Therapeutic Zinc in Infant Bacterial Illness

• Status: Completed
• Trial end date: 2008-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Infections are the important cause of high mortality in young infants in developing countries. Zinc is a crucial micronutrient as it influences various immune mechanisms and modulates host resistance to several pathogens. It has shown benefits as an adjunct therapy in infections like diarrhea and pneumonia in older children Given the predisposition of young infants in developing countries to zinc deficiency and infections, addition of zinc to standard treatment of serious bacterial infections may lead to significant improvements in the outcomes.

Several hypotheses will be examined in this clinical trial. The primary objective is to measure, in a double blind randomized controlled trial, the efficacy of giving 2 RDA (Required Daily Allowance 10 mg) of zinc orally in addition to routine antibiotics, for treatment of possible serious bacterial infection in infants >= 7 days and up to 4 months of age in reducing the proportion of treatment failures and time to discharge from the hospital. This will evaluate the clinical consequences of the possible immunomodulation by zinc supplementation. This is critical to demonstrate because nearly 80% of infant mortality occurs in first months of life.

Young infants with possible serious bacterial infections fulfilling the inclusion criteria will be enrolled in the study and stratified into 4 groups on basis of weight for age 'z' scores < -2 z and >=- 2 z and whether he/she has diarrhea or not. Within each stratum the subjects will be randomized to receive zinc or placebo. Treatment failures will be defined by the need for a change of initial antibiotic therapy. The minimum duration of monitoring will be till clinical recovery (using predetermined criteria). Serum copper, serum ferritin and serum transferrin receptors will be determined at enrollment, 72 hours after enrollment and at discharge from the hospital. Concentrations of CRP and procalcitonin will be measured at baseline, 72 hours after enrolment and at clinical recovery.

Documentation of efficacy of addition of zinc to standard therapy may provide a simple and low-cost strategy to improve survival in serious infections in young infants. This is likely to have a significant impact on infant morbidity and mortality. It will be good example of using a simple immunomodulator beneficially in improving child health.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centre For International Health
• Collaborator: All India Institute of Medical Sciences, New Delhi
• Treatments: Zinc; Zinc Sulfate

Criteria

Inclusion Criteria:

Evidence of possible serious bacterial infection, defined as a CRP >= 12 mg/L and any one of the following clinical features:

Fever (axillary temperature >= 37.5 degrees C) or hypothermia (axillary temperature <35.5 degrees C).

Lethargic or unconscious. No attachment to the breast in breast fed infants. No suckling in breast fed infants. Convulsions in the present episode. Bulging fontanel.

• History of acute refusal of feed in the present episode.

• Acute history of excessive cry or irritability in the present episode.

• Fast breathing defined as >= 60 breaths/minute (on second count) for infants < 2 months and >= 50 breaths/min in infants 2 months up to 4 months.

• Grunting in the absence of any non infective cause.

• Cyanosis in the absence of any non infective cause.

• Severe chest in drawing.

• Unexplained shock.

• Diarrhea in present episode.

Exclusion Criteria:

• Congenital malformations e.g. hydrocephalus, structural CNS malformation.

• Severe birth asphyxia defined as:

• One minute APGAR (if available) of < 4/10.

• CT scan or MRI or EEG abnormalities if available suggestive of hypoxic ischemic encephalopathy.

• Known structural defects, which interfere with feeding, e.g.cleft palate esophageal abnormalities, intestinal atresia and stenosis, malrotation of the gut,anorectal malformation.

• Subjects requiring ventilation or ionotropic support.

• History of diarrhea in the present episode.

• Known inborn error of metabolism.

• Chronic disorders of other organs e.g. neonatal cholestasis, chronic renal failure, pre-existing seizure disorder.

• Infants born of known HIV mothers.

• Clinical suspicion of necrotising enterocolitis.

• Congenital heart disease.

• Any CVS malformation:

• Congenital heart disease.

• Cyanosis before present episode.

• Presence of murmur > grade 3/6.

• Ambiguous genitalia.

• Known chromosomal abnormality.

• Infants requiring exchange transfusion.