MORDORIIMortY5: Mortality Reduction After Oral Azithromycin Contingency: Mortality Study

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT03338244
• Collaborator: The Carter Center (Other), Bill and Melinda Gates Foundation (Other)
• Enrollment: 66,228
• Locations: 2
• Arms: 2
• Actual Duration (Months): 33.3
• Patients Per Site: 33114
• Patients Per Site Per Month: 993

Study Details

Study Description

Brief Summary

MORDOR was a cluster-randomized placebo controlled trial that assessed the efficacy of mass azithromycin distributions for the prevention of childhood mortality. All communities were subsequently treated with mass azithromycin for one year. The present trial re-randomized communities to azithromycin or placebo for the fourth and fifth year of the study.

Condition or Disease	Intervention/Treatment	Phase
Childhood Mortality	Drug: Azithromycin; Drug: Placebo	Phase 4

Detailed Description

Pre-trial treatments: in the original MORDOR trial, communities were randomized to 4 rounds of biannual mass distributions of either azithromycin or placebo (i.e, the first two years of the trial). All communities were subsequently treated with 2 rounds of biannual mass azithromycin (i.e., the fifth and sixth rounds, during the third year of the trial).

Present trial design: The present trial enrolls all communities previously enrolled in the Niger site of MORDOR, and re-randomizes communities to biannual mass distributions of either azithromycin or placebo (i.e., the seventh, eighth, ninth and tenth rounds of mass drug administration since randomization for the original MORDOR trial, occurring in the fourth and fifth year since randomization). This results in four patterns of community-based treatment: four years of azithromycin (AAAAA), three years of azithromycin followed by one year of placebo (AAAPP), two years of placebo followed by two years of azithromycin (PPAAA), and two years of placebo followed by one year of azithromycin and then one year of placebo (PPAPP). The primary outcome will be all-cause mortality in children aged 1-59 months,as determined by biannual census. The mortality rate following re-randomization (i.e., the seventh, eighth, ninth and tenth rounds of mass drug administration) will be compared between the two re-randomized groups.

Study Design

• Study Type: Interventional
• Actual Enrollment: 66228 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Mortality Reduction After Oral Azithromycin Contingency: Mortality Study
• Actual Study Start Date: Oct 20, 2017
• Actual Primary Completion Date: Jul 31, 2020
• Actual Study Completion Date: Jul 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Azithro Communities will receive four rounds of biannual mass azithromycin.	Drug: Azithromycin; Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months; Other Names: Zithromax
Placebo Comparator: Placebo Communities will receive four rounds of biannual mass placebo.	Drug: Placebo; Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo suspension every 6 months

Outcome Measures

Primary Outcome Measures

1. All-cause Mortality Rate in Children Aged 1-60 Months [24 months]

   as measured by presence on census and absence on sequential census due to death

2. Macrolide Resistance in Children Aged 1-60 Months [18 months]

   as measured by nasopharyngeal swabs

3. Normalized Macrolide Resistance in Children Aged 1-60 Months [18 months]

   as measured by rectal swabs. Fraction of macrolide resistance from stool specimens in children 1-60 months (core). For Niger, this includes RNA, DNA, and TAC-card methods (a binary outcome at the individual level).

Secondary Outcome Measures

1. Microbial Composition of Stool [18 months]

   as measured by Meta-genomic Deep Sequencing

2. Campylobacter and Other Pathogenic Organisms in Stool [18 months]

   as measured by molecular techniques

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Month to 60 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Communities- All communities eligible for MORDOR (NCT02047981)

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

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Proctor Foundation	San Francisco	California	United States	94143-0944
2	The Carter Center	Niamey		Niger

Sponsors and Collaborators

• University of California, San Francisco
• The Carter Center
• Bill and Melinda Gates Foundation

Investigators

• Principal Investigator: Tom M Lietman, MD, UCSF Proctor Foundation
• Study Director: Elodie Lebas, RN, UCSF Proctor Foundation

Study Documents (Full-Text)

• Study Protocol - Oct 1, 2019
• Statistical Analysis Plan - Nov 1, 2020

More Information

Publications

None provided.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT03338244
• Other Study ID Numbers: 10-01036-Y4; OPP1032340-A
• First Posted: Nov 9, 2017
• Last Update Posted: Aug 11, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by University of California, San Francisco: Childhood mortality; Mass treatment; Azithromycin; Infection
• Additional relevant MeSH terms: Azithromycin

Study Results

Participant Flow

Arm/Group Title	Azithro	Placebo
Arm/Group Description	Communities will receive four rounds of biannual mass azithromycin. Azithromycin: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months	Communities will receive four rounds of biannual mass placebo. Placebo: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo suspension every 6 months
Period Title: Overall Study
STARTED	33173	33055
COMPLETED	25995	25568
NOT COMPLETED	7178	7487

Baseline Characteristics

Arm/Group Title	Azithro	Placebo	Total
Arm/Group Description	Communities will receive four rounds of biannual mass azithromycin. Azithromycin: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months	Communities will receive four rounds of biannual mass placebo. Placebo: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo suspension every 6 months	Total of all reporting groups
Overall Participants	33173	33055	66228
Age (Count of Participants)
<=18 years	33173 100%	33055 100%	66228 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	16052 48.4%	16084 48.7%	32136 48.5%
Male	17121 51.6%	16971 51.3%	34092 51.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	33173 100%	33055 100%	66228 100%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Niger	33173 100%	33055 100%	66228 100%

Outcome Measures

1. Primary Outcome

Title	All-cause Mortality Rate in Children Aged 1-60 Months
Description	as measured by presence on census and absence on sequential census due to death
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Number of participants at the start of MORDOR III

Arm/Group Title	Azithro	Placebo
Arm/Group Description	Communities will receive four rounds of biannual mass azithromycin. Azithromycin: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months	Communities will receive four rounds of biannual mass placebo. Placebo: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo suspension every 6 months
Measure Participants	33173	33055
Number (95% Confidence Interval) [deaths per 1000 person years]	24.8	26.7

2. Primary Outcome

Title	Macrolide Resistance in Children Aged 1-60 Months
Description	as measured by nasopharyngeal swabs
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

We did collect nasopharyngeal swabs but pooling and DNA-seq that works with rectal samples was not sensitive enough for NP samples. So we have to wait for technology to catch up to be able to report these results.

Arm/Group Title	Azithro	Placebo
Arm/Group Description	Communities will receive four rounds of biannual mass azithromycin. Azithromycin: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months	Communities will receive four rounds of biannual mass placebo. Placebo: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo suspension every 6 months
Measure Participants	0	0

3. Primary Outcome

Title	Normalized Macrolide Resistance in Children Aged 1-60 Months
Description	as measured by rectal swabs. Fraction of macrolide resistance from stool specimens in children 1-60 months (core). For Niger, this includes RNA, DNA, and TAC-card methods (a binary outcome at the individual level).
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

1,004 children in total (557 from 15 placebo-treated communities and 447 from 14 azithromycin-treated communities).

Arm/Group Title	Azithro	Placebo
Arm/Group Description	Communities will receive four rounds of biannual mass azithromycin. Azithromycin: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months	Communities will receive four rounds of biannual mass placebo. Placebo: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo suspension every 6 months
Measure Participants	447	557
Mean (95% Confidence Interval) [reads per million (rM)]	79.85	15.79

4. Secondary Outcome

Title	Microbial Composition of Stool
Description	as measured by Meta-genomic Deep Sequencing
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

Unfortunately, we didn't collect stool, so we won't be able to report this.

Arm/Group Title	Azithro	Placebo
Arm/Group Description	Communities will receive four rounds of biannual mass azithromycin. Azithromycin: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months	Communities will receive four rounds of biannual mass placebo. Placebo: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo suspension every 6 months
Measure Participants	0	0

5. Secondary Outcome

Title	Campylobacter and Other Pathogenic Organisms in Stool
Description	as measured by molecular techniques
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

Unfortunately, we didn't collect stool, so we won't be able to report this.

Arm/Group Title	Azithro	Placebo
Arm/Group Description	Communities will receive four rounds of biannual mass azithromycin. Azithromycin: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months	Communities will receive four rounds of biannual mass placebo. Placebo: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo suspension every 6 months
Measure Participants	0	0

Adverse Events

Time Frame	2 years
Adverse Event Reporting Description	No adverse events were reported other than death
Arm/Group Title	Azithro		Placebo
Arm/Group Description	Communities will receive four rounds of biannual mass azithromycin. Azithromycin: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral azithromycin suspension every 6 months		Communities will receive four rounds of biannual mass placebo. Placebo: Children aged 1 month to 60 months per community will be offered weight or height-based, directly observed, oral placebo suspension every 6 months
All Cause Mortality
	Azithro		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1493/33173 (4.5%)		1584/33055 (4.8%)
Serious Adverse Events
	Azithro		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33173 (0%)		0/33055 (0%)
Other (Not Including Serious) Adverse Events
	Azithro		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33173 (0%)		0/33055 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.