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Mortality Reduction After Oral Azithromycin: Morbidity Study (MORDORMorb)

15 mars 2021 uppdaterad av: University of California, San Francisco

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

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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

Studietyp

Interventionell

Inskrivning (Faktisk)

72000

Fas

  • Fas 4

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

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

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

1 månad och äldre (Barn, Vuxen, Äldre vuxen)

Tar emot friska volontärer

Ja

Kön som är behöriga för studier

Allt

Beskrivning

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)

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Fyrdubbla

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Aktiv komparator: 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.
Läkemedel: Azithromycin
Biannual mass oral azithromycin to children
Andra namn:
  • Zithromax
Placebo-jämförare: 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
Läkemedel: Placebo
Biannual mass oral placebo to children

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Presence of malaria parasites on thick blood smear or Rapid Diagnostic Test (RDT) in children 1-60 months
Tidsram: 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.
Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
Fraction of isolates of pneumococcus exhibiting macrolide resistance by nasopharyngeal swabs in children 1-60 months
Tidsram: 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.
Each site will report outcomes at 24 months; Niger will also report outcomes at 36 months
Prevalence of macrolide resistance in the stool as determined by genetic determinants or phenotypic testing
Tidsram: 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.
Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
Fraction of conjunctival swabs yielding ocular chlamydia in children 1-60 months
Tidsram: 24 months
MORDOR Malawi and Niger. Please note: Each outcome will be analyzed separately for each study site.
24 months
Height over time in children aged 1-60 months
Tidsram: 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.
Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
Weight for Height over time in children aged 1-60 months
Tidsram: 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.
Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Density of asexual stages and gametocytes, in children 1-60 months
Tidsram: 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.
Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
Hemoglobin concentration and presence of anemia (hemoglobin <11 g/dL) in children 1-60 months
Tidsram: 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.
Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
Genetic determinants of macrolide resistance in the nasopharynx (eg pneumococcal) in individuals 7-12 years of age
Tidsram: 24 months
MORDOR Niger
24 months
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
Tidsram: 24 months
MORDOR Malawi, Tanzania and Niger. Please note: Each outcome will be analyzed separately for each study site.
24 months
Rates of acute respiratory illness among children 1-60 months.
Tidsram: 6-24 months after baseline
MORDOR Tanzania
6-24 months after baseline
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
Tidsram: 24 months
MORDOR Malawi and Niger Please note: Each outcome will be analyzed separately for each study site.
24 months
Rates of diarrhea among children (1-60 months)
Tidsram: 6-24 months after baseline
MORDOR Tanzania
6-24 months after baseline
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
Tidsram: 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.
6-24 months after baseline; Niger will also report outcomes at 48 months
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.
Tidsram: 6-24 months after baseline
MORDOR Tanzania
6-24 months after baseline
Studies of intestinal permeability and inflammation, microbial translocation, and immune activation assessed through venous sampling of children 6 months
Tidsram: 5 x over 24 weeks after baseline
MORDOR Malawi
5 x over 24 weeks after baseline
Studies of intestinal permeability and inflammation, microbial translocation, and immune activation assessed through urine samples for L:M ratios of children 6 months
Tidsram: 5 x over 24 weeks after baseline
MORDOR Malawi
5 x over 24 weeks after baseline
Studies of intestinal permeability and inflammation, microbial translocation, and immune activation assessed through stool (fecal neopterin) of children 6 months
Tidsram: 5 x over 24 weeks after baseline
MORDOR Malawi
5 x over 24 weeks after baseline
Nasopharyngeal pneumococcal evidence of beta lactam and macrolide resistance in in children 1-60 months as measured by RNA-sequencing of the resistome
Tidsram: 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.
Tanzania will report outcomes at 6-24 months. Each site will report outcomes at 24 months; Niger will also report outcomes at 36 months
Nasopharyngeal pneumococcal macrolide resistance determinants (eg erythromycin ribosomal methylase B and mefA), serotype, and multilocus sequence type in children 1-60 months
Tidsram: 24 months
MORDOR Niger
24 months
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.
Tidsram: 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
24 months
Microbial diversity in the intestinal microbiomes of children aged 1-60 months as measured by using next generation sequencing
Tidsram: 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
24 months
Serology for exposure to exotic pathogens of children aged 1-60 months as measured by lateral flow assays or Multiplex bead array
Tidsram: 24 months
MORDOR Malawi
24 months
Head circumference over time in children aged 1-60 months
Tidsram: 24 months
MORDOR Malawi
24 months
Knee-heel length over time in children aged 1-60 months
Tidsram: 24 months
MORDOR Malawi
24 months
Resistance (in E.coli phenotypically or genetic determinants) in stool of children aged 1-60 months.
Tidsram: 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.
Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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
Tidsram: Baseline
MORDOR Malawi
Baseline
Prevalence of helicobacter pylori of children aged 1-60 months
Tidsram: Baseline
MORDOR Malawi
Baseline
Antibody response to enteric pathogens and malaria measured with a multiplex bead assay from dried blood spots collected from children 1 - 59 months
Tidsram: Niger will report outcomes at 36, 48 and 60 months
MORDOR Niger
Niger will report outcomes at 36, 48 and 60 months

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

University of California, San Francisco

Samarbetspartners

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

Utredare

  • Studierektor: Elodie J Lebas, RN, University of California, San Francisco

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

1 november 2014

Primärt slutförande (Faktisk)

27 augusti 2020

Avslutad studie (Faktisk)

27 augusti 2020

Studieregistreringsdatum

Först inskickad

24 januari 2014

Först inskickad som uppfyllde QC-kriterierna

24 januari 2014

Första postat (Uppskatta)

29 januari 2014

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

17 mars 2021

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

15 mars 2021

Senast verifierad

1 mars 2021

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • OPP1032340-B

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

NEJ

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Ja

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

produkt tillverkad i och exporterad från U.S.A.

Nej

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