Mortality Reduction After Oral Azithromycin: Morbidity Study

• Register: ClinicalTrials.gov
• Last refreshed on: 29 March 2021
• Main ID: NCT02048007
• Date of registration: 24/01/2014
• Prospective Registration: Yes
• Primary sponsor: University of California, San Francisco
• Public title: Mortality Reduction After Oral Azithromycin: Morbidity Study MORDORMorb
• Scientific title: Evaluating Impact of Azithromycin Mass Drug Administrations on All-cause Mortality and Antibiotic Resistance: Morbidity Study
• Date of first enrolment: November 2014
• Target sample size: 72000
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02048007
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 4

Countries of recruitment

Malawi, Niger, Tanzania, United Kingdom, United States

Contacts

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

• Name: Tom M Lietman, MD
• Affiliation: University of California, San Francisco

Key inclusion & exclusion criteria

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)



Age minimum: 1 Month
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Childhood Mortality

Intervention(s)

Drug: Placebo

Drug: Azithromycin

Primary Outcome(s)

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]

Fraction of conjunctival swabs yielding ocular chlamydia in children 1-60 months [Time Frame: 24 months]

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]

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]

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]

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]

Secondary Outcome(s)

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]

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]

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]

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]

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]

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]

Head circumference over time in children aged 1-60 months [Time Frame: 24 months]

Microbial diversity in the intestinal microbiomes of children aged 1-60 months as measured by using next generation sequencing [Time Frame: 24 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. [Time Frame: 6-24 months after baseline]

Genetic determinants of macrolide resistance in the nasopharynx (eg pneumococcal) in individuals 7-12 years of age [Time Frame: 24 months]

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]

Rates of diarrhea among children (1-60 months) [Time Frame: 6-24 months 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 [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]

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]

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]

Rates of acute respiratory illness among children 1-60 months. [Time Frame: 6-24 months after baseline]

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]

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]

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]

Prevalence of helicobacter pylori of children aged 1-60 months [Time Frame: Baseline]

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]

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]

Knee-heel length over time in children aged 1-60 months [Time Frame: 24 months]

Secondary ID(s)

OPP1032340-B

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Johns Hopkins University

Bill and Melinda Gates Foundation

London School of Hygiene and Tropical Medicine