Mortality Reduction After Oral Azithromycin: Morbidity Study (MORDORMorb)
15 marzo 2021 aggiornato da: 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.
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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
Tipo di studio
Interventistico
Iscrizione (Effettivo)
72000
Fase
- Fase 4
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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Blantyre, Malawi
- College of Medicine at the University of Malawi, Blantyre
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Niamey, Niger
- The Carter Center, Niger
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London, Regno Unito
- London School of Hygiene & Tropical Medicine
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California
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San Francisco, California, Stati Uniti, 94143-0944
- UCSF Proctor Foundation
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Maryland
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Baltimore, Maryland, Stati Uniti, 21205
- Johns Hopkins University
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Kongwa, Tanzania
- Kongwa Trachoma Project
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
1 mese e precedenti (Bambino, Adulto, Adulto più anziano)
Accetta volontari sani
Sì
Sessi ammissibili allo studio
Tutto
Descrizione
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)
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Quadruplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Comparatore attivo: 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. |
Biannual mass oral azithromycin to children
Altri nomi:
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Comparatore placebo: 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 |
Biannual mass oral placebo to children
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Presence of malaria parasites on thick blood smear or Rapid Diagnostic Test (RDT) in children 1-60 months
Lasso di tempo: Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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MORDOR Malawi, Tanzania and Niger.
Please note: Each outcome will be analyzed separately for each study site.
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Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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Fraction of isolates of pneumococcus exhibiting macrolide resistance by nasopharyngeal swabs in children 1-60 months
Lasso di tempo: 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.
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Each site will report outcomes at 24 months; Niger will also report outcomes at 36 months
|
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Prevalence of macrolide resistance in the stool as determined by genetic determinants or phenotypic testing
Lasso di tempo: 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
Lasso di tempo: 24 months
|
MORDOR Malawi and Niger.
Please note: Each outcome will be analyzed separately for each study site.
|
24 months
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Height over time in children aged 1-60 months
Lasso di tempo: 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.
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Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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Weight for Height over time in children aged 1-60 months
Lasso di tempo: 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.
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Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Density of asexual stages and gametocytes, in children 1-60 months
Lasso di tempo: 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.
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Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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Hemoglobin concentration and presence of anemia (hemoglobin <11 g/dL) in children 1-60 months
Lasso di tempo: Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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MORDOR Malawi, Tanzania and Niger.
Please note: Each outcome will be analyzed separately for each study site.
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Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
|
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Genetic determinants of macrolide resistance in the nasopharynx (eg pneumococcal) in individuals 7-12 years of age
Lasso di tempo: 24 months
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MORDOR Niger
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24 months
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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
Lasso di tempo: 24 months
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MORDOR Malawi, Tanzania and Niger.
Please note: Each outcome will be analyzed separately for each study site.
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24 months
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Rates of acute respiratory illness among children 1-60 months.
Lasso di tempo: 6-24 months after baseline
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MORDOR Tanzania
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6-24 months after baseline
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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
Lasso di tempo: 24 months
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MORDOR Malawi and Niger Please note: Each outcome will be analyzed separately for each study site.
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24 months
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Rates of diarrhea among children (1-60 months)
Lasso di tempo: 6-24 months after baseline
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MORDOR Tanzania
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6-24 months after baseline
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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
Lasso di tempo: 6-24 months after baseline; Niger will also report outcomes at 48 months
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MORDOR Malawi, Tanzania and Niger.
Please note: Each outcome will be analyzed separately for each study site.
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6-24 months after baseline; Niger will also report outcomes at 48 months
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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.
Lasso di tempo: 6-24 months after baseline
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MORDOR Tanzania
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6-24 months after baseline
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Studies of intestinal permeability and inflammation, microbial translocation, and immune activation assessed through venous sampling of children 6 months
Lasso di tempo: 5 x over 24 weeks after baseline
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MORDOR Malawi
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5 x over 24 weeks after baseline
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Studies of intestinal permeability and inflammation, microbial translocation, and immune activation assessed through urine samples for L:M ratios of children 6 months
Lasso di tempo: 5 x over 24 weeks after baseline
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MORDOR Malawi
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5 x over 24 weeks after baseline
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Studies of intestinal permeability and inflammation, microbial translocation, and immune activation assessed through stool (fecal neopterin) of children 6 months
Lasso di tempo: 5 x over 24 weeks after baseline
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MORDOR Malawi
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5 x over 24 weeks after baseline
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Nasopharyngeal pneumococcal evidence of beta lactam and macrolide resistance in in children 1-60 months as measured by RNA-sequencing of the resistome
Lasso di tempo: Tanzania will report outcomes at 6-24 months. Each site will report outcomes at 24 months; Niger will also report outcomes at 36 months
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MORDOR Malawi, Tanzania and Niger.
Please note: Each outcome will be analyzed separately for each study site.
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Tanzania will report outcomes at 6-24 months. Each site will report outcomes at 24 months; Niger will also report outcomes at 36 months
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Nasopharyngeal pneumococcal macrolide resistance determinants (eg erythromycin ribosomal methylase B and mefA), serotype, and multilocus sequence type in children 1-60 months
Lasso di tempo: 24 months
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MORDOR Niger
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24 months
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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.
Lasso di tempo: 24 months
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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
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Microbial diversity in the intestinal microbiomes of children aged 1-60 months as measured by using next generation sequencing
Lasso di tempo: 24 months
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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
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Serology for exposure to exotic pathogens of children aged 1-60 months as measured by lateral flow assays or Multiplex bead array
Lasso di tempo: 24 months
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MORDOR Malawi
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24 months
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Head circumference over time in children aged 1-60 months
Lasso di tempo: 24 months
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MORDOR Malawi
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24 months
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Knee-heel length over time in children aged 1-60 months
Lasso di tempo: 24 months
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MORDOR Malawi
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24 months
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Resistance (in E.coli phenotypically or genetic determinants) in stool of children aged 1-60 months.
Lasso di tempo: Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
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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
|
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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
Lasso di tempo: Baseline
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MORDOR Malawi
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Baseline
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Prevalence of helicobacter pylori of children aged 1-60 months
Lasso di tempo: Baseline
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MORDOR Malawi
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Baseline
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Antibody response to enteric pathogens and malaria measured with a multiplex bead assay from dried blood spots collected from children 1 - 59 months
Lasso di tempo: Niger will report outcomes at 36, 48 and 60 months
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MORDOR Niger
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Niger will report outcomes at 36, 48 and 60 months
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Collaboratori
Investigatori
- Direttore dello studio: Elodie J Lebas, RN, University of California, San Francisco
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Pubblicazioni generali
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio (Effettivo)
1 novembre 2014
Completamento primario (Effettivo)
27 agosto 2020
Completamento dello studio (Effettivo)
27 agosto 2020
Date di iscrizione allo studio
Primo inviato
24 gennaio 2014
Primo inviato che soddisfa i criteri di controllo qualità
24 gennaio 2014
Primo Inserito (Stima)
29 gennaio 2014
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
17 marzo 2021
Ultimo aggiornamento inviato che soddisfa i criteri QC
15 marzo 2021
Ultimo verificato
1 marzo 2021
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- OPP1032340-B
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
NO
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Sì
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
No
prodotto fabbricato ed esportato dagli Stati Uniti
No
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .