Ignite Creation Date:
2024-05-05 @ 12:03 PM
Last Modification Date:
2024-10-26 @ 9:19 AM
Study NCT ID:
NCT00226616
Status:
COMPLETED
Last Update Posted:
2005-10-20
First Post:
2005-09-25
Brief Title:
Zinc Supplementation in Cholera Patients
Sponsor:
International Centre for Diarrhoeal Disease Research Bangladesh
Organization:
International Centre for Diarrhoeal Disease Research Bangladesh
Study Overview
Official Title:
Clinical Trial of Zinc Supplementation in Cholera Patients
Status:
COMPLETED
Status Verified Date:
2005-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Cholera is one of the leading causes of morbidity and mortality among children and adult in developing countries We will evaluate the effect of supplementation of zinc on reduction of duration and severity of cholera Since cholera is primarily a disease of older children and adults we intend to study the effects of zinc supplementation among children of 3 to 14 years of age whose initial stool weight will be 4mlkghour in 1st 6 hours and dark field examination is positive 90 subjects in each group hospitalized with cholera with diarrhea for less than 24 hours will be selected After inclusion in the study informed consent will be obtained from guardian explaining the full procedure in the hospital The subjects will be randomized to receive either zinc or placebo until diarrhea resolves History of illness and baseline information will be collected in the hospital through interview which may take duration of 10 minutesAfter 6 hours of initial rehydration fluid balance study will be carried out on all subjects until diarrhea resolves 1 ml 14 teaspoonful of blood sample will be taken to assess serum zinc level on admission after initial hydration and will be repeated on the day of recovery This procedure carries a small risk of infection if not done under sanitary conditions however we will maintain proper sanitation so there is no risk in the procedures There is no potential risk in this study20mg elemental Zinc will be given daily in 2 divided doses till cholera resolves Both groups will receive syrup or tablet Erythromycin 50mgkg24 in 4 divided doses for 3 days Oral rehydration solutionintravenous acetate fluid will be used for rehydration Daily body weight will be taken and stool will be sent for CS until the day of recovery or 5 days Zinc loss in stool will be seen in 20 of random stool samples Information obtained from history and the laboratory investigations of subject will be kept strictly confidential and no one other than the investigators of this study and the Ethics Committee of this Centre will has access to the information The study will benefit the patients as study physician will do close observation examination and will take care frequently as research staff will monitor systematic progress and take necessary action Study micronutrient zinc is shown to have benefit in children in acute diarrhea If the results of the study is positive it will benefit the patients in their treatment during this study and thereafter The data will be analyzed for clinical effects of zinc on diarrheaThe study will help to improve the treatment strategy of cholera in children The study will use hospital records which will be returned after completion of the study Stool urine and 1 ml 14 teaspoonful of venous blood will be taken to assess serum zinc level
Detailed Description:
Study design
A double blind randomized clinical trial using zinc and placebo
Randomization
Patients will be randomized to one of two groups A or B Block randomization will be done using block length of 6 Group A will receive Zinc Erythromycin and Group B will receive PlaceboErythromycin
Dose of Erythromycin
Syruptab Erythromycin 50mgkg24 hours in 4 divided doses for 3 days
Dose of zinc
Zinc acetate will be given at 10mg twice daily 10mgx220mg elemental zinc until cholera resolves the time of passage of last unformed stool or first formed stool followed by 24 hours without any diarrheal stool
Composition of the syrup
For both groups the bulk of the base syrup will be consist of the same chemicals in addition to this group A will have the treatment substance ie elemental zinc 20 mgday
Syrup A Quantity per 5 ml
Zinc Acetate 10 mg elemental zinc
Syrup B Base substance
Base Substance
Ascorbic acid 30 mg Glycerin USP 12 ml Propylene glycol USP 075 ml Sorbitol 70 BP 20 ml Methyl Paraben USFN 35 mg Polysorate-80 50 mg Tween -80 BPC Lemon oil PH grade 00125 ml Caramel Brown colour 1 mg Purified water 075 ml
Clinical procedure in the hospital
Patients who meet the selection criteria will be observed for initial six hours while their urine and stool specimen will be collected separately Patient whose initial stool-output 4mlkghour during this period and dark field examination of stool is positive will be enrolled in the study Patients will be kept in study ward After complete hydration patients will be randomised in blocks of 6 to one of two groups A and B Group A will receive syrup zinc and group B will receive placebo till cholera resolves Both the groups will receive the identical bottles containing syrup with same flavor and only single unique serial number will be written on the bottles The number will indicate an exact subject of study Both the groups will receive SyrupTab Erythromycin 1ml blood will be collected for serum zinc on admission after complete dehydration and this test will be repeated at the time of discharge Stool culture and sensitivity CS will be sent daily until the day of recovery or 5 days Balance will be performed on all the patients till cholera resolves If any complication develops after enrollment study will be discontinued and patient will be treated accordingly
Assessment of dehydration
To reduce observational variation especially regarding the assessment of dehydration a standardized form is developed for the assessment of dehydration
CONDITION 1normal 2irritablelessactive 3lethargiccomatose MUCOSA 1normal 2dry
EYES 1normal 2sunken THIRST 1normal 2thirsty 3unable to drink SKIN TURGOR 1normal 2reduced PULSE 1normal 3feebleabsent
DEHYDRATION STATUS
1 no sign of dehydration
2 some dehydration two signs coded 2 with at least one key sign
3 severe dehydration some dehydration plus one key sign coded 3
This method was recently validated by a group of international experts in oral rehydration therapy who were invited to ICDDR B and is currently being used in a large WHO sponsored multi-centre trial for the evaluation of low osmolarity ORS The investigators have been trained in this method
Rehydration phase
All the patients recruited in this study will have either some dehydration or severe dehydration Therefore before being randomized into study during initial 6 hours all the patients will be rehydrated either by ORS or intravenous fluid Patients with signs of some dehydration will be rehydrated by ORS and patients with severe dehydration will be rehydrated intravenously as described below The following IV fluids will be used
Sodium Potassium Chloride Acetate Dhaka Solution mmolL mmolL mmolL mmolL 133 13 98 48 Rate of administration will be 100 mlkg over 4 hours plus volume-for-volume replacement for ongoing losses hourly
If at the end of four hours
1 The patient is fully rehydrated heshe will be randomized to one of the treatment groups
2 Some dehydration persist IV infusion will continue at the rate of 50 ml kg over 2 hours plus replacement volume for volume of ongoing losses
3 Severe dehydration persists IV infusion will continue for an additional 2 hours at the rate of 100 mlkg plus replacement of ongoing losses This is very unusual however occurring only in very few patients who pass large watery stools frequently
If at the end of six hours the patient is fully rehydrated patient will be randomized to one of the treatment group If signs of dehydration persist after 6 hours the patient will be excluded from study All intake and output during this initial rehydration phase will be recorded
Maintenance phase
After completion of rehydration subjects will be randomized to one of the two groups Group A and Group B Group A will be given zinc acetate and group B will be given placebo The supplementation of zinc or placebo will be continued till diarrhea resolves Ongoing stool losses will be replaced with equal volume of Rice-ORS
Dietary management
Standardize hospital diet will be given to all patients which includes milk suji rice vegetable daal bread banana and chicken or fish
Intake and output measurement
All oral and intravenous fluid will be measured and recorded until cholera resolves Stool weight will be measured separately from urine every 8 hours until cholera resolves Urine will be separated and measured 8 hourly weight of vomitus will also be taken 8 hourly Daily clinical examination will be done by the investigators and study physician with observation on stool consistency and character
Clinical recovery
Clinical recovery will be defined as the time of passage of last unformed stool or first formed stool followed by 24 hours without any diarrheal stool
Sample size calculation
We assume that zinc will reduce 20 of mean duration of illness compared to erythromycin group18 at 90 power and 5 level of confidence Therefore the sample size will be
n2 SD2 aßD2 n2 52 105262 n776678 per treatment group So the total number of samples will be 78 x 2 156 Considering 15 drop out the total number of samples will be 15624180
Assessment of weight gain
Weight will be taken on admission and daily until cholera resolves
Laboratory tests
1 Microscopic examination
1 Dark field examination will be done on stool samples on admission
2 Microbiological assays
1 Daily stool CS will be done till cholera resolves or 5 days
3 Micronutrient assay
1 Serum zinc level will be obtained on day 1 and on the day of recovery
2 Randomly zinc loss in cholera will be seen in 20 samples
A double blind randomized clinical trial using zinc and placebo
Randomization
Patients will be randomized to one of two groups A or B Block randomization will be done using block length of 6 Group A will receive Zinc Erythromycin and Group B will receive PlaceboErythromycin
Dose of Erythromycin
Syruptab Erythromycin 50mgkg24 hours in 4 divided doses for 3 days
Dose of zinc
Zinc acetate will be given at 10mg twice daily 10mgx220mg elemental zinc until cholera resolves the time of passage of last unformed stool or first formed stool followed by 24 hours without any diarrheal stool
Composition of the syrup
For both groups the bulk of the base syrup will be consist of the same chemicals in addition to this group A will have the treatment substance ie elemental zinc 20 mgday
Syrup A Quantity per 5 ml
Zinc Acetate 10 mg elemental zinc
Syrup B Base substance
Base Substance
Ascorbic acid 30 mg Glycerin USP 12 ml Propylene glycol USP 075 ml Sorbitol 70 BP 20 ml Methyl Paraben USFN 35 mg Polysorate-80 50 mg Tween -80 BPC Lemon oil PH grade 00125 ml Caramel Brown colour 1 mg Purified water 075 ml
Clinical procedure in the hospital
Patients who meet the selection criteria will be observed for initial six hours while their urine and stool specimen will be collected separately Patient whose initial stool-output 4mlkghour during this period and dark field examination of stool is positive will be enrolled in the study Patients will be kept in study ward After complete hydration patients will be randomised in blocks of 6 to one of two groups A and B Group A will receive syrup zinc and group B will receive placebo till cholera resolves Both the groups will receive the identical bottles containing syrup with same flavor and only single unique serial number will be written on the bottles The number will indicate an exact subject of study Both the groups will receive SyrupTab Erythromycin 1ml blood will be collected for serum zinc on admission after complete dehydration and this test will be repeated at the time of discharge Stool culture and sensitivity CS will be sent daily until the day of recovery or 5 days Balance will be performed on all the patients till cholera resolves If any complication develops after enrollment study will be discontinued and patient will be treated accordingly
Assessment of dehydration
To reduce observational variation especially regarding the assessment of dehydration a standardized form is developed for the assessment of dehydration
CONDITION 1normal 2irritablelessactive 3lethargiccomatose MUCOSA 1normal 2dry
EYES 1normal 2sunken THIRST 1normal 2thirsty 3unable to drink SKIN TURGOR 1normal 2reduced PULSE 1normal 3feebleabsent
DEHYDRATION STATUS
1 no sign of dehydration
2 some dehydration two signs coded 2 with at least one key sign
3 severe dehydration some dehydration plus one key sign coded 3
This method was recently validated by a group of international experts in oral rehydration therapy who were invited to ICDDR B and is currently being used in a large WHO sponsored multi-centre trial for the evaluation of low osmolarity ORS The investigators have been trained in this method
Rehydration phase
All the patients recruited in this study will have either some dehydration or severe dehydration Therefore before being randomized into study during initial 6 hours all the patients will be rehydrated either by ORS or intravenous fluid Patients with signs of some dehydration will be rehydrated by ORS and patients with severe dehydration will be rehydrated intravenously as described below The following IV fluids will be used
Sodium Potassium Chloride Acetate Dhaka Solution mmolL mmolL mmolL mmolL 133 13 98 48 Rate of administration will be 100 mlkg over 4 hours plus volume-for-volume replacement for ongoing losses hourly
If at the end of four hours
1 The patient is fully rehydrated heshe will be randomized to one of the treatment groups
2 Some dehydration persist IV infusion will continue at the rate of 50 ml kg over 2 hours plus replacement volume for volume of ongoing losses
3 Severe dehydration persists IV infusion will continue for an additional 2 hours at the rate of 100 mlkg plus replacement of ongoing losses This is very unusual however occurring only in very few patients who pass large watery stools frequently
If at the end of six hours the patient is fully rehydrated patient will be randomized to one of the treatment group If signs of dehydration persist after 6 hours the patient will be excluded from study All intake and output during this initial rehydration phase will be recorded
Maintenance phase
After completion of rehydration subjects will be randomized to one of the two groups Group A and Group B Group A will be given zinc acetate and group B will be given placebo The supplementation of zinc or placebo will be continued till diarrhea resolves Ongoing stool losses will be replaced with equal volume of Rice-ORS
Dietary management
Standardize hospital diet will be given to all patients which includes milk suji rice vegetable daal bread banana and chicken or fish
Intake and output measurement
All oral and intravenous fluid will be measured and recorded until cholera resolves Stool weight will be measured separately from urine every 8 hours until cholera resolves Urine will be separated and measured 8 hourly weight of vomitus will also be taken 8 hourly Daily clinical examination will be done by the investigators and study physician with observation on stool consistency and character
Clinical recovery
Clinical recovery will be defined as the time of passage of last unformed stool or first formed stool followed by 24 hours without any diarrheal stool
Sample size calculation
We assume that zinc will reduce 20 of mean duration of illness compared to erythromycin group18 at 90 power and 5 level of confidence Therefore the sample size will be
n2 SD2 aßD2 n2 52 105262 n776678 per treatment group So the total number of samples will be 78 x 2 156 Considering 15 drop out the total number of samples will be 15624180
Assessment of weight gain
Weight will be taken on admission and daily until cholera resolves
Laboratory tests
1 Microscopic examination
1 Dark field examination will be done on stool samples on admission
2 Microbiological assays
1 Daily stool CS will be done till cholera resolves or 5 days
3 Micronutrient assay
1 Serum zinc level will be obtained on day 1 and on the day of recovery
2 Randomly zinc loss in cholera will be seen in 20 samples
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None