Childhood MortalityPhase 4MORDORMorbNCT02048007
Mortality Reduction After Oral Azithromycin: Morbidity Study
A Phase 4 study testing Azithromycin in people with Childhood Mortality, run by University of California, San Francisco at 6 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 month and olderHealthy volunteers can take part
- Conditions the study is for
- Childhood Mortality
- What is being tested?
- Azithromycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72,000 participants
- Where
- 6 sitesin 5 countries
- Study dates
- Nov 2014to 27 Aug 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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):
Show all 12Show fewer
- 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
Who cannot join
- 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)
Trial locations and contacts
6 sites in 5 countries.
6 sites in 5 countries
United States2 sites
Johns Hopkins University
Baltimore, Maryland, 21205
UCSF Proctor Foundation
San Francisco, California, 94143-0944
Malawi1 site
College of Medicine at the University of Malawi, Blantyre
Blantyre
United Kingdom1 site
London School of Hygiene & Tropical Medicine
London
About this study
Official title: 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.
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
- Conditions
- Childhood Mortality
- Being tested
- Azithromycin, Placebo
- Keywords
- Childhood mortality, Azithromycin, Mass treatment, Infection, Bacterial infections, Trachoma, Chlamydia infections, Malaria, Diarrhea, Respiratory Infections, Antibiotic resistance, Verbal Autopsy, Microbiome
- Medical subject headings
- Infections, Bacterial Infections, Trachoma, Chlamydia Infections, Malaria, Diarrhea, Respiratory Tract Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzithromycinDrug
Also called Zithromax
Biannual mass oral azithromycin to children
PlaceboDrug
Biannual mass oral placebo to children
| Study group | Role | What they receive |
|---|---|---|
| Biannual mass oral azithromycin | Active comparator | 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. Receives: Drug: Azithromycin |
| Biannual mass oral placebo | Placebo comparator | 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 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
MORDOR Malawi, Tanzania and Niger. Please note: Each outcome will be analyzed separately for each study site.
Measured: 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
MORDOR Malawi, Tanzania and Niger. Please note: Each outcome will be analyzed separately for each study site.
Measured: 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
MORDOR Malawi and Niger. Please note: Each outcome will be analyzed separately for each study site.
Measured: 24 months
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.
Measured: 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
MORDOR Malawi and Niger Please note:Each outcome will be analyzed separately in each of the two study sites.
Measured: Each site will report outcomes at 24 months; Niger will also report outcomes at 48 months
Secondary outcomes (23)
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.
Measured: 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
MORDOR Malawi, Tanzania and Niger. Please note: Each outcome will be analyzed separately for each study site.
Measured: 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
MORDOR Niger
Measured: 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
MORDOR Malawi, Tanzania and Niger. Please note: Each outcome will be analyzed separately for each study site.
Measured: 24 months
Rates of acute respiratory illness among children 1-60 months.
MORDOR Tanzania
Measured: 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
MORDOR Malawi and Niger Please note: Each outcome will be analyzed separately for each study site.
Measured: 24 months
Rates of diarrhea among children (1-60 months)
MORDOR Tanzania
Measured: 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
MORDOR Malawi, Tanzania and Niger. Please note: Each outcome will be analyzed separately for each study site.
Measured: 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.
MORDOR Tanzania
Measured: 6-24 months after baseline
Studies of intestinal permeability and inflammation, microbial translocation, and immune activation assessed through venous sampling of children 6 months
MORDOR Malawi
Measured: 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
MORDOR Malawi
Measured: 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
MORDOR Malawi
Measured: 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
MORDOR Malawi, Tanzania and Niger. Please note: Each outcome will be analyzed separately for each study site.
Measured: 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
MORDOR Niger
Measured: 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.
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
Measured: 24 months
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
Measured: 24 months
Serology for exposure to exotic pathogens of children aged 1-60 months as measured by lateral flow assays or Multiplex bead array
MORDOR Malawi
Measured: 24 months
Head circumference over time in children aged 1-60 months
MORDOR Malawi
Measured: 24 months
Knee-heel length over time in children aged 1-60 months
MORDOR Malawi
Measured: 24 months
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.
Measured: 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
MORDOR Malawi
Measured: Baseline
Prevalence of helicobacter pylori of children aged 1-60 months
MORDOR Malawi
Measured: Baseline
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
Measured: Niger will report outcomes at 36, 48 and 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2014 (estimated)
- Study startNov 2014
- Primary completion27 Aug 2020
- Study completion27 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Childhood MortalityStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 72,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation, Johns Hopkins University, London School of Hygiene and Tropical Medicine
- Responsible party
- Sponsor
- Investigators
- Tom M Lietman, MD, Principal investigator, University of California, San FranciscoElodie J Lebas, RN, Study director, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02048007
- Sponsor's protocol ID
- OPP1032340-B
- Acronym
- MORDORMorb
- Status last verified
- Mar 2021
- First submitted
- 24 Jan 2014
- Last updated
- 17 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Arzika AM, Abdou A, Maliki R, Lebas E, Cook C, Vanderschelden B, O'Brien KS, Cotter SY, Varnado NE, Callahan EK, Bailey RL, West SK, Rosenthal PJ, Porco TC, Lietman TM, Keenan JD; MORDOR-Niger Study Group. Biannual Mass Azithromycin Distributions for Preschool Children and Malaria Parasitemia: A Secondary Analysis of the MORDOR Cluster Randomized Trial. JAMA Netw Open. 2025 Aug 1;8(8):e2527148. doi: 10.1001/jamanetworkopen.2025.27148.
PubMed 40824641Liu J, Brennhofer SA, Zhang J, Stroup S, Pholwat S, Arzika AM, Maliki R, Abdou A, Lebas E, O'Brien KS, Arnold BF, Keenan JD, Lietman TM, Platts-Mills JA, Rogawski McQuade ET, Houpt ER. Effect of biannual azithromycin on respiratory pathogens among symptomatic children: results from the randomised Macrolides Oraux pour Reduire les Deces avec un Oeil sur la Resistance (MORDOR) I trial. BMJ Glob Health. 2025 Feb 10;10(2):e016043. doi: 10.1136/bmjgh-2024-016043.
PubMed 39929535Arzika 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 35997979Arzika 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 35190534Hart 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 35156069Arzika 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 34967883Bloch 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 34559801Arzika 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 31237871West 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 30950493Oldenburg 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 30419040Doan 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.
PubMed 30151409Doan 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 28402408Porco 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
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating Impact of Azithromycin Mass Drug Administrations on All-cause Mortality and Antibiotic Resistance: Morbidity Study
- ClinicalTrials.gov ID
- NCT02048007
- Acronym / sponsor ID
- MORDORMorb / OPP1032340-B
- Conditions
- Childhood Mortality
- Keywords
- Childhood mortality, Azithromycin, Mass treatment, Infection, Bacterial infections, Trachoma, Chlamydia infections, Malaria
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72,000 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Bill and Melinda Gates Foundation, Johns Hopkins University, London School of Hygiene and Tropical Medicine
- Study start
- Nov 2014 (actual)
- Primary completion
- 27 Aug 2020 (actual)
- Study completion
- 27 Aug 2020 (actual)
- First posted
- 29 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Biannual mass oral azithromycin | Active comparator | Drug: AzithromycinComparison 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 placebo | Placebo comparator | Drug: PlaceboComparison 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 |
Who may qualify
- Ages
- 1 month and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
- 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
Key exclusion criteria (4 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzithromycinAlso: ZithromaxBiannual mass oral azithromycin to children | Drug | Biannual mass oral azithromycin |
| PlaceboBiannual mass oral placebo to children | Drug | Biannual mass oral placebo |
Primary outcome
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.
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.
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.
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.
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.
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.
23 secondary outcomes
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
Genetic determinants of macrolide resistance in the nasopharynx (eg pneumococcal) in individuals 7-12 years of age
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
Rates of acute respiratory illness among children 1-60 months.
Time frame: 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
Time frame: 24 months
Rates of diarrhea among children (1-60 months)
Time frame: 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
Time frame: 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.
Time frame: 6-24 months after baseline
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
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
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
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
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
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
Microbial diversity in the intestinal microbiomes of children aged 1-60 months as measured by using next generation sequencing
Time frame: 24 months
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
Head circumference over time in children aged 1-60 months
Time frame: 24 months
Knee-heel length over time in children aged 1-60 months
Time frame: 24 months
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
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
Prevalence of helicobacter pylori of children aged 1-60 months
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2021.
- Derived from this study: PubMed 40824641Arzika AM, Abdou A, Maliki R, Lebas E, Cook C, Vanderschelden B, O'Brien KS, Cotter SY, Varnado NE, Callahan EK, Bailey RL, West SK, Rosenthal PJ, Porco TC, Lietman TM, Keenan JD; MORDOR-Niger Study Group. Biannual Mass Azithromycin Distributions for Preschool Children and Malaria Parasitemia: A Secondary Analysis of the MORDOR Cluster Randomized Trial. JAMA Netw Open. 2025 Aug 1;8(8):e2527148. doi: 10.1001/jamanetworkopen.2025.27148.
- Derived from this study: PubMed 39929535Liu J, Brennhofer SA, Zhang J, Stroup S, Pholwat S, Arzika AM, Maliki R, Abdou A, Lebas E, O'Brien KS, Arnold BF, Keenan JD, Lietman TM, Platts-Mills JA, Rogawski McQuade ET, Houpt ER. Effect of biannual azithromycin on respiratory pathogens among symptomatic children: results from the randomised Macrolides Oraux pour Reduire les Deces avec un Oeil sur la Resistance (MORDOR) I trial. BMJ Glob Health. 2025 Feb 10;10(2):e016043. doi: 10.1136/bmjgh-2024-016043.
- Derived from this study: PubMed 35997979Arzika 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.
- Derived from this study: PubMed 35190534Arzika 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.
- Derived from this study: PubMed 35156069Hart 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.
- Derived from this study: PubMed 34967883Arzika 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.
- Derived from this study: PubMed 34559801Bloch 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.
- Derived from this study: PubMed 31237871Arzika 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.
- Derived from this study: PubMed 30950493West 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.
- Derived from this study: PubMed 30419040Oldenburg 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.
- Derived from this study: PubMed 30151409Doan 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.
- Derived from this study: PubMed 28402408Doan 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tom M Lietman, MD principal investigator
University of California, San Francisco
Elodie J Lebas, RN study director
University of California, San Francisco
6 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Azithromycin in people with Childhood Mortality, run by University of California, San Francisco at 6 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Malawi, Niger, Tanzania, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02048007, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2021.