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Trial record 95 of 185 for:    ERYTHROMYCIN

Neonates and Azithromycin, an Innovation in the Treatment of Children in Burkina Faso (NAITRE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03682653
Recruitment Status : Recruiting
First Posted : September 24, 2018
Last Update Posted : April 22, 2019
Sponsor:
Collaborators:
Centre de Recherche en Sante de Nouna, Burkina Faso
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE September 19, 2018
First Posted Date  ICMJE September 24, 2018
Last Update Posted Date April 22, 2019
Actual Study Start Date  ICMJE April 11, 2019
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 21, 2018)
6 month mortality - all cause [ Time Frame: 6 months ]
All-cause Mortality Rate in infants at 6 months of age
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03682653 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 19, 2019)
  • 12 month mortality - all cause [ Time Frame: 12 months ]
    All-cause Mortality Rate in infants at 12 months of age
  • Vital Status [ Time Frame: 12 months ]
    Caregivers will be asked if the child is dead or alive at 365 days of life
  • Change in weight over time [ Time Frame: 6 months ]
    Change in weight from baseline to day 180
  • Change in height over time [ Time Frame: 6 months ]
    Change in height from baseline to day 180
  • Proportion of infants developing infantile hypertrophic pyloric stenosis [ Time Frame: 8 weeks ]
    Proportion of infants developing infantile hypertrophic pyloric stenosis between 2 to 8 weeks after treatment
  • Adverse events [ Time Frame: 12 months ]
    Caregivers will be asked if their child experienced any symptoms for pyloric stenosis since the last visit.
  • Neonatal Mortality [ Time Frame: 28 days ]
    Mortality prior to 28 days of life
Original Secondary Outcome Measures  ICMJE
 (submitted: September 21, 2018)
  • 12 month mortality - all cause [ Time Frame: 12 months ]
    All-cause Mortality Rate in infants at 12 months of age
  • Vital Status [ Time Frame: 1 week ]
    Vital Status will be measured by questionnaire. The caregiver will tell the investigators if the child is dead or alive at 1 week post-treatment
  • Vital Status [ Time Frame: 2 weeks ]
    Vital Status will be measured by questionnaire. The caregiver will tell the investigators if the child is dead or alive at 2 weeks post-treatment
  • Vital Status [ Time Frame: 3 weeks ]
    Vital Status will be measured by questionnaire. The caregiver will tell the investigators if the child is dead or alive at 3 weeks post-treatment
  • Vital Status [ Time Frame: 90 days ]
    Vital Status will be measured by questionnaire. The caregiver will tell the investigators if the child is dead or alive at 90 days of life
  • Vital Status [ Time Frame: 180 days ]
    Vital Status will be measured by questionnaire. The caregiver will tell the investigators if the child is dead or alive at 180 days of life
  • Vital Status [ Time Frame: 12 months ]
    Vital Status will be measured by questionnaire. The caregiver will tell the investigators if the child is dead or alive at 365 days of life
  • Change in weight over time [ Time Frame: 6 months ]
    Change in weight from baseline to day 180
  • Change in height over time [ Time Frame: 6 months ]
    Change in height from baseline to day 180
  • Proportion of infants developing infantile hypertrophic pyloric stenosis [ Time Frame: 8 weeks ]
    Proportion of infants developing infantile hypertrophic pyloric stenosis between 2 to 8 weeks after treatment
  • Adverse events [ Time Frame: 12 months ]
    Caregivers will be asked if their child experienced any symptoms for pyloric stenosis since the last visit.
  • Intestinal microbial diversity at day 0 [ Time Frame: day 0 ]
    Simpson's diversity estimated from next generation sequencing at day 0
  • Intestinal microbial diversity at day 14 [ Time Frame: day 14 ]
    Simpson's diversity estimated from next generation sequencing at day 14
  • Intestinal microbial diversity at day 180 [ Time Frame: day 180 ]
    Simpson's diversity estimated from next generation sequencing at day 180
  • Intestinal microbial diversity at day 0 [ Time Frame: day 0 ]
    Shannon's diversity estimated from next generation sequencing at day 0
  • Intestinal microbial diversity at day 14 [ Time Frame: day 14 ]
    Shannon's diversity estimated from next generation sequencing at day 14
  • Intestinal microbial diversity at Day 180 [ Time Frame: day 180 ]
    Shannon's diversity estimated from next generation sequencing at Day 180
  • Nasopharyngeal microbial diversity at Day 0 [ Time Frame: Day 0 ]
    Shannon's diversity estimated from next generation sequencing
  • Nasopharyngeal microbial diversity at Day 14 [ Time Frame: Day 14 ]
    Shannon's diversity estimated from next generation sequencing at Day 14
  • Nasopharyngeal microbial diversity at Day 180 [ Time Frame: Day 180 ]
    Shannon's diversity estimated from next generation sequencing at Day 180
  • Nasopharyngeal microbial diversity at Day 0 [ Time Frame: Day 0 ]
    Simpson's diversity estimated from next generation sequencing at Day 0
  • Nasopharyngeal microbial diversity at Day 14 [ Time Frame: Day 14 ]
    Simpson's diversity estimated from next generation sequencing at Day 14
  • Nasopharyngeal microbial diversity at Day 180 [ Time Frame: Day 180 ]
    Simpson's diversity estimated from next generation sequencing at Day 180
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neonates and Azithromycin, an Innovation in the Treatment of Children in Burkina Faso
Official Title  ICMJE Neonates and Azithromycin, an Innovation in the Treatment of Children in Burkina Faso
Brief Summary

Although under-5 mortality rates are declining globally, neonatal mortality remains persistently high in many regions of sub-Saharan Africa. Mass azithromycin distribution to children aged 1-59 months has been shown to reduce childhood mortality in Niger, Tanzania, and Malawi. This study did not evaluate the effect of azithromycin administered during the neonatal period. Observational evidence from high income countries has suggested that macrolides, including erythromycin and azithromycin, may be associated with increased risk of development of infantile hypertrophic pyloric stenosis (IHPS). However, these studies are limited by confounding by indication, as infants only receive antibiotics when they are ill.

The investigators proposed an individually randomized trial of azithromycin versus placebo to establish the efficacy and safety of administration of a dose of azithromycin during the neonatal period. The long-term goal is generate evidence that can be used by neonatal and child survival programs related to the use of azithromycin in the youngest children who have the highest risk of mortality. The investigators hypothesize that a single dose of azithromycin administered in the neonatal period will lead to significantly reduced risk of mortality and that this dose will be safe.

Objectives

  1. Establish the efficacy of a single dose of azithromycin administered during the neonatal period compared to placebo in infants 8 to 27 days of life for reduction in all-cause mortality.
  2. Establish the safety of a single dose of azithromycin administered during the neonatal period.

This study will be conducted in several regions of Burkina Faso, including peri-urban areas of Ouagadougou and Nouna town, and rural areas that are within 4 hours' drive of a pediatric facility with capacity for performing pyloromyotomy

Detailed Description

Child mortality in West Africa is among the highest in the world. Although child health and mortality are improving worldwide, children in the Sahel and sub-Sahel regions of West Africa have the greatest risks of mortality. Burkina Faso's current under-5 mortality rate is estimated 110 per 1,000 live births. Similar to other countries in the region, the major causes of child mortality in Burkina Faso are malaria, respiratory tract infection, and diarrhea. Malnutrition acts as a major underlying contributor to mortality. Neonatal mortality remains persistently high, with approximately 1/5th of neonatal mortality due to pneumonia, meningitis, and sepsis. Interventions that address these underlying causes may be particularly efficacious for reducing mortality.

Younger children at are at a higher risk of mortality. Approximately 2/3rd of under-5 deaths occur during the first year of life. In general, the child mortality rate decreases as age increases. While some improvement has been observed, neonatal mortality is declining at a slower rate than post-neonatal childhood mortality. Many child health interventions are designed specifically for children over 6 months of age, such as vitamin A supplementation, seasonal malaria chemoprevention, and lipid-based nutritional supplementation. Identification of strategies that are safe and effective for the youngest children will be required to address persistently high rates of neonatal and infant mortality.

The MORDOR I study demonstrated a significant reduction in all-cause child mortality following biannual mass azithromycin distribution. Across three diverse geographic locations in sub-Saharan Africa (Malawi, Niger, and Tanzania), biannual mass azithromycin distribution over a two-year period led to a 14% decrease in all-cause child mortality. In Niger, 1 in 5-6 deaths were averted. These results are qualitatively similar to those of a previous study of mass azithromycin distribution for trachoma control in Ethiopia, which found reduced odds of all-cause mortality in children in communities receiving mass azithromycin compared to control communities.

In MORDOR I, the strongest effect of azithromycin was in the youngest cohort of children. Across all three countries, the strongest effect of azithromycin was consistently in children 1-5 months of age, with an approximately 25% reduction in all-cause mortality. However, MORDOR I was not optimized to target the youngest age groups. Although children as young as 1 month were eligible, biannual distributions might not reach some children until 7 months of age. On average, children were first treated at 4 months. Given that there may be a substantial benefit to treating children at younger ages, azithromycin strategies that are designed to target younger age groups may be even more beneficial for reducing child mortality.

Here, the investigators propose a randomized controlled trial designed to evaluate the efficacy of a dose of azithromycin administered during the neonatal period for prevention of mortality within in the first 6 months of life. The investigators propose to randomize births in several geographic regions of Burkina Faso to a single dose of azithromycin or placebo between day 8 and 27 of life. This study is designed to provide evidence of the efficacy of azithromycin treatment for the youngest children.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
individually randomized trial of azithromycin versus placebo to establish the efficacy and safety of administration of a dose of azithromycin during the neonatal period
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Childhood Mortality
Intervention  ICMJE
  • Drug: Azithromycin
    a single dose of Azithromycin will be administered to infants between their 8-27th days of life
  • Drug: Placebo
    a single dose of Placebo will be administered to infants between their 8-27th days of life
Study Arms  ICMJE
  • Active Comparator: Azithromycin
    a single dose of Azithromycin will be administered to infants between their 8-27th days of life
    Intervention: Drug: Azithromycin
  • Placebo Comparator: Placebo
    a single dose of placebo will be administered to infants between their 8-27th days of life
    Intervention: Drug: Placebo
Publications * Sie A, Bountogo M, Nebie E, Ouattara M, Coulibaly B, Bagagnan C, Zabre P, Lebas E, Brogdon J, Godwin WW, Lin Y, Porco T, Doan T, Lietman TM, Oldenburg CE; NAITRE Study Group. Neonatal azithromycin administration to prevent infant mortality: study protocol for a randomised controlled trial. BMJ Open. 2019 Sep 4;9(9):e031162. doi: 10.1136/bmjopen-2019-031162.

*   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: September 21, 2018)
22000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2022
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Communities

Inclusion Criteria:

  • Within 4 hours of a facility that can provide services for pyloromyotomy (Ouagadougou or Bobo Dioulasso)
  • Accessible during the rainy season
  • Ultrasound machine available OR a facility in which an ultrasound machine could be placed is within 1 hour

Exclusion Criteria:

  • Refusal of village chief

Individuals:

Inclusion Criteria:

  • Weight over 2500 g
  • Able to feed orally
  • Family intends to stay in study area for at least 6 months
  • Appropriate consent from at least one caregiver
  • No known allergy to azalides
  • Not living within one of the communities included in the community study(CHAT/CHATON)
  • No hepatic failure manifested by neonatal jaundice

Exclusion Criteria:

  • Weight <2500 g
  • Unable to feed orally
  • Family planning to move
  • Mother/caregiver not willing to participate
  • Allergic to azalides
  • Living in one of the communities included in the community study (CHAT/CHATON)
  • Hepatic failure manifested by neonatal jaundice
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 27 Days   (Child)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Tom M Lietman, MD 415-502-2662 tom.lietman@ucsf.edu
Contact: Elodie J Lebas, RN 415-502-3192 elodie.lebas@ucsf.edu
Listed Location Countries  ICMJE Burkina Faso
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03682653
Other Study ID Numbers  ICMJE OPP1187628-B
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified data will be available as per the Bill and Melinda Gates open access policy. Individual participant data will be available that underline the reported results (texts, tables, figures, and appendices). The study protocol and statistical analysis plan will also be made available. The data will be available following publication in accordance with the BMGF guidelines.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: The data will be available following publication, without any embargo period.
Responsible Party University of California, San Francisco
Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE
  • Centre de Recherche en Sante de Nouna, Burkina Faso
  • Bill and Melinda Gates Foundation
Investigators  ICMJE
Principal Investigator: Catherine E Oldenburg, PhD University of California, San Francisco
Principal Investigator: Tom M Lietman, MD University of California, San Francisco
Principal Investigator: Ali Sie, MD, PhD Centre de Recherche en Sante de Nouna, Burkina Faso
PRS Account University of California, San Francisco
Verification Date April 2019

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