CompletedNCT02047981MORDORIMortUpdated Nov 8, 2022Results posted

Mortality Reduction After Oral Azithromycin: Mortality Study

A Phase 4 interventional study of Azithromycin and Placebo in Childhood Mortality, sponsored by University of California, San Francisco. Completed at 6 sites in 5 countries. Open to participants aged 1 Month to 60 Months, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-11-08.

Sponsored by University of California, San Francisco · Phase 4, Interventional, and Treatment

Phase: Phase 4
Study type: Interventional
Enrollment: 190,238
Allocation: Randomized
Ages: 1 Month to 60 Months
Sex: All

Study summary

Our long-term goal is to more precisely define the role of mass azithromycin treatments as an intervention for reducing childhood mortality. We propose a single multi-site (multi-country), cluster-randomized trial comparing communities randomized to oral azithromycin with those randomized to placebo. We hypothesize that mass azithromycin treatments will reduce childhood mortality.

Read the detailed description

We will assess childhood mortality over three years, comparing communities where children aged 1-60 months receive biannual oral azithromycin ("Azithromycin" arm) for two years, to communities where the children receive biannual oral placebo ("Control" arm) for two years. During the third year at the Niger site only, everyone will receive azithromycin.

This is a cluster-randomized trial; at each site, communities within a contiguous area of 300,000 to 600,000 individuals will be randomized to azithromycin or placebo using simple random sampling.

Niger contingency study: In the event that mass distributions of oral azithromycin are proven to reduce mortality in 1-60 month-old children, then we will treat all communities in Niger with mass azithromycin distributions to test whether the intervention continues to reduce childhood mortality after the initial 2 years of mass treatments.

Conditions studied

Childhood Mortality

Browse trials for

Infections 2,093

Keywords

Childhood mortality
Azithromycin
Mass treatment
Infection
Verbal Autopsy

In context

Infections

2,093 studies on the registry are indexed under Infections; 364 are open to participants now.

This study's enrollment of 190,238 is above the median of 113 across 1,304 interventional studies indexed under Infections.

Browse Infections studies →

Lead sponsor

University of California, San Francisco is the lead sponsor of 2,169 studies on the registry; 372 are open to participants now.

Of its 267 completed or terminated interventional studies of FDA-regulated products, 202 (76%) have results posted.

Browse University of California, San Francisco studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 1 Month to 60 Months
Sexes eligible: All
Accepts healthy volunteers: Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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 - All children aged 1-60 months (up to but not including the 5th birthday), as assessed via biannual census.

Exclusion criteria

Exclusion Criteria:

Individuals

Refusal of village chief (for village inclusion), or refusal of parent or guardian (for individual inclusion)

Study design

Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 190,238 participants (actual)

Study arms

Active comparator
Biannual mass oral azithromycin
Comparison of childhood mortality 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. In Niger during year 3, all communities will be offered azithroymcin.
Drug: Azithromycin
Placebo comparator
Biannual mass oral placebo
Comparison of childhood mortality 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 In Niger during year 3, all communities will be offered azithroymcin.
Drug: Placebo

Interventions

DrugAzithromycin
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. In Niger during year 3, all communities will be offered azithroymcin.
Also known as: Zithromax
DrugPlacebo
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. In Niger during year 3, all communities will be offered azithroymcin.

What researchers measure

Primary outcomes

All-cause Mortality Rate in Children Aged 1-60 Months
This is a single multi-site trial, with each country as a secondary analysis. Also, an interim analysis of efficacy and futility will be conducted according to a pre-specified plan in the Statistical Analysis Plan.
Time frame: 24 Months
All-cause Mortality Rate in Children Aged 1-60 Months
This was a pre-specified contingency study in Niger only in which all communities were treated with mass azithromycin during the third year of the study following the primary 24-month endpoint.
Time frame: 36 months

Secondary outcomes

Cause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Niger Only)
Deaths were assessed via biannual population census. A pre-specified outcome was cause of death, assessed by verbal autopsy.
Time frame: 24 Months
Cost-effectiveness of Mass Azithromycin Administration, Per Averted Childhood Death
Cost-effectiveness of Mass Azithromycin Administration, Per Averted Childhood Death during the 24 month phase
Time frame: 24 months
All-cause and Cause-specific Health Clinic Visits in 1-60 Month-old Children
We recorded clinic visits one year prior the study and during the first year of the study and collected outcomes of these visit.
Time frame: 24 months
Cause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Tanzania Only)
At 6-monthly intervals a census of the communities was conducted, and for child deaths a verbal autopsy was performed to ascertain the cause using a standardized diagnostic classification. Mortality due to pneumonia or diarrhea by age group and arm are shown in the outcome measure data table below.
Time frame: 24 Months
Cause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Malawi Only)
Cause-specific mortality by intention-to-treat for the four main inferred causes of death in the study area.
Time frame: 24 Months

Results

Posted Jan 3, 2020

Participant flow

MORDOR Stage I Year 1-2

Participant flow — MORDOR Stage I Year 1-2
Milestone	Biannual Mass Oral Azithromycin	Biannual Mass Oral Placebo
Started	97047	93191
Completed	87650	84474
Not completed	9397	8717

MORDOR Stage II Year 3

Participant flow — MORDOR Stage II Year 3
Milestone	Biannual Mass Oral Azithromycin	Biannual Mass Oral Placebo
Started	37497	33294
Completed	34611	30931
Not completed	2886	2363

Outcome measures

PrimaryAll-cause Mortality Rate in Children Aged 1-60 Months

This is a single multi-site trial, with each country as a secondary analysis. Also, an interim analysis of efficacy and futility will be conducted according to a pre-specified plan in the Statistical Analysis Plan.

Time frame:: 24 Months
Reported as:: Number · deaths per 1000 person-years

All-cause Mortality Rate in Children Aged 1-60 Months
deaths per 1000 person-years	Biannual Mass Oral Azithromycin	Biannual Mass Oral Placebo
All-cause Mortality Rate in Children Aged 1-60 Months	14.6	16.5

PrimaryAll-cause Mortality Rate in Children Aged 1-60 Months

This was a pre-specified contingency study in Niger only in which all communities were treated with mass azithromycin during the third year of the study following the primary 24-month endpoint.

Time frame:: 36 months
Reported as:: Number · deaths per 1000 person-years

All-cause Mortality Rate in Children Aged 1-60 Months
deaths per 1000 person-years	Biannual Mass Oral Azithromycin	Biannual Mass Oral Placebo
All-cause Mortality Rate in Children Aged 1-60 Months	23.3 (21.4 to 25.5)	24.0 (22.1 to 26.3)

SecondaryCause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Niger Only)

Deaths were assessed via biannual population census. A pre-specified outcome was cause of death, assessed by verbal autopsy.

Time frame:: 24 Months
Reported as:: Number · Deaths per 1000 person years

Cause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Niger Only)
Deaths per 1000 person years	Biannual Mass Oral Azithromycin	Biannual Mass Oral Placebo
Injury	0.22 (0.14 to 0.36)	0.23 (0.14 to 0.38)
Malnutrition	0.39 (0.26 to 0.59)	0.42 (0.28 to 0.63)
AIDS	0.12 (0.06 to 0.23)	0.12 (0.06 to 0.24)
Measles	0.30 (0.19 to 0.46)	0.28 (0.17 to 0.45)
Meningitis	0.82 (0.63 to 1.09)	1.22 (0.96 to 1.57)
Dysentery	0.74 (0.55 to 0.98)	1.14 (0.88 to 1.47)
Diarrhea	3.01 (2.59 to 3.49)	3.60 (3.11 to 4.17)
Pertussis	0.04 (0.01 to 0.12)	0.04 (0.01 to 0.14)
Pneumonia	3.27 (2.85 to 3.75)	3.96 (3.46 to 4.53)
Malaria	5.60 (4.97 to 6.32)	7.22 (6.43 to 8.11)
Hemorrhagic fever	0.08 (0.03 to 0.17)	0.06 (0.02 to 0.16)
Other infection	4.24 (3.70 to 4.85)	5.06 (4.44 to 5.78)
Unspecified	1.43 (1.17 to 1.75)	1.81 (1.49 to 2.19)
Total	22.3 (20.9 to 23.9)	27.3 (25.5 to 29.1)

SecondaryCost-effectiveness of Mass Azithromycin Administration, Per Averted Childhood Death

Cost-effectiveness of Mass Azithromycin Administration, Per Averted Childhood Death during the 24 month phase

Time frame:: 24 months
Reported as:: Mean · usd per death averted

Cost-effectiveness of Mass Azithromycin Administration, Per Averted Childhood Death
usd per death averted	Biannual Mass Oral Azithromycin	Biannual Mass Oral Placebo
Cost-effectiveness of Mass Azithromycin Administration, Per Averted Childhood Death	853 (581 to 1719)	0 (0 to 0)

SecondaryAll-cause and Cause-specific Health Clinic Visits in 1-60 Month-old Children

We recorded clinic visits one year prior the study and during the first year of the study and collected outcomes of these visit.

Time frame:: 24 months
Reported as:: Number · post-treatment clinical visits

All-cause and Cause-specific Health Clinic Visits in 1-60 Month-old Children
post-treatment clinical visits	Biannual Mass Oral Azithromycin	Biannual Mass Oral Placebo
All-cause and Cause-specific Health Clinic Visits in 1-60 Month-old Children	5229	7647

SecondaryCause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Tanzania Only)

At 6-monthly intervals a census of the communities was conducted, and for child deaths a verbal autopsy was performed to ascertain the cause using a standardized diagnostic classification. Mortality due to pneumonia or diarrhea by age group and arm are shown in the outcome measure data table below.

Time frame:: 24 Months
Reported as:: Number · deaths per 100 person-years

Cause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Tanzania Only)
deaths per 100 person-years	Biannual Mass Oral Azithromycin	Biannual Mass Oral Placebo
Age group Mortality: 1- 5 months	0.46	0.90
Age group Mortality: 6- 11 months	0.47	0.56
Age group Mortality: 12 - 23 months	0.29	0.29
Age group Mortality: 24 - 59 months	0.15	0.10

SecondaryCause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Malawi Only)

Cause-specific mortality by intention-to-treat for the four main inferred causes of death in the study area.

Time frame:: 24 Months
Reported as:: Number · deaths per 1000 person-years

Cause-specific Mortality Rate in Children Aged 1-60 Months, as Assessed From Verbal Autopsy (Malawi Only)
deaths per 1000 person-years	Biannual Mass Oral Azithromycin	Biannual Mass Oral Placebo
Pneumonia	1.15 (0.92 to 1.44)	1.40 (1.15 to 1.72)
Malaria	3.68 (3.25 to 4.17)	3.84 (3.40 to 4.34)
HIV/AIDS	1.06 (0.84 to 1.34)	1.54 (1.27 to 1.87)
Diarrhoea	0.67 (0.50 to 0.90)	0.72 (0.54 to 0.95)

Adverse events

Collected over 36 months.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Biannual Mass Oral Azithromycin	3,262/97,047 (3.4%)	3,273/97,047 (3.4%)	0/97,047 (0%)
Biannual Mass Oral Placebo	3,392/93,191 (3.6%)	3,400/93,191 (3.6%)	0/93,191 (0%)

Most frequent serious events

Showing 8 of 9

Most frequent serious events
Event	Biannual Mass Oral Azithromycin	Biannual Mass Oral Placebo
DeathGeneral disorders	3262/97047	3392/93191
MalariaInfections and infestations	4/97047	3/93191
Suspected dehydrationGeneral disorders	0/97047	2/93191
ARIRespiratory, thoracic and mediastinal disorders	0/97047	2/93191
DiarrheaGastrointestinal disorders	0/97047	1/93191
Suspected ileusGastrointestinal disorders	1/97047	0/93191
ComaGeneral disorders	1/97047	0/93191
PneumoniaRespiratory, thoracic and mediastinal disorders	1/97047	0/93191

Baseline characteristics

Age, Customized
Age, Customized(Participants)	Biannual Mass Oral Azithromycin	Biannual Mass Oral Placebo	Total
Age group — 1-5 months	7135	6870	14005
Age group — 6-11 months	12777	12318	25095
Age group — 12-23 months	18557	17886	36443
Age group — 24-59 months	58578	56117	114695

Sex: Female, Male
Sex: Female, Male(Participants)	Biannual Mass Oral Azithromycin	Biannual Mass Oral Placebo	Total
Female	47901	46019	93920
Male	49146	47172	96318

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Biannual Mass Oral Azithromycin	Biannual Mass Oral Placebo	Total
American Indian or Alaska Native	0	0	0
Asian	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	97047	93191	190238
White	0	0	0
More than one race	0	0	0
Unknown or Not Reported	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Biannual Mass Oral Azithromycin	Biannual Mass Oral Placebo	Total
Niger	40345	35747	76092
Malawi	39386	39534	78920
Tanzania	17316	17910	35226

Number of communities
Number of communities(communities)	Biannual Mass Oral Azithromycin	Biannual Mass Oral Placebo	Total
Number	762	750	1512

Study locations

6 sites

UCSF Proctor Foundation
San Francisco, California 94143, United States
Johns Hopkins University
Baltimore, Maryland 21205, United States
College of Medicine at the University of Malawi, Blantyre
Blantyre, Malawi
The Carter Center, Niger
Niamey, Niger
Kongwa Trachoma Project
Kongwa, Tanzania
London School of Hygiene & Tropical Medicine
London, United Kingdom

References and documents

Publications

Pickering H, Hart JD, Burr S, Stabler R, Maleta K, Kalua K, Bailey RL, Holland MJ. Impact of azithromycin mass drug administration on the antibiotic-resistant gut microbiome in children: a randomized, controlled trial. Gut Pathog. 2022 Jan 6;14(1):5. doi: 10.1186/s13099-021-00478-6. PubMed 34991704 ↗
Arzika AM, Maliki R, Abdou A, Mankara AK, Harouna AN, Cook C, Hinterwirth A, Worden L, Zhong L, Chen C, Ruder K, Zhou Z, Lebas E, O'Brien KS, Oldenburg CE, Le V, Arnold BF, Porco TC, Keenan JD, Lietman TM, Doan T. Gut Resistome of Preschool Children After Prolonged Mass Azithromycin Distribution: A Cluster-randomized Trial. Clin Infect Dis. 2021 Oct 5;73(7):1292-1295. doi: 10.1093/cid/ciab485. PubMed 34037753 ↗
Doan T, Worden L, Hinterwirth A, Arzika AM, Maliki R, Abdou A, Zhong L, Chen C, Cook C, Lebas E, O'Brien KS, Oldenburg CE, Chow ED, Porco TC, Lipsitch M, Keenan JD, Lietman TM. Macrolide and Nonmacrolide Resistance with Mass Azithromycin Distribution. N Engl J Med. 2020 Nov 12;383(20):1941-1950. doi: 10.1056/NEJMoa2002606. PubMed 33176084 ↗
O'Brien KS, Arzika AM, Maliki R, Manzo F, Mamkara AK, Lebas E, Cook C, Bailey RL, West SK, Oldenburg CE, Porco TC, Arnold B, Keenan JD, Lietman TM; MORDOR Study Group. Biannual azithromycin distribution and child mortality among malnourished children: A subgroup analysis of the MORDOR cluster-randomized trial in Niger. PLoS Med. 2020 Sep 15;17(9):e1003285. doi: 10.1371/journal.pmed.1003285. eCollection 2020 Sep. PubMed 32931496 ↗
Doan T, Hinterwirth A, Arzika AM, Worden L, Chen C, Zhong L, Oldenburg CE, Keenan JD, Lietman TM. Reduction of Coronavirus Burden With Mass Azithromycin Distribution. Clin Infect Dis. 2020 Nov 19;71(16):2282-2284. doi: 10.1093/cid/ciaa606. PubMed 32426812 ↗
Keenan JD, Arzika AM, Maliki R, Elh Adamou S, Ibrahim F, Kiemago M, Galo NF, Lebas E, Cook C, Vanderschelden B, Bailey RL, West SK, Porco TC, Lietman TM; MORDOR-Niger Study Group. Cause-specific mortality of children younger than 5 years in communities receiving biannual mass azithromycin treatment in Niger: verbal autopsy results from a cluster-randomised controlled trial. Lancet Glob Health. 2020 Feb;8(2):e288-e295. doi: 10.1016/S2214-109X(19)30540-6. PubMed 31981558 ↗
Bloch EM, Munoz B, Mrango Z, Weaver J, Mboera LEG, Lietman TM, Sullivan DJ Jr, West SK. The impact on malaria of biannual treatment with azithromycin in children age less than 5 years: a prospective study. Malar J. 2019 Aug 23;18(1):284. doi: 10.1186/s12936-019-2914-8. PubMed 31443654 ↗
Doan T, Arzika AM, Hinterwirth A, Maliki R, Zhong L, Cummings S, Sarkar S, Chen C, Porco TC, Keenan JD, Lietman TM; MORDOR Study Group. Macrolide Resistance in MORDOR I - A Cluster-Randomized Trial in Niger. N Engl J Med. 2019 Jun 6;380(23):2271-2273. doi: 10.1056/NEJMc1901535. No abstract available. PubMed 31167060 ↗
Keenan JD, Arzika AM, Maliki R, Boubacar N, Elh Adamou S, Moussa Ali M, Cook C, Lebas E, Lin Y, Ray KJ, O'Brien KS, Doan T, Oldenburg CE, Callahan EK, Emerson PM, Porco TC, Lietman TM. Longer-Term Assessment of Azithromycin for Reducing Childhood Mortality in Africa. N Engl J Med. 2019 Jun 6;380(23):2207-2214. doi: 10.1056/NEJMoa1817213. PubMed 31167050 ↗
Porco TC, Hart J, Arzika AM, Weaver J, Kalua K, Mrango Z, Cotter SY, Stoller NE, O'Brien KS, Fry DM, Vanderschelden B, Oldenburg CE, West SK, Bailey RL, Keenan JD, Lietman TM; Macrolides Oraux pour Reduire les Deces avec un Oeil sur la Resistance (MORDOR) Study Group. Mass Oral Azithromycin for Childhood Mortality: Timing of Death After Distribution in the MORDOR Trial. Clin Infect Dis. 2019 May 30;68(12):2114-2116. doi: 10.1093/cid/ciy973. PubMed 30561577 ↗
Keenan JD, Bailey RL, West SK, Arzika AM, Hart J, Weaver J, Kalua K, Mrango Z, Ray KJ, Cook C, Lebas E, O'Brien KS, Emerson PM, Porco TC, Lietman TM; MORDOR Study Group. Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa. N Engl J Med. 2018 Apr 26;378(17):1583-1592. doi: 10.1056/NEJMoa1715474. PubMed 29694816 ↗
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. PubMed 25858004 ↗

Study documents

Study protocol ↗ · Jun 27, 2018
Statistical analysis plan ↗ · Jul 15, 2019

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Nov 8, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02047981
Lead sponsor: University of California, San Francisco
Collaborators: Bill and Melinda Gates Foundation, Johns Hopkins University, London School of Hygiene and Tropical Medicine
Responsible party: Sponsor
First posted: Jan 29, 2014
Start date: Dec 2014
Primary completion: Sep 2018
Completion: Sep 2018
Results posted: Jan 3, 2020
Last update: Nov 8, 2022

Study contacts

Tom M Lietman, MD

principal investigator · University of California, San Francisco

Elodie J Lebas, RN

study director · University of California, San Francisco

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Oct 2022. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Azithromycin

Other studies in this condition

Infections →

Other studies from this sponsor

University of California, San Francisco →

Start the discussion