outcomes at 48 months

  9. Proportions of E. coli isolates resistant to macrolides and to antibiotics commonly used to treat pediatric infections among children 1-60 months hospitalized for pneumonia and diarrhea.

    MORDOR Tanzania

    Time frame: 6-24 months after baseline

  10. Studies of intestinal permeability and inflammation, microbial translocation, and immune activation assessed through venous sampling of children 6 months

    MORDOR Malawi

    Time frame: 5 x over 24 weeks after baseline

  11. Studies of intestinal permeability and inflammation, microbial translocation, and immune activation assessed through urine samples for L:M ratios of children 6 months

    MORDOR Malawi

    Time frame: 5 x over 24 weeks after baseline

  12. Studies of intestinal permeability and inflammation, microbial translocation, and immune activation assessed through stool (fecal neopterin) of children 6 months

    MORDOR Malawi

    Time frame: 5 x over 24 weeks after baseline

  13. Nasopharyngeal pneumococcal evidence of beta lactam and macrolide resistance in in children 1-60 months as measured by RNA-sequencing of the resistome

    MORDOR Malawi, Tanzania and Niger. Please note: Each outcome will be analyzed separately for each study site.

    Time frame: Tanzania will report outcomes at 6-24 months. Each site will report outcomes at 24 months; Niger will also report outcomes at 36 months

  14. Nasopharyngeal pneumococcal macrolide resistance determinants (eg erythromycin ribosomal methylase B and mefA), serotype, and multilocus sequence type in children 1-60 months

    MORDOR Niger

    Time frame: 24 months

  15. Microbiome in the stool, nasopharynx, nares, and conjunctiva in children aged 1-59 months, as measured using next generation sequencing. Arms will be compared using Euclidean distance and diversity compared using Simpson's index.

    Investigators will examine the effects of mass azithromycin (pre-treatment and post-treatment) on the human microbiome of African children by performing metagenomic experiments. MORDOR Niger

    Time frame: 24 months

  16. Microbial diversity in the intestinal microbiomes of children aged 1-60 months as measured by using next generation sequencing

    Investigators will examine the effects of mass azithromycin (pre-treatment and post-treatment) on the human microbiome of African children by performing metagenomic experiments. MORDOR Malawi

    Time frame: 24 months

  17. Serology for exposure to exotic pathogens of children aged 1-60 months as measured by lateral flow assays or Multiplex bead array

    MORDOR Malawi

    Time frame: 24 months

  18. Head circumference over time in children aged 1-60 months

    MORDOR Malawi

    Time frame: 24 months

  19. Knee-heel length over time in children aged 1-60 months

    MORDOR Malawi

    Time frame: 24 months

  20. Resistance (in E.coli phenotypically or genetic determinants) in stool of children aged 1-60 months.

    MORDOR Malawi, Tanzania and Niger. Please note: Each outcome will be analyzed separately for each study site.

    Time frame: Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months

  21. Prevalence of carriage of a panel of gastrointestinal parasites (Ancylostoma duodenale, Necator americanus, Ascaris lumbricoides, Trichuris trichiura, Giardia lamblia, Cryptosporidium hominis) of children aged 1-60 months

    MORDOR Malawi

    Time frame: Baseline

  22. Prevalence of helicobacter pylori of children aged 1-60 months

    MORDOR Malawi

    Time frame: Baseline

  23. Antibody response to enteric pathogens and malaria measured with a multiplex bead assay from dried blood spots collected from children 1 - 59 months

    MORDOR Niger

    Time frame: Niger will report outcomes at 36, 48 and 60 months

07

Study locations

6 sites
  • UCSF Proctor Foundation
    San Francisco, California 94143-0944, United States
  • Johns Hopkins University
    Baltimore, Maryland 21205, United States
  • College of Medicine at the University of Malawi, Blantyre
    Blantyre, Malawi
  • The Carter Center, Niger
    Niamey, Niger
  • Kongwa Trachoma Project
    Kongwa, Tanzania
  • London School of Hygiene & Tropical Medicine
    London, United Kingdom
08

References and documents

Publications

  • 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. PubMed 35997979 ↗
  • 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. PubMed 35190534 ↗
  • 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. PubMed 35156069 ↗
  • 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. PubMed 34967883 ↗
  • 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. PubMed 34559801 ↗
  • 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. PubMed 31237871 ↗
  • 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. PubMed 30950493 ↗
  • 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. PubMed 30419040 ↗
  • 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. Erratum In: Open Forum Infect Dis. 2023 Oct 06;10(10):ofad489. doi: 10.1093/ofid/ofad489. PubMed 30151409 ↗
  • 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. PubMed 28402408 ↗
  • 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. PubMed 25858004 ↗

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 17, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02048007
Lead sponsor
University of California, San Francisco
Collaborators
Bill and Melinda Gates Foundation, Johns Hopkins University, London School of Hygiene and Tropical Medicine
Responsible party
Sponsor
First posted
Jan 29, 2014
Start date
Nov 2014
Primary completion
Aug 27, 2020
Completion
Aug 27, 2020
Last update
Mar 17, 2021

Study contacts

Tom M Lietman, MD
principal investigator · University of California, San Francisco
Elodie J Lebas, RN
study director · University of California, San Francisco

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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