Zinc Supplementation for Young Infants With Clinical Severe Infection in Tanzania

Trial of Zinc Supplements for Young Infants With Clinical Severe Infection in Tanzania

Bacterial infections among young infants, including sepsis, meningitis, and pneumonia, continue to cause a substantial number of deaths globally. Zinc supplementation in combination with standard antibiotic therapy may represent a new intervention to reduce mortality and improve treatment outcomes for young infants with clinical severe infection.

The Investigators will conduct a randomized, double-blind, placebo-controlled trial of zinc supplementation among young infants 0-59 days with severe clinical infection. The trial will enroll 3,250 Tanzanian infants hospitalized with clinical severe infection as defined by WHO Integrated Management of Childhood Illness (IMCI) guidelines. Enrolled infants will receive standard clinical management including antibiotics and will be randomized to receive either a 14-day course of twice-daily 5 mg elemental zinc (10 mg per day) or a matching placebo regimen.

Study Overview

• Status: Recruiting
• Conditions: Neonatal Infection
• Intervention / Treatment: Dietary supplement: Placebo Supplements; Dietary supplement: Zinc Supplements

• Study Type: Interventional
• Enrollment (Estimated): 3250
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Christopher R Sudfeld, ScD; Phone Number: (617) 432-5051; Email: csudfeld@hsph.harvard.edu

Study Locations

• Tanzania
  • Dar es Salaam, Tanzania
    • Recruiting
    • Muhimbili University of Health and Allied Sciences
    • Contact: Karim P Manji, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Young infants aged 0-59 days
• Diagnosis of clinical severe infection (CSI)
• Ability to feed enterally
• Intend to stay in the study area for 90 days
• Provided informed consent

Exclusion Criteria:

• Prior use of zinc supplements during the current illness
• Receipt of antibiotics for >24 hours before enrollment
• Diarrhea at enrollment
• Signs suggestive of serious illness/condition that is not clinical severe infection
• Previously enrolled in the trial
• Enrolled in other research study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zinc Supplementation; 14-day regimen of twice-daily 5 mg elemental zinc supplements to be taken orally or by enteral feeding tube	Dietary supplement: Zinc Supplements; Dispersible zinc citrate tablets
Placebo Comparator: Placebo; 14-day regimen of twice-daily oral placebo supplements to be taken orally or by enteral feeding tube	Dietary supplement: Placebo Supplements; Dispersible placebo tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death	All-cause infant death	90 Days
Treatment Failure	A composite endpoint of death during initial period of hospitalization, the need for additional respiratory support (either mechanical ventilation, or positive end expiratory pressure support) or the use of vasoactive medicines to support blood pressure or need to change antibiotics during the initial hospitalization	From date of randomization until the date of first documented treatment failure or date of death from any cause during the initial hospitalization, whichever comes first, assessed up to 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death during initial hospitalization	All-cause mortality during initial hospitalization	Randomization to the date of initial hospitalization discharge, assessed up to 90 days
Duration of initial hospital stay	Hours from randomization to initial hospitalization discharge	Randomization to Day 90
Duration of signs of clinical severe infection	Hours from randomization to the absence of any sign of clinical severe infection	Randomization to Day 90
Diarrhea during initial hospital admission	Clinical diagnosis based on three or more loose or watery stools in the past 24 hours	Randomization to the date of initial hospitalization discharge, assessed up to 90 days
Rate of vomiting related to regimen dosing	Vomiting observed by study staff within 30 minutes of regimen dosing	Randomization to Day 15
Re-hospitalization	Infant admitted and stayed overnight in health facility after being discharged from initial hospitalization	Date of initial hospitalization discharge to Day 90
Presence of any sign of possible severe bacterial infection at Day 15	Presence of a clinical sign of possible severe bacterial infection, including: high body temperature ≥38°C, low body temperature <35.5°C , severe chest indrawing, movement only on stimulation or no movement at all, stopped feeding well or unable to feed at all, or convulsions.	Day 15
Presence of any sign of possible severe bacterial infection at Day 90	Presence of a clinical sign of possible severe bacterial infection, including: high body temperature ≥38°C, low body temperature <35.5°C , severe chest indrawing, movement only on stimulation or no movement at all, stopped feeding well or unable to feed at all, or convulsions.	Day 90
Proportion of Children with Diarrhea at Day 15 or Day 90	Maternal report of three or more loose or watery stools in the past 24 hours	Day 15 and Day 90
Infant length-for-age z-score at Day 15	Infant length-for-age z-score by WHO Child Growth Standards	Day 15
Infant length-for-age z-score at Day 90	Infant length-for-age z-score by WHO Child Growth Standards	Day 90
Infant weight-for-age z-score at Day 15	Infant weight-for-age z-score by WHO Child Growth Standards	Day 15
Infant weight-for-age z-score at Day 90	Infant weight-for-age z-score by WHO Child Growth Standards	Day 90
Infant weight-for-length z-score at Day 15	Infant weight-for-length z-score by WHO Child Growth Standards	Day 15
Infant weight-for-length z-score at Day 90	Infant weight-for-length z-score by WHO Child Growth Standard	Day 90
Plasma zinc concentrations at Day 15	Infant plasma zinc concentration	Day 15

Collaborators and Investigators

• Sponsor: Harvard School of Public Health (HSPH)
• Collaborators: Muhimbili University of Health and Allied Sciences
• Investigators: Principal Investigator: Christopher R Sudfeld, ScD, Harvard School of Public Health (HSPH); Principal Investigator: Christopher P Duggan, MD, Harvard School of Public Health (HSPH) and Boston Children's Hospital; Principal Investigator: Karim P Manji, MD, Muhimbili University of Health and Allied Sciences

Publications and helpful links

General Publications

• Manji KP, Somji S, Bakari M, Fawzi WW, Kibwana U, Kisenge R, Kisumuni AS, Liu E, Mafie N, Maleko FA, Salim N, Duggan CP, Sudfeld CR. Efficacy of zinc supplementation for young infants with clinical severe infection in Tanzania: study protocol for a randomised controlled trial. BMJ Paediatr Open. 2025 Aug 14;9(1):e003804. doi: 10.1136/bmjpo-2025-003804.

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2024
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2027

Study Registration Dates

• First Submitted: October 20, 2023
• First Submitted That Met QC Criteria: October 25, 2023
• First Posted (Actual): October 26, 2023

Study Record Updates

• Last Update Posted (Actual): December 12, 2025
• Last Update Submitted That Met QC Criteria: December 5, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: IRB23-0138

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• 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