Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00244777 |
| Other study ID # |
2002-026 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
December 2002 |
| Est. completion date |
February 2004 |
Study information
| Verified date |
October 2005 |
| Source |
International Centre for Diarrhoeal Disease Research, Bangladesh |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The World Health Organization has very recently recommended the routine use of a hypo-osmolar
ORS in the management of diarrhoeal diseases. This recommendation is based on the better
efficacy of the hypo-osmolar ORS over the standard WHO ORS demonstrated in controlled
clinical trials. The recommendation, however, also expressed the need for "careful monitoring
to better assess risk, if any, of symptomatic hyponatraemia". There thus is a need for phase
IV trials before the new solution is introduced into routine clinical practice to assess the
risk in relatively large number of patient populations. The proposed study will be carried
out at two different settings- at the urban settings of the Dhaka Hospital (60000 patients)
and at the rural settings of the Matlab Hospital (15000 patients) of ICDDR,B. The
hypo-osmolar rice or glucose-based ORS will be introduced as standard management of patients
with diarrhoea . The hypo-osmolar ORS will contain 75 mmol /L of sodium instead of 90 mmol/L.
Surveillance will be carried out to detect adverse events focusing on the occurrence of
seizures or undue lethargy during hospitalization. Each episode of seizure or undue lethargy
would be evaluated to determine if they are associated with abnormal levels of serum sodium
or glucose, or fever. It has been estimated that about 3% (1,800) of patients initially
admitted to the Short Stay Ward of the Dhaka Hospital, and 340 patients at the Matlab
Hospital might require admission to the longer stay inpatient wards due to seizure or altered
consciousness. Such patients would be thoroughly assessed including determination of their
serum sodium and glucose, two common causes of seizures/altered consciousness, to determine
if and to what extent they could be attributed to hyponatraemia.The results from this study
would be used in planning and implementing the routine use of the new formulation of ORS at
all Government, NGO and private health care facilities that treat diarrhoeal patients, in
Bangladesh and in other countries.
Description:
Study site: The Dhaka and the Matlab Hospitals of ICDDR, B: Centre for Health and Population
Research.
Duration: Total duration of 15 months that include data collection over a full year to
capture seasonal variations in the aetiology of diarrhoea.
Sample size: Based on the yearly patient visits it is estimated that 60,000 patients would be
studied at the Dhaka Hospital and 15,000 patients at the Matlab Hospital.
Inclusion criteria
All patients attending the Dhaka and Matlab hospitals who will be admitted to the Short Stay
Ward with uncomplicated watery diarrhoea would be eligible for this study.
Exclusion criteria
Patients with complications, and those with severe illness that require special care or
multiple interventions would be excluded.
Procedures
Infants 6 month of age or younger would receive the glucose-based (75 mmol/L) ORS ( Na: 75,
Cl: 65, K: 20, citrate:10, glucose: 75, and osmolarity: 245 mOsm/L), and those older than 6
months would receive the rice-based ORS (40 g/L of rice powder); both will contain 75 mmol/L
of sodium, 65 mmol/L of chloride, 20 mmol/L of potassium, and 10 mmol/L of citrate with an in
vitro osmolarity of 170 mOsm/L. This is in line with the Centre's policy of not adding starch
for management of infants 6 months of age or younger.
Surveillance and case management
Dhaka Hospital: From our experience about 3% patients (1,800 patients/year) initially
admitted to the Short Stay Ward are subsequently admitted to the Longer Stay Wards due to
development of symptoms like seizure, lethargy or altered consciousness. Patients admitted to
the Short Stay Ward who receive ORS solution for 8 hours or more, and subsequently admitted
to inpatient ward for the above symptoms will be evaluated to determine if they are due to
hyponatraemia. Similarly, 3% of the patients attending the Matlab Hospital (340
patients/year) might develop these symptoms and will be evaluated if their symptoms are due
to hyponatraemia.
All clinical and laboratory data of these patients will be maintained during the study.
Assessment and management of patients Hospitals current protocol for assessment of the cause
of lethargy and seizures such as estimation of plasma glucose, serum electrolytes, fever, and
study of the cerebrospinal fluids where clinically indicated would be employed for diagnosing
the aetiology of the symptoms.
Protocol for management of seizure
Although rare, the development of seizures during the rehydration therapy for acute watery
diarrhoea would be considered as a serious adverse event. Patients developing such symptoms
would be assed to determine if they could be attributed to hyponatraemia. The same protocol
for management of seizure would be used at both of the study sites, which would be as
follows:
Procedures:
- All patients developing significant lethargy and seizure while on ORS would be
immediately admitted to the special care unit.
- An intravenous line will be opened for medication.
- Blood glucose will be measured immediately from finger blood sample using bedside
glucose monitoring machine, and blood sample would be obtained for estimation of serum
electrolytes, calcium, and magnesium at the clinical laboratories of the Centre.
- Hypoglycaemic (<2.2 mmol/L) patients would be immediately given intravenous glucose (25%
glucose; 2 ml/kg), which would be followed by oral (or through nasogastric tube of
patients who are unable to drink) administration of 10% glucose in a dose of xxxxx
- Diazepam (0.3 mg/Kg) would be administered to patients who are not hypoglycaemia, and
also to patients who are hypoglycaemic but do not respond to initial glucose infusion.
- If seizure persists, the same dose of intravenous diazepam would be repeated for the
second time, and injectable phenobarbitone would also be administered (15-20 mg/kg
loading dose, followed by 2.5 mg/Kg every 12 hours as the maintenance dose).
- After control of seizure, a lumber tap will be done to rule out meningitis if clinically
indicated (i.e. patients suspected to have meningitis).
- A sample of blood will also be sent for culture to exclude septicaemia
- X-Ray chest will be done to exclude pneumonia if clinically indicated (following WHO
guidelines)
- Patients with a serum sodium of ≤120 mmol/L will be treated with 3% NaCl in a dose of 1
ml/Kg.hour for the next 4 hours (i.e. total of 12 ml/Kg over the 4-hour period), along
with restriction of plain water.
- Hypernatraemic patients (serum sodium >150 mmol/L) would be treated with the same ORS
but with provision for water ad lib.
- Patients suspected for extra intestinal infection including sepsis will be treated with
Inj. Ampicillin and Inj. Gentamicin (infants aged 3 months or younger) or Inj.
Ceftriaxone and Gentamicin (patients aged more than 3 months) for 7 days.
