Neonatal Infection
Conditions
Brief summary
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.
Interventions
DIETARY_SUPPLEMENTZinc Supplements
Dispersible zinc citrate tablets
DIETARY_SUPPLEMENTPlacebo Supplements
Dispersible placebo tablets
Sponsors
Muhimbili University of Health and Allied Sciences
Harvard School of Public Health (HSPH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
0 Days to 59 Days
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Death | 90 Days | All-cause infant death |
| Treatment Failure | 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of signs of clinical severe infection | Randomization to Day 90 | Hours from randomization to the absence of any sign of clinical severe infection |
| Diarrhea during initial hospital admission | Randomization to the date of initial hospitalization discharge, assessed up to 90 days | Clinical diagnosis based on three or more loose or watery stools in the past 24 hours |
| Rate of vomiting related to regimen dosing | Randomization to Day 15 | Vomiting observed by study staff within 30 minutes of regimen dosing |
| Re-hospitalization | Date of initial hospitalization discharge to Day 90 | Infant admitted and stayed overnight in health facility after being discharged from initial hospitalization |
| Presence of any sign of possible severe bacterial infection at Day 15 | 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. |
| Presence of any sign of possible severe bacterial infection at Day 90 | 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. |
| Proportion of Children with Diarrhea at Day 15 or Day 90 | Day 15 and Day 90 | Maternal report of three or more loose or watery stools in the past 24 hours |
| Death during initial hospitalization | Randomization to the date of initial hospitalization discharge, assessed up to 90 days | All-cause mortality during initial hospitalization |
| Infant length-for-age z-score at Day 90 | Day 90 | Infant length-for-age z-score by WHO Child Growth Standards |
| Infant weight-for-age z-score at Day 15 | Day 15 | Infant weight-for-age z-score by WHO Child Growth Standards |
| Infant weight-for-age z-score at Day 90 | Day 90 | Infant weight-for-age z-score by WHO Child Growth Standards |
| Infant weight-for-length z-score at Day 15 | Day 15 | Infant weight-for-length z-score by WHO Child Growth Standards |
| Infant weight-for-length z-score at Day 90 | Day 90 | Infant weight-for-length z-score by WHO Child Growth Standard |
| Plasma zinc concentrations at Day 15 | Day 15 | Infant plasma zinc concentration |
| Infant length-for-age z-score at Day 15 | Day 15 | Infant length-for-age z-score by WHO Child Growth Standards |
| Duration of initial hospital stay | Randomization to Day 90 | Hours from randomization to initial hospitalization discharge |
Countries
Tanzania
Contacts
Primary ContactChristopher R Sudfeld, ScD
Outcome results
None listed