Plain English Summary

Background and study aims
Diarrhoea causes an estimated 2.5 million child deaths in developing countries each year, 35% of which are due to acute diarrhoea. Zinc and copper stores in the body are known to be depleted during acute diarrhoea. Our objectives were to evaluate the efficacy of zinc and copper supplementation when given with standard treatment to children with acute watery or bloody diarrhoea.

Who can participate?
Inclusion Criteria
1. Children with Six to 60 months of age, either sex
2. Presence of diarrhoea
3. Duration of diarrhoea ≤ 72 hours prior to admission
4. Ability to take oral feeds or breast feeds
5. Caretaker willing to sign informed consent
Exclusion criteria
1. Serious complicating illness/disease
2. Clinically apparent kwashiorkor (malnutrition)
3. Residence more than 30 km from Nagpur
4. Previously enrolled in this trial

What does the study involve?
The treatment groups were:
1. Zinc alone
2. Zinc and copper
3. Placebo with each of these treatment groups divided in two sub-groups based on frequency of dose
Each treatment was administered either once a day or 6 hourly during hospitalisation and the allocation ratio across all the six groups was uniform. After discharge, the supplements were only administered as a single daily dose to all children. These doses of supplements were administered for a total duration of two weeks from enrolment in the trial including after discharge from hospital.

What are the possible benefits and risks of participating?
There are no known side effects from taking zinc and copper supplements in the amounts that will be given to your child during this study. It is possible that these supplements will hasten your child’s recovery from diarrhoea and prevent further illnesses following discharge from hospital. Two additional blood collections will be required and these may cause some pain and distress to your child. To minimize this discomfort we will use a cream on the skin to reduce any pain.

Where is the study run from?
Indira Gandhi Government Medical College, Nagpur, India

When is the study starting and how long is it expected to run for?
The study started in September 2003 and ended in October 2006.

Who is funding the study?
The Welcome Trust (UK)

Who is the main contact?
Dr. Archana B. Patel
dr_apatel@yahoo.com
ceuiggmc@yahoo.co.in

Trial website

Contact information

Type

Scientific

Primary contact

Dr Archana Patel

ORCID ID

Contact details

125
Katol Road
Opp. Tidke Vidyalaya
Nagpur - 18
Nagpur
440013
India
dr_apatel@yahoo.com

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

GR068664AIA

Study information

Scientific title

Zinc and copper supplementation in treatment of acute diarrhoea in children: a randomised controlled clinical trial

Acronym

CDP

Study hypothesis

In a randomised controlled trial of supplementation for 2 weeks of 2 mg/kg/day of zinc or 2 mg/kg/day of zinc and 0.2 mg/kg/day of copper together with standard treatment, given to children hospitalised for acute diarrhoea, the children supplemented with zinc alone in comparison to the placebo group, or the children supplemented with zinc and copper in comparison to placebo group will at least experience the following.

Primary hypotheses:
1. 15% reduction in the mean duration of diarrhoea following admission to hospital
2. 50% reduction in the proportion of children with acute diarrhoea lasting more than seven days from onset
3. 25% reduction in the total stool output weight

Secondary hypotheses:
4. 30% increase in the proportion of children who are successfully rehydrated with oral rehydration solution
5. Increasing the frequency of dosage will increase the beneficial impact of zinc and copper supplementation on the clinical outcomes of acute diarrhoeal disease
6. 20% reduction in predicted mean total cost of treating patients with acute diarrhoea in the zinc and copper supplemented study groups as compared to the placebo group from the patient and provider’s perspective

Tertiary hypotheses:
7. 50% reduction in the proportion of children with acute diarrhoea who experience any the following complications:
7.1. Haemolytic uraemia syndrome
7.2. Septicaemia
7.3. Death
8. The effect of zinc and copper supplementation on each specific clinical indicator is different depending on the initial zinc status, initial anthropometric status, age and breastfeeding status

Ethics approval

Ethics approval received from:
1. Indira Gandhi Government Medical College (IGGMC) on the 18th January 2003 (ref: 19/8/10/02)
2. University of Newcastle Ethics Committee (ref: H-500-0203)

Study design

Randomised, double blind, placebo controlled clinical trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Acute diarrhoea

Intervention

The treatment groups were:
1. Zinc alone
2. Zinc and copper
3. Placebo with each of these treatment groups divided in two sub-groups based on frequency of dose

Each treatment was administered either once a day or 6 hourly during hospitalisation and the allocation ratio across all the six groups was uniform. After discharge, the supplements were only administered as a single daily dose to all children. The dose of zinc was 2 mg/kg body weight/day and that of copper was 0.2 mg/kg body weight/day. These doses of supplements were administered for a total duration of two weeks from enrolment in the trial including after discharge from hospital.

Intervention type

Supplement

Phase

Not Applicable

Drug names

Zinc supplementation, copper supplementation

Primary outcome measures

In-hospital:
1. Mean duration of diarrhoea of 3.9 days, measured every day for two weeks
2. Duration of diarrhoea (mean duration greater than 7 days from onset of episode), measured every day for two weeks
3. Time/rate of rehydration, measured every day for two weeks
4. Total stool output (weight), measured every day for two weeks
5. Amount of Oral Rehydration Solution (ORS) used, measured every day for two weeks
6. Amount of Intravenous (IV) fluids used, measured every day for two weeks
7. Weight change: on admission, after 4 hours and then every 24 hours

Secondary outcome measures

In-hospital:
1. Cost of supplements versus standard treatment
2. Rates of complications (measured every day for two weeks):
2.1. Electrolyte imbalance
2.2. Haemolytic uraemic syndrome
2.3. Septicemia
2.4. Death
3. Differential effects depending on clinical indicators:
3.1. Initial zinc status, measured once at baseline and on 14th day
3.2. Age, measured every fortnight over a 3 month period following discharge
3.3. Breastfeeding status, measured every fortnight over a 3 month period following discharge
3.4. Anthropometric indicators, measured every fortnight over a 3 month period following discharge

Overall trial start date

01/09/2003

Overall trial end date

30/10/2006

Reason abandoned

Eligibility

Participant inclusion criteria

1. Six to 60 months of age, either sex
2. Presence of diarrhoea
3. Duration of diarrhoea less then or equal to 72 hours prior to admission
4. Ability to take oral feeds or breast feeds
5. Caretaker willing to sign informed consent

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

808

Participant exclusion criteria

1. Serious complicating illness/disease
2. Clinically apparent kwashiorkor
3. Residence more than 30 km from Nagpur
4. Previously enrolled in this trial

Recruitment start date

01/09/2003

Recruitment end date

30/10/2006

Locations

Countries of recruitment

India

Trial participating centre

125, Katol Road
Nagpur
440013
India

Sponsor information

Organisation

University of Newcastle (Australia)

Sponsor details

c/o Dr Michael J. Dibley
Senior Lecturer in Epidemiology
Centre for Clinical Epidemiology & Biostatistics
Faculty of Health
Upper Level - Bowman Building
University Drive
Callaghan
NSW 2308
Australia

Sponsor type

University/education

Website

http://www.newcastle.edu.au/

Funders

Funder type

Charity

Funder name

The Wellcome Trust (UK) (grant ref: 068664)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23177894

Publication citations

  1. Results

    Patel AB, Badhoniya N, Dibley MJ, Zinc and copper supplementation are not cost-effective interventions in the treatment of acute diarrhea., J Clin Epidemiol, 2013, 66, 1, 52-61, doi: 10.1016/j.jclinepi.2012.06.012.

Editorial Notes