Vitality in Infants Via Azithromycin for Neonates Trial

NCT05763693 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 21-34232
• Study Type: interventional
• Target: 4,000
• Locations: 1 country
• Sites: 1

Brief Summary

Nearly half of child deaths occur during the neonatal period, and 80% of those occur in babies with low birthweight. Although tremendous progress has been made towards reducing under-five mortality globally, declines in neonatal mortality lag behind those observed in older children. Low birthweight babies are at increased risk of poor outcomes compared to those who are term-appropriate for gestational age, including mortality, stunting, and growth failure. Recent evidence has demonstrated that the incidence of wasting and linear growth failure is highest between birth and 3 months of age, substantially earlier than previously thought. Interventions are urgently needed to improve outcomes in low birthweight babies; however, these interventions must not interfere with breastfeeding and thus some well-established interventions used to treat or prevent malnutrition in older children cannot be considered. The investigators recently demonstrated that biannual mass azithromycin distribution reduces all-cause childhood mortality by approximately 25% in infants aged 1-5 months, with stronger effects seen in underweight infants. This study did not include neonates due to the risk of infantile hypertrophic pyloric stenosis (IHPS) that has been hypothesized to be associated with macrolide use during early infancy. However, our study team documented only a single case of IHPS among 21,833 neonates enrolled in a trial of azithromycin versus placebo administered to neonates aged 8-27 days for prevention of infant mortality, documenting no major risk of IHPS associated with azithromycin. Here, the investigators propose an individually randomized trial where participants will receive a single oral dose of azithromycin (administered either during the neontal period or 21 days after enrollment), two does of oral azithromycin spaced 21 days apart, or two doses of placebo to evalute if azithromycin improves nutritional outcome and reduces infectious burden among neonates aged 1-27 days who are either low birthweight (\<2500 g at birth) or underweight (weight-for-age Z-score \< -2 at enrollment). The primary outcome will be weight-for-age Z-score at 6 months of age compared between arms. The investigators anticipate that the results of this study will provide definitive evidence on azithromycin as an early intervention for low birthweight/underweight neonates, who are at the highest risk of adverse outcomes.

Conditions

Neonatal Death; Infectious Disease; Nutritional Deficiency

Keywords

Low birth weight; underweight neonates

Outcome Measures

Primary Outcomes (1)

• weight gain at 6 month of age

  Weight for Age Z score

  6 months

Secondary Outcomes (2)

• IHPS

  21 days

• Mortality at 6 months

  6 months

Study Arms (4)

Azithro-Azithro

ACTIVE COMPARATOR

A single oral dose of azithromycin (20 mg/kg) at baseline and a single oral dose of azithromycin (20 mg/kg) at the day 21 follow-up

Drug: Azithromycin at Baseline; Drug: Azithromycin at Day 21

Azithro-Placebo

ACTIVE COMPARATOR

A single oral dose of azithromycin (20 mg/kg) at baseline and a single oral dose of matching placebo at the day 21 follow-up

Drug: Azithromycin at Baseline; Other: Placebo at Day 21

Placebo-Azithro

ACTIVE COMPARATOR

A single oral dose of placebo at baseline and a single oral dose of azithromycin (20 mg/kg) at the day 21 follow-up

Drug: Azithromycin at Day 21; Other: Placebo at Baseline

Placebo-Placebo

PLACEBO COMPARATOR

A single oral dose of placebo at baseline and a single oral dose of matching placebo at the day 21 follow-up

Other: Placebo at Baseline; Other: Placebo at Day 21

Interventions

Azithromycin at Baseline DRUG

this group will be randomized to receive a single oral dose of azithromycin (20mg/kg) at baseline

Azithro-Azithro; Azithro-Placebo

Azithromycin at Day 21 DRUG

this group will be randomized to receive a single oral dose of azithromycin (20mg/kg) at the day 21 visit

Azithro-Azithro; Placebo-Azithro

Placebo at Baseline OTHER

this group will be randomized to receive Placebo at baseline

Placebo-Azithro; Placebo-Placebo

Placebo at Day 21 OTHER

This group will be randomized to receive Placebo at the day 21 visit

Azithro-Placebo; Placebo-Placebo

Eligibility Criteria

• Age: 1 Day - 27 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Aged 1-27 days old
• Birthweight \< 2500 g and/or weight-for-height Z score \<- 2 standard deviations at enrollment
• Weigh at least 1500 g at time of enrollment
• Able to feed orally
• Family intends to stay in the study area for at least 6 months
• Written informed consent from at least one caregiver
• Afebrile
• Caregiver at least 18 years old
• No known allergy to macrolides
• No hepatic failure manifested by neonatal jaundice
• Not currently an inpatient at the clinic
• Not being transferred to a hospital for clinical complications

You may not qualify if:

• Birthweight \> 2500 g
• Weigh less than 1500 g at time of enrollment
• Unable to feed orally
• Family planning to move within 6 months
• Mother/ caregiver not willing to participate
• Allergic to macrolides
• Hepatic failure manifested by neonatal jaundice
• Currently being seen as an inpatient at the clinic
• Currently being transferred to a hospital for clinical complications

Sponsors & Collaborators

• University of California, San Francisco: lead
• Centre de Recherche en Sante de Nouna, Burkina Faso: collaborator

Study Sites (1)

Centre de Recherche en santé de Nouna

Nouna, BP02, Burkina Faso

Location

MeSH Terms

Conditions

Perinatal Death; Communicable Diseases; Malnutrition

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections; Disease Attributes; Nutrition Disorders; Nutritional and Metabolic Diseases

Study Officials

• Catherine Oldenburg, ScD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elodie Lebas, RN

CONTACT

(415) 476-1442; elodie.lebas@ucsf.edu

Catherine Oldenburg, ScD

CONTACT

(415) 476-1442; catherine.oldenburg@ucsf.edu

Study Design

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

Study Record Dates

• First Submitted: February 24, 2023
• First Posted: March 10, 2023
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2030
• Last Updated: August 29, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1)