Mortality Reduction After Oral Azithromycin: Mortality Study

NCT02047981 | Completed Phase 4 Results DMC

• 1 other identifier: OPP1032340-A
• Study Type: interventional
• Target: 190,238
• Locations: 5 countries
• Sites: 6

Brief 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.

Conditions

Childhood Mortality

Keywords

Childhood mortality; Azithromycin; Mass treatment; Infection; Verbal Autopsy

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  36 months

Secondary Outcomes (5)

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

  24 Months

• Cost-effectiveness of Mass Azithromycin Administration, Per Averted Childhood Death

  24 months

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

  24 months

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

  24 Months

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

  24 Months

Study Arms (2)

Biannual mass oral azithromycin

ACTIVE COMPARATOR

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

Biannual mass oral placebo

PLACEBO COMPARATOR

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

Azithromycin DRUG

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

Biannual mass oral azithromycin

Placebo DRUG

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.

Biannual mass oral placebo

Eligibility Criteria

• Age: 1 Month - 60 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• Individuals

Sponsors & Collaborators

• University of California, San Francisco: lead
• Bill and Melinda Gates Foundation: collaborator
• Johns Hopkins University: collaborator
• London School of Hygiene and Tropical Medicine: collaborator

Study Sites (6)

UCSF Proctor Foundation

San Francisco, California, 94143, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

College of Medicine at the University of Malawi, Blantyre

Blantyre, Malawi

Location

The Carter Center, Niger

Niamey, Niger

Location

Kongwa Trachoma Project

Kongwa, Tanzania

Location

London School of Hygiene & Tropical Medicine

London, United Kingdom

Location

Related Publications (16)

• Hinterwirth A, Chen C, Yan D, Zhong L, Zhou Z, Liu Y, Keenan J, O'Brien KS, Lebas E, Porco TC, Lietman TM, Doan T. Co-selection of genetic antibiotic resistance in Streptococcus pneumoniae after repeated azithromycin mass drug administrations in Niger. Antimicrob Agents Chemother. 2025 Dec 23:e0156225. doi: 10.1128/aac.01562-25. Online ahead of print.

  PMID: 41432154 DERIVED

• Peterson B, Arzika AM, Amza A, Maliki R, Karamba AM, Moussa M, Kemago M, Liu Z, Houpt E, Liu J, Pholwat S, Doan T, Porco TC, Keenan JD, Lietman TM, O'Brien KS. Assessment of Spillover of Antimicrobial Resistance to Untreated Children 7-12 Years Old After Mass Drug Administration of Azithromycin for Child Survival in Niger: A Secondary Analysis of the MORDOR Cluster-Randomized Trial. Clin Infect Dis. 2024 Nov 22;79(5):1136-1143. doi: 10.1093/cid/ciae267.

  PMID: 38739754 DERIVED

• Arzika AM, Abdou A, Maliki R, Beido N, Kadri B, Harouna AN, Galo AN, Alio MK, Lebas E, Oldenburg CE, O'Brien KS, Chen C, Zhong L, Zhou Z, Yan D, Hinterwirth A, Keenan JD, Porco TC, Lietman TM, Doan T; MORDOR Study Group. Prolonged mass azithromycin distributions and macrolide resistance determinants among preschool children in Niger: A sub-study of a cluster-randomized trial (MORDOR). PLoS Med. 2024 May 6;21(5):e1004386. doi: 10.1371/journal.pmed.1004386. eCollection 2024 May.

  PMID: 38709718 DERIVED

• Chao DL, Arzika AM, Abdou A, Maliki R, Karamba A, Galo N, Beidi D, Harouna N, Abarchi M, Root E, Mishra A, Lebas E, Arnold BF, Oldenburg CE, Keenan JD, Lietman TM, O'Brien KS. Distance to Health Centers and Effectiveness of Azithromycin Mass Administration for Children in Niger: A Secondary Analysis of the MORDOR Cluster Randomized Trial. JAMA Netw Open. 2023 Dec 1;6(12):e2346840. doi: 10.1001/jamanetworkopen.2023.46840.

  PMID: 38100110 DERIVED

• 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.

  PMID: 34991704 DERIVED

• 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.

  PMID: 34037753 DERIVED

• 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.

  PMID: 33176084 DERIVED

• 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.

  PMID: 32931496 DERIVED

• 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.

  PMID: 32426812 DERIVED

• 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.

  PMID: 31981558 DERIVED

• 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.

  PMID: 31443654 DERIVED

• 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.

  PMID: 31167060 DERIVED

• 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.

  PMID: 31167050 DERIVED

• 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.

  PMID: 30561577 DERIVED

• 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.

  PMID: 29694816 DERIVED

• 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.

  PMID: 25858004 DERIVED

MeSH Terms

Conditions

Infections

Interventions

Azithromycin

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Ying Lin
• Organization: UCSF F.I. Proctor Foundation

ying.lin@ucsf.edu

4155144709

Study Officials

• Tom M Lietman, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Elodie J Lebas, RN

  University of California, San Francisco

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2014
• First Posted: January 29, 2014
• Study Start: December 1, 2014
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: November 8, 2022
• Results First Posted: January 3, 2020

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1); TA (1); GB (1); US (2); NI (1)