Effects of Mass Drug Administration of Azithromycin on Mortality and Other Outcomes Among 1-11 Month Old Infants in Mali

NCT04424511

Last updated date
Study Location
Center for Vaccine Development CVD-Mali
Bamako, , BP 251, Mali
Contact
407280345

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Mortality
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
0-364
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

On a cluster (village) level:

1. Location within Kayes, Kita, or Koulikoro region of Mali

2. Considered accessible and safe by the local health authorities and research team

3. Considered non-urban by the local health authorities and research team

4. Permission from community leadership

On a household level (for trial enrollment):

1. Location within a cluster that is included in the study

2. Verbal consent from a head of household or an adult authorized by her / him

On a child level (for receiving study medication):

1. Residence in a household enrolled in the trial

2. Age between 29 and 364 days

3. Verbal consent from at least one caregiver

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


On child level (for not receiving study medication):


1. Weight below 3.0 kg


2. Known allergy to macrolides, as judged by a caregiver report of the infant
experiencing an adverse reaction after oral ingestion of medication, which was deemed
likely to be a macrolide by the interviewing data collector.

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Advanced Information
Descriptive Information
Brief Title  ICMJE Effects of Mass Drug Administration of Azithromycin on Mortality and Other Outcomes Among 1-11 Month Old Infants in Mali
Official Title  ICMJE LAKANA , a Cluster-randomized, Double-blinded, Parallel Group, Controlled Trial, Testing the Effects of Mass Drug Administration of Azithromycin on Mortality and Other Outcomes Among 1-11 Month Old Infants in Rural Mali.
Brief Summary The LAKANA trial will assess the impact on mortality and other health outcomes of quarterly and biannual azithromycin mass drug administration (MDA) when delivered to 1-11-month old infants in a high-mortality setting where malaria is holoendemic but there is also a functioning seasonal malaria chemoprevention (SMC) program in place. The long-term goal is to more precisely define the role of mass azithromycin treatments as an intervention for reducing childhood mortality, and to determine the most effective treatment regimen. The main study hypotheses in terms of mortality effect are: i) Biannual azithromycin MDA to 1-11 month old infants reduces their mortality, ii) Quarterly azithromycin MDA to 1-11 month old infants reduces their mortality, iii) Quarterly azithromycin MDA has a bigger mortality effect than biannual MDA.
Detailed Description

Mass drug administration (MDA) of azithromycin has been shown to reduce under-5 mortality in some but not all sub-Saharan African settings. Because of the observed heterogeneity and possible effect modification by SMC or other co-interventions, further trials in new settings are needed in order to make evidence-based public health recommendations about the use of this treatment. The objectives of the LAKANA trial are:

  • To evaluate the impact of two azithromycin MDA regimens on infant mortality and other health outcomes, when provided in a rural West-African high-mortality context with an ongoing seasonal malaria chemoprevention program.
  • To evaluate the effect of alternative MDA frequencies on antimicrobial resistance (AMR) and host microbiota composition.
  • To test hypotheses that azithromycin MDA eliminates malaria parasitaemia and reduces systemic and intestinal inflammation in asymptomatic children and to collect and store biological samples for assessing other possible mechanisms of azithromycin effect.
  • To investigate the feasibility, acceptability and equity of alternative MDA strategies.

The LAKANA trial will be conducted in 830 villages from 7-10 health districts in the Kayes, Kita and Koulikoro regions of Mali. LAKANA is a cluster-randomized, placebo-controlled, double-blinded, parallel-group, three-arm clinical trial, with adaptive design. Participating villages will be randomly allocated to three different intervention groups in a ratio of 3 : 2 : 4 (control : azithromycin quarterly : azithromycin biannually). Within each participating village, consenting households will be visited quarterly (at 3-month intervals), nine times. At the first eight of these visits, 1-11-month-old eligible infants (age 29-364 days), for whom there is a consent for study drug provision, will be given a single dose of study drug (azithromycin mixture or respective placebo mixture).

Mortality data will be collected, and mortality-related questions primarily answered using data from approximately 770 villages (clusters) (primary outcome sample). Mixed-effect Poisson regression model will be used to estimate the intervention effects on mortality, with random intercepts for the clusters. The investigators will explore effect modification by testing for interaction between the MDA intervention and the following variables:

  • Infant age at the time of MDA (1-5 months vs 6-11 months)
  • Infant weight-for-age at the time of MDA
  • Infant sex
  • Season of MDA dosing and time since the last SMC
  • Cluster level coverage of SMC
  • Cluster level baseline mortality (established at first census)
  • Cluster and individual level coverage and number of administered azithromycin MDA doses
  • District of residence
  • Distance from the nearest health facility
  • Household asset or income index
  • Household WASH index

The investigators will address the other study questions using a smaller separate secondary sample of 60 villages located around four selected health centers close to the city of Kita and 20 villages around two health facilities in Koulikoro.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
LAKANA is a cluster-randomized, placebo-controlled, double-blinded, parallel-group, three-arm clinical trial, with adaptive design.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
The investigators will utilize a matching placebo to mask study arm allocation. All children aged 1-11 months in all study communities will be offered biannual or quarterly azithromycin or placebo distribution in an identical fashion. Placebo will be identical to azithromycin in appearance, taste, odor, and packaging. The interventions will be coded only with a letter code.
Primary Purpose: Treatment
Condition  ICMJE Mortality
Intervention  ICMJE
  • Drug: Placebo
    Placebo mixture will be administered as a single dose in oral suspension form for children 1-11 months of age. Weight-based dosing will be used: single-dose of 0.5 ml / kg child weight.
  • Drug: Azithromycin
    Azithromycin will be administered as a single dose in oral suspension form for children 1-11 months of age. Weight-based dosing will be used: single-dose of 0.5 ml (20 mg) / kg child weight.
Study Arms  ICMJE
  • Placebo Comparator: Control

    Placebo mixture will be administered as a single dose in oral suspension form for children 1-11 months of age:

    1. Single-dose of 0.5 ml / kg child weight
    2. Participating households within villages allocated to this group will be visited quarterly (at 3-month intervals), for nine times. At the first eight of these visits, 1-11 month old eligible infants, for whom there is a consent for study drug provision, will be weighed and given a single dose of placebo mixture.
    Intervention: Drug: Placebo
  • Active Comparator: Azithromycin-biannually (Azi-biannual)

    Azithromycin or placebo will be administered as a single dose in oral suspension form for children 1-11 months of age:

    1. Single-dose of 0.5 ml / kg child weight
    2. Participating households within villages allocated to this group will be visited quarterly (at 3-month intervals), for nine times. At the first eight of these visits, 1-11 month old eligible infants, for whom there is a consent for study drug provision, will be weighed and given a single dose of study drug.
    3. Azithromycin will be given at quarterly visits between January and June, and Placebo mixture will be given at quarterly visits between July and December. Azithromycin dose will be 20 mg / kg.
    Interventions:
    • Drug: Placebo
    • Drug: Azithromycin
  • Active Comparator: Azithromycin-quarterly

    Azithromycin will be administered as a single dose in oral suspension form for children 1-11 months of age:

    1. Single-dose of 0.5 ml (20 mg) / kg child weight.
    2. Participating households within villages allocated to this group will be visited quarterly (at 3-month intervals), for nine times. At the first eight of these visits, 1-11 month old eligible infants, for whom there is a consent for study drug provision, will be weighed and given a single dose of azithromycin.
    Intervention: Drug: Azithromycin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 5, 2020)
100000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

On a cluster (village) level:

  1. Location within Kayes, Kita, or Koulikoro region of Mali
  2. Considered accessible and safe by the local health authorities and research team
  3. Considered non-urban by the local health authorities and research team
  4. Permission from community leadership

On a household level (for trial enrollment):

  1. Location within a cluster that is included in the study
  2. Verbal consent from a head of household or an adult authorized by her / him

On a child level (for receiving study medication):

  1. Residence in a household enrolled in the trial
  2. Age between 29 and 364 days
  3. Verbal consent from at least one caregiver

Exclusion Criteria:

On child level (for not receiving study medication):

  1. Weight below 3.0 kg
  2. Known allergy to macrolides, as judged by a caregiver report of the infant experiencing an adverse reaction after oral ingestion of medication, which was deemed likely to be a macrolide by the interviewing data collector.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE up to 364 Days   (Child)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Per Ashorn, MD, PhD407280345 ext +358[email protected]
Contact: Ulla Ashorn, PhD407080354 ext +358[email protected]
Listed Location Countries  ICMJE Mali
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04424511
Other Study ID Numbers  ICMJE LAKANA trial
INV-003354 ( Other Grant/Funding Number: Bill and Melinda Gates Foundation )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:Yes
Plan Description:Individual participant data collected during the trial, after deidentification. (The details are to be determined).
Supporting Materials:Study Protocol
Supporting Materials:Statistical Analysis Plan (SAP)
Supporting Materials:Informed Consent Form (ICF)
Supporting Materials:Clinical Study Report (CSR)
Time Frame:Starting 6 months after publication
Access Criteria:(The details are to be determined)
Responsible Party Per Ashorn, Tampere University
Study Sponsor  ICMJE Tampere University
Collaborators  ICMJE
  • Center for Vaccine Development CVD-Mali, Bamako, Mali
  • University College London, UK.
  • Tro Da Ltd, UK
  • Duke-NUS Graduate Medical School
  • Bill and Melinda Gates Foundation (Funder)
  • Pfizer Inc. (Provider of study drugs)
Investigators  ICMJE
Principal Investigator:Per Ashorn, MD, PhDCenter for Child Health Research, Tampere University
Principal Investigator:Ulla Ashorn, PhDCenter for Child Health Research, Tampere University
Principal Investigator:Samba Sow, MD, MScCenter for Vaccine Development CVD-Mali
Principal Investigator:Nigel Klein, MBBS, PhDUniversity College London, UK.
Principal Investigator:Camilla Ducker, MBBS, MScTro Da Ltd, UK
Principal Investigator:Yin Bun Cheung, PhDCentre for Quantitative Medicine, Duke-NUS Medical School
PRS Account Tampere University
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP