Zinc-ORS in Severe and Complicated Acute Diarrhea

Phase 2

Completed

• Conditions: Diarrhea; Dehydration

• Registration Number: NCT00370968
• Lead Sponsor: Centre For International Health

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2003-09
• Study First Submitted: 2006-08-31
• Study First Submitted QC: 2006-08-31
• Study First Posted: 2006-09-01
• Study Completion: 2006-12
• Status Verified: 2010-05
• Last Update Submitted: 2010-05-12
• Last Update Posted: 2010-05-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 352

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Stool output (g/kg/24h)
Duration of diarrhoea (days).

Trial Locations

Locations (2)

All India Institute of Medical Sciences; 🇮🇳 New Delhi, India

Deen Dayal Upadhyaya Hospital; 🇮🇳 New Delhi, India