Ignite Creation Date:
2024-05-05 @ 4:52 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00333944
Status:
COMPLETED
Last Update Posted:
2006-06-06
First Post:
2006-06-05
Brief Title:
Study to Know the Efficacy of Higher Doses of Pralidoxime in Patients of Organophpsphorus Poisoning
Sponsor:
Giriraj Hospital
Organization:
Giriraj Hospital
Study Overview
Official Title:
Effectiveness of High Dose Pralidoxime in the Treatment of Organophosphorus Pesticide Poisoning - a Randomised Controlled Trial
Status:
COMPLETED
Status Verified Date:
2000-05
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:
The purpose of this study is to determine whether high doses of pralidoximePAM are effective as compare to lower doses of PAM in the management of moderately sever organophosphorus poisoning patients
Detailed Description:
Standard treatment of organophosphorus pesticide poisoning involves administration of intravenous atropine and oximes to counter acetylcholinesterase inhibition1 Treatment with atropine is well established but the efficacy and dosage schedule of oximes are controversial2-5 A dose of 1g every four to six hours has been the standard regimen in Asian district hospitals but many clinicians remain unconvinced by its effectiveness3 Randomised controlled trials RCT performed in Vellore during the nineties compared a 12g infusion over 3-4 days with a 1g bolus dose and then with placebo67 The authors reported no benefit from pralidoxime and an increased mortality in those receiving the infusion and have stated that pralidoxime should not be given to organophosphorus poisoned patients2
Others consider that the dosage regimen was not ideal with therapeutic concentrations being obtained rarely during the treatment34 Furthermore many patients presented late and had taken dimethyl pesticides - a class that does not respond well to oximes after several hours - biasing the study against finding benefit
The proposed minimum effective plasma levels for pralidoxime of 4 mgL were based on in vitro and animal experiments by Sundwall8 Recent evidence however suggests that higher blood concentrations of pralidoxime are needed to antagonise the toxic effects of many pesticides and that a bolus loading infusion followed by a maintenance infusion would be the best regimen9 The WHO have proposed that patients receive around 30mgkg pralidoxime salt as a loading dose followed by an infusion of at least 8mgkghr roughly equivalent to 1-2 g bolus followed by 05 gh in a 50kg south Asian patient910 However no trials have yet been performed to determine whether such a regimen reduces morbidity and mortality in severely poisoned patients3 Since organophosphorus pesticides kill hundreds of thousands of people in rural Asia every year it is essential to determine whether it benefits or harms such poisoned patients
Our hospital has typically used a regimen of 1g q4h in organophosphorus poisoned patients but we were unconvinced about the effectiveness of this expensive drug since many patients required ventilation for 10 days We informally treated several patients with the WHO-recommended regimen but saw little benefit Since pralidoxime has a high therapeutic index we then decided to conduct a RCT with still higher doses ie to compare a 1 g infusion every hour q1h 24 gday with 1g every four hours q4h 6 gday after a 2 g loading dose to assess the effectiveness of high dose pralidoxime in organophosphorus poisoned patients
Others consider that the dosage regimen was not ideal with therapeutic concentrations being obtained rarely during the treatment34 Furthermore many patients presented late and had taken dimethyl pesticides - a class that does not respond well to oximes after several hours - biasing the study against finding benefit
The proposed minimum effective plasma levels for pralidoxime of 4 mgL were based on in vitro and animal experiments by Sundwall8 Recent evidence however suggests that higher blood concentrations of pralidoxime are needed to antagonise the toxic effects of many pesticides and that a bolus loading infusion followed by a maintenance infusion would be the best regimen9 The WHO have proposed that patients receive around 30mgkg pralidoxime salt as a loading dose followed by an infusion of at least 8mgkghr roughly equivalent to 1-2 g bolus followed by 05 gh in a 50kg south Asian patient910 However no trials have yet been performed to determine whether such a regimen reduces morbidity and mortality in severely poisoned patients3 Since organophosphorus pesticides kill hundreds of thousands of people in rural Asia every year it is essential to determine whether it benefits or harms such poisoned patients
Our hospital has typically used a regimen of 1g q4h in organophosphorus poisoned patients but we were unconvinced about the effectiveness of this expensive drug since many patients required ventilation for 10 days We informally treated several patients with the WHO-recommended regimen but saw little benefit Since pralidoxime has a high therapeutic index we then decided to conduct a RCT with still higher doses ie to compare a 1 g infusion every hour q1h 24 gday with 1g every four hours q4h 6 gday after a 2 g loading dose to assess the effectiveness of high dose pralidoxime in organophosphorus poisoned patients
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