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Completed

NCT Number: NCT02048007

Mortality Reduction After Oral Azithromycin: Morbidity Study

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.

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Key information

Conditions

Childhood Mortality Bacterial Infections Bacterial Infections and Mycoses Chlamydia Infections Chlamydiaceae Infections Communicable Diseases Conjunctival Diseases Conjunctivitis Conjunctivitis, Bacterial Corneal Diseases Diarrhea Eye Diseases Eye Infections Eye Infections, Bacterial Genital Diseases Gram-Negative Bacterial Infections Infections Malaria Mosquito-Borne Diseases Parasitic Diseases Pathological Conditions, Signs and Symptoms Protozoan Infections Respiratory Tract Diseases Respiratory Tract Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Bacterial Signs and Symptoms Signs and Symptoms, Digestive Trachoma Urogenital Diseases Vector Borne Diseases

Age range

1 month and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

College of Medicine at the University of Malawi, Blantyre, Blantyre, Malawi

Loading trial locations.

About this study

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

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Azithromycin

Drug

Biannual mass oral azithromycin to children

Other names: Zithromax

Placebo

Drug

Biannual mass oral placebo to children

Primary outcomes

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

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

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

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

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

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

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

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

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

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

    Time frame: 24 months

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

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

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

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

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

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

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

Secondary outcomes

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

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

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

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

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

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

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

    Time frame: 24 months

    MORDOR Niger

  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

    Time frame: 24 months

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

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

    Time frame: 6-24 months after baseline

    MORDOR Tanzania

  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

    Time frame: 24 months

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

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

    Time frame: 6-24 months after baseline

    MORDOR Tanzania

  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

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

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

  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.

    Time frame: 6-24 months after baseline

    MORDOR Tanzania

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

    Time frame: 5 x over 24 weeks after baseline

    MORDOR Malawi

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

    Time frame: 5 x over 24 weeks after baseline

    MORDOR Malawi

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

    Time frame: 5 x over 24 weeks after baseline

    MORDOR Malawi

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

    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

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

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

    Time frame: 24 months

    MORDOR Niger

  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.

    Time frame: 24 months

    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

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

    Time frame: 24 months

    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

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

    Time frame: 24 months

    MORDOR Malawi

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

    Time frame: 24 months

    MORDOR Malawi

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

    Time frame: 24 months

    MORDOR Malawi

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

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

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

  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

    Time frame: Baseline

    MORDOR Malawi

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

    Time frame: Baseline

    MORDOR Malawi

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

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

    MORDOR Niger

Sponsors and collaborators

Lead sponsor

University of California, San Francisco

Other

Collaborators

  • Bill and Melinda Gates Foundation
  • Johns Hopkins University
  • London School of Hygiene and Tropical Medicine

Registry information

Official study title

Evaluating Impact of Azithromycin Mass Drug Administrations on All-cause Mortality and Antibiotic Resistance: Morbidity Study

Acronym: MORDORMorb

Important dates

Study start
2014
Primary completion
2020
Study completion
2020
First posted
Jan 29, 2014
Registry last updated
Mar 17, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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