Clinical trial NCT00530374: Impact of Sprinkles on Infectious Morbidity When Moderate to Severe Pediatric Malnutrition Is Highly Prevalent
Official title: Impact of Oral Iron Supplementation With Sprinkles on Infectious Morbidity When Moderate to Severe Pediatric Malnutrition Is Highly Prevalent - A Non-Inferiority Safety Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malnutrition
Iron Deficiency
Keywords: Pediatrics
Malnutrition
Iron Deficiency
Sprinkles
Oral Iron Supplementation
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: Bangladesh Rural Advancement Committee
name: International Centre for Diarrhoeal Disease Research, Bangladesh
First posted: 2007-09-17
Enrollment: 268
Sex: ALL
Minimum age (years): 1
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety profile of oral iron supplementation (OIS) with Sprinkles in a pediatric population with high prevalence of Iron deficiency (ID) and moderate or severe malnutrition (MSM); the efficacy profile will also be investigated.

Detailed description: Iron deficiency (ID) affects many children in developing countries. Anemia and impaired brain development are its most significant consequences. These may be prevented by giving oral iron supplements (OIS), such as Sprinkles. ID treatment was controversial because high dose parenteral iron therapy is strongly associated with severe infections when given to severely malnourished children. Many studies have since demonstrated the safety of low dose OIS. WHO guidelines reflect this finding: population-wide iron supplementation campaign (PWISC), without prior screening, is recommended when ID prevalence is ≥ 40%.

However, a gap in the safety evidence has been identified: children with moderate or severe malnutrition (MSM) are strikingly absent from the studies performed to date to investigate the link between OIS and infectious morbidities. In this context, PWISC may have unrecognized deleterious effects when the prevalence of MSM is high, since safety is assumed, but incorrectly extrapolated from available evidence.

We wish to emphasize an additional concern with regards to safety studies published thus far: all were designed as superiority trials. In this context, it is statistically incorrect to conclude that failure to show a significant difference between iron and placebo means that their respective side-effect profiles are similar.

Eligibility criteria: Inclusion Criteria:

* children aged 12 - 24 months
* moderate to severe malnutrition (MSM), defined as weight-for-age Z-score ≤ -2 based on the National Center for Health Statistics (NCHS) standards

Exclusion Criteria:

* severe anemia (hemoglobin ≤70g/L)
* near normal hemoglobin concentration (\>100g/L)
* weight-for-height \<-3 z-score (severe wasting)
* kwashiorkor (defined as evidence of edema)
* congenital abnormality or disease
* treatment with iron supplements in the past 3 months
* inclusion in a nutrition program in the past
* chronic illness other than malnutrition.

Primary outcomes:
measure: A composite score based on the sum of all distinct episodes of diarrhea, dysentery and lower respiratory tract infections
timeFrame: 2 distinct and consecutive phases of 6 months each
Secondary outcomes:
measure: Incidence of death and fever without a source [Safety]
timeFrame: 2 distinct and consecutive phases of 6 months each
measure: Change in haemoglobin concentration after Sprinkles supplementation [Efficacy]
timeFrame: 2 distinct and consecutive phases of 6 months each
Other outcomes:
Locations:
city: Shombhuganj
country: Bangladesh
facility: Village of Shombhuganj
state: Mymensingh District
Study officials:
affiliation: The Hospital for Sick Children, Toronto Canada
name: Stanley Zlotkin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lemaire M, Islam QS, Shen H, Khan MA, Parveen M, Abedin F, Haseen F, Hyder Z, Cook RJ, Zlotkin SH. Iron-containing micronutrient powder provided to children with moderate-to-severe malnutrition increases hemoglobin concentrations but not the risk of infectious morbidity: a randomized, double-blind, placebo-controlled, noninferiority safety trial. Am J Clin Nutr. 2011 Aug;94(2):585-93. doi: 10.3945/ajcn.110.009316. Epub 2011 Jun 29.