Zinc-ORS in Severe and Complicated Acute Diarrhea
Zinc-ORS in Severe and Complicated Acute Diarrhea
Three-hundred-and-fifty-two males aged 1-36 months with acute non-dysenteric diarrhoea and no
 systemic illness will be enrolled in this clinical trial. Eligible children will be
 stratified by their age (1up to 5 months, 6-35 months). Within the two age strata the
 patients will be randomized to receive zinc-ORS (fortified with 40 mg elemental zinc as zinc
 gluconate per litre) or standard WHO ORS. The major outcome measures will be stool output and
 duration of diarrhea. The safety of administering zinc will be determined by examining the
 effect of zinc ingestion on vomiting, sodium and potassium homeostasis, plasma zinc and
 copper, and iron stores and concentration of serum transferrin receptor.
Zinc deficiency is prevalent in developing countries due to inadequate food intake, low
 intake of foods from animal sources and high dietary intake of phytate, a substance that
 reduces zinc absorption. A recently completed trial at All India Institute Of Medical
 Sciences (AIIMS) measured the effect of zinc-ORS in the community, where most episodes are
 relatively mild. Zinc-ORS was efficacious in reducing the total number of stools (19%
 relative risk reduction, 95% CI 15% to 23%) and duration of diarrhoea (11% relative risk
 reduction, 95% CI 4% to 24%). In order to make policy decisions that standard ORS provided to
 children be fortified with zinc the national (and international) child health programs need a
 similar evidence base also for children hospitalized because of acute diarrhea. This is
 because these children represent the more severe end of the disease spectrum, i.e. they are
 the ones who are at the highest risk of dying.

 The primary objective is to conduct a study of zinc-ORS in a hospital setting (i.e. of more
 severe diarrhea) to optimize and accurately measure the amount of zinc-ORS consumed and
 monitor stool output which is not possible in a field setting. The study will also examine
 the safety of using zinc-ORS; whether zinc-ORS affects the blood levels of sodium and
 potassium and of other micronutrients than zinc, such as copper and iron. The study will
 contribute to introducing a more efficacious ORS and help increase the ORS use rate which
 continues to be an important public health challenge in India.

 The study will be carried out at two Clinical Research Facilities supervised by the Centre
 for Diarrhoeal Diseases and Nutrition Research, Division of Gastroenterology, Department of
 Pediatrics, AIIMS. 352 males aged 1-36 months with acute non-dysenteric diarrhoea and no
 systemic illness will be enrolled. Eligible children will be first stratified by their age
 (1up to 5 months, 6-35 months). Within the two age strata the patients will be randomized to
 receive zinc-ORS (fortified with 40 mg elemental zinc as zinc gluconate per litre) or
 standard WHO ORS. The major outcome measures will be stool output and duration of diarrhea.
 The safety of administering zinc will be determined by examining the effect of zinc ingestion
 on vomiting, sodium and potassium homeostasis, plasma zinc and copper, and iron stores and
 concentration of serum transferrin receptor. Minimum period of the study will be 48 hours and
 subjects will be discharged when diarrhoea has ceased or at 48 hours, whichever is later.
Inclusion Criteria:

 -  Males

 -  Age 1 month up to 36 months:

 -  Passage of 3 or more liquid stools in a 24-hour period, every day, and at least one in
 12 hours prior to admission

 -  Diarrhea for < 7days (168 hours)

 Exclusion Criteria:

 -  severe systemic illness requiring intensive care management; systemic infection will
 be suspected if there is a general appearance of non-wellbeing with one or more of the
 following symptoms: shrill cry and irritability, temperature instability, hypotension,
 hypoglycemia, altered sensorium, lethargy or refusal of feeds, abdominal distension.

 -  chronic illness like Tuberculosis, Nephrotic syndrome, malignancy etc or any surgical
 disorder.

 -  severe malnutrition (weight for age <65% of NCHS median

 -  gross blood in stool

 -  refusal of consent