Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01821586 |
| Other study ID # |
2006-005 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
March 27, 2013 |
| Last updated |
December 19, 2016 |
| Start date |
April 2006 |
| Est. completion date |
July 2009 |
Study information
| Verified date |
January 2006 |
| Source |
International Centre for Diarrhoeal Disease Research, Bangladesh |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Bangladesh: Ethical Review Committee |
| Study type |
Interventional
|
Clinical Trial Summary
Diarrhoea and malnutrition are the common childhood illnesses responsible for higher deaths
in developing counties. Physiologically, malnourished children excrete lower amounts of
salts and water in diarrhoeal stools, and they also are unable to handle excessive salts and
water load. Some times they are found to be hyponatraemic due to the shift of sodium inside
the cells (inefficient Na+ /K+ pump), and fluids containing higher amounts of sodium (such
as the standard ORS) may lead to further increase in the intracellular sodium, fluid
overload and heart failure. They also have depleted in potassium stores in the body.
Recently, the WHO recommended a special ORS formulation, known as ReSoMal, for management of
diarrhoea in severely malnourished children that contains a lower amount of sodium
(45mmol/L) and higher amount of potassium (40 mmol/L) than the standard WHO-ORS. It is felt
that an ORS containing lower sodium and higher potassium concentration may be useful in
correcting hypokalemia, and in lowering the risks of excess sodium and /or overhydration, in
severely malnourished children with diarrhoea. The safety of ReSoMaL is, however, still in
question due to the risk of hyponatraemia, including symptomatic hyponatraemia, especially
in the treatment of severe watery diarrhoea due to Vibrio cholerae and ETEC where loss of
sodium in the stool exceeds than that is contained in ReSoMal. Thus an ORS solution with
modest concentration of sodium (75 mmol/L) and higher concentration of potassium (40 mmol/L)
have been suggested for the treatment of diarrhoea in these children. To improve the
efficacy of oral rehydration, in terms of reducing the severity of purging and diarrhoea
duration, different approaches (changing the substrates/ reducing the sodium and glucose
concentration and osmolarity) have been tried with limited success. Benefiber (partially
hydrolysed guar gum), a soluble fiber if added to a ORS solution is expected to be fermented
in the colon liberating short chain fatty acids (SCFAs). SCFAs stimulate sodium and water
absorption from the colon, and they have trophic effect, act as a fuel source for the
colonocytes, have antibacterial properties and stimulates the production commensal flora,
thereby may enhance recovery from acute diarrhoea in severely malnourished children. The
aims of our proposed study are to examine whether an ORS solution with a modest
concentration of sodium will prevent the occurrence of hyponatraemia including symptomatic
hyponatraemia, and also whether addition of benefiber will improve the efficacy of ORS
solution. This will be a randomized, double blind, controlled clinical trial in 186 children
with severe malnutrition and watery diarrhoea (62 in each of the three treatment groups) to
compare the efficacy of (i) the currently recommended ORS with some modofication(Na+ 75
mmol/L and K40 momol/L and minerals-Zinc, copper and magnesium), (ii) ReSoMal (Na+ 45
mmol/L), (iii) Currently recommended ORS (Na+ 75 mmol/L, K 40 momol/L and added minerals)
with added Benefiber (25 grams/L), in the treatment of acute watery diarrhoea in children
with severe malnutrition
Description:
Study Design This will be a randomized, double-blind, controlled clinical trial to assess
the efficacy of three different modified ORSs: (i) Currently recommended ORS with some
modification (Na+ 75, K 40 mmol/L and added minerals); (ii) Resomal (Na+ 45); (iii)
Currently recommended ORS (Na+ 75 , K 40 mmol/L and added minerals) with added benefiber (25
grams/L) in the treatment of acute watery diarrhoea in children with severe malnutrition.
STUDY POPULATION Children of either sex, aged 6 months to 3 years, presenting with acute
watery diarrhoea of <7 days duration will be screened.
Sample Size
The sample size of this study has been determined based on the followings:
1. Persistence of hyponatraemia: We anticipate that 10% of the children will remain
hyponatraemic in the Modified ORS-1 treatment group compared to 30% children in the
Modified ORS-2 (ReSoMal). Assuming 5% level of significance and 80% power, the sample
size in each group is 60.
2. Recovery from diarrhoea: In a recent clinical trial33 of ORS solution in severely
malnourished children with acute watery diarrhoea, the mean +SD duration of diarrhoea
was 66 (32) h. We anticipate that a 25% reduction in the diarrhoea duration in children
receiving Benefiber-added ORS. Considering 5% level of significance and 80% power the
required sample size in each group is 59.
3. Anticipating a drop out of around 5% we need 62 children in each group. Randomization
After enrolment into the study the patient will be randomized to receive one of the
following three solutions:
4. Case Management:
Following the standardized protocol for management of severely malnourished children
used at ICDDR,B hospital 20,23.
5.1 Fluid therapy (oral) Dehydration will be assessed according to the WHO guidelines,
modified for in our last multicentre clinical trial of reduced osmolarity ORS in adult
cholera and children with watery diarrhoea (17). In children with some dehydration, the
fluid deficit will be corrected with the assigned ORS @ 10ml/kg/hr for the first two
hours, then 5ml /kg/hr until the deficit will be corrected. In addition, on going stool
looses will be replaced @ 5-10 ml/kg/hr after each watery stool. For high purging
patient, the ORS intake will be adjusted according to the ongoing stool loss. ORS
therapy will be continued until diarrhoea ceased. Children with severe dehydration,
initial rehydration will be done with IV fluid(cholera saline) until the patient is out
of shock or disappearance of signs of severe dehydration then the rest of the
rehydration will be done as for rehydration in patients with some dehydration as
described above.
5.2 Management of infection: Children without apparent extraintestinal infection will
receive Inj ampicillin 100 mg/kg.24 h in 3 divided doses and Inj. Gentamicin @
5ml/kg.24 h in 2 divided doses for 5 days. Children with lower respiratory tract
infection will receive Inj. Ceftriaxone 75 mg /kg.day for 5 days, and those with
cholera will receive syrup Azithromycin 20 mg/kg once within 20 minutes of
randomization.
5.3 Diet: Mothers will be advised to continue breastfeeding. Supplementary feeding with
milk suji (milk, rice powder mixture, energy 70 kcal/100ml) will be given 10 ml/Kg.feed
two hourly for day 1 and increased slowly up to 150 Kcal/Kg.day over 7 days according
to demand. If the child has poor appetite, or is weak, or has painful stomatitis or
glossitis, food will be delivered through nasogastric tube until able to take food
orally. Additionally, semisolid foods (Rice, lentil, vegetable etc.) will be given to
older children during convalescent and rehabilitation phase.
5.4 Vitamin and Mineral Supplements Children older than one year without xeropthalmia
will be given 200,000 units of vitamin A and those 6-12 months age will be given
100,000 units of vitamin A on admission. Children with xeropthalmia will receive the
same dose on three occasions: on admission, on the following day, and at discharge.
Folic acid 1.25 mg and elemental zinc 2 mg/kg will be given until discharge and some
medicine will be supplied with the patient to continue upto 15 days. Children will also
receive multivitamin drops (1 ml contains Vit A palmitate 5000 IU, vitamin D 1000 IU,
thiamine hydrochloride 1.6 mg, riboflavin 1 mg, pyridoxine hydrochloride 1 mg,
nicotinamide 10 mg, calcium D- pantothenate 5 mg, and ascorbic acid 50 mg) in a dose of
1 ml twice daily until discharge and some medicine will be supplied with the patient to
continue upto 15 days (half the dose for infants, aged <1 year). Hypoglycemia (blood
glucose <3.0 mmol/L) will be managed with 50 ml 10% glucose orally or by nasogastric
tube. Inj 25% glucose 2 ml/kg will be given if the level of blood glucose below 1.5
mmol/L. Hyponatraemia (serum sodium <115 mmol/L with or without symptoms) will be
managed with Inj. 3% NaCl 12 ml/kg I/V slowly over 4 hours.
5. Measurements 6.1 Fluids intakes ( IV, ORS and water) every 6 hours IV fluid will be
infused through a calibrated soluset, the amount infused will be noted every 6 hours if
the patient is receiving; ORS will be supplied after measuring with a calibrated
cylinder and the amount of intake will be noted every 6 hours, if any left over that
will be deducted from previous offer. Water will also be measured in a similar way.
6.2 Output (stool, urine and vomit) every 6 hours. Stool will be collected in a bucket of
known weight beneath the cholera cot with a central hole and measured every 6 hours with an
electronic scale of a precision of 1g. Urine will be collected by pediatric urine collector
bag and measured with a calibrated cylinder in ml. Vomit will be collected in a pre-weighed
bowl and measured with an electronic scale 6.3 Food intake every 6 hours The children will
be offered a defined food of known calorie after measuring with an electronic scale of
precision of 1g. Any left over will be measured and subtracted from the amount offered and
amount ingested will be recorded every 6 hours. The calorie intake will be estimated from
the amount of diet the child consumed.
6.4 Nude body weight will be measured at admission, after rehydration and every 6 hours
until recovery of diarrhoea and then at the end of every 24 hours and at discharge
