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|Acute organophosphate pesticide poisoning in Sri Lanka: management, complications and pharmacogenetics|
|Public title||Acute organophosphate pesticide poisoning in Sri Lanka: management, complications and pharmacogenetics|
|Serial number at source||GR063560|
We propose to carry out a double-blind randomised controlled trial (RCT) of pralidoxime in adult patients presenting with a history and symptoms of organophosphate (OP) poisoning. Primary outcome will be in-hospital mortality; secondary outcomes will include the occurrence of serious complications (respiratory arrest, intermediate syndrome) and time requiring assisted ventilation. Analysis will be on an intention-to-treat basis; the effects of reported time to treatment after poisoning and status on admission will also be assessed.
This RCT will be nested into a study of activated charcoal in unselected cases of poisoning (ISRCTN02920054). All investigations and outcome assessments for ISRCTN02920054 will suffice for this RCT. Extra blood samples will not be taken from patients in this RCT.
The main hypothesis is that the pralidoxime will reduce the case fatality rate from 25% to 19%, hence the primary comparison will be pralidoxime versus placebo. The dimethyl versus diethyl state of the OPs is thought to be fundamental for the effectiveness of oximes in OP poisoning. Dimethylated acetylcholinesterase ages quickly such that oximes do not work in vitro more than 12 hours post-ingestion; in contrast, diethylated acetylcholinesterase age slower so that oximes in vitro work for three to four days post-ingestion. Therefore, once the dimethyl/diethyl status has been retrospectively determined, the analysis will be repeated separating the two groups of OP agents.
It is possible that the oxime, if effective in reducing case fatality rates, will be more effective the earlier it is started. Therefore we will assess the trends in clinical effectiveness according to time post-ingestion to start of therapy. This will be repeated once dimethyl compounds have been distinguished from diethyl compounds. We also want to determine whether treatment should be started irrespective of severity. We will therefore assess trends in case fatality rates across a gradient of severity.
We hypothesise that pralidoxime treatment will prevent the occurrence of the intermediate syndrome; this will therefore be an important secondary outcome. This analysis will be repeated once retrospective toxicological analysis has separated dimethyl compounds from diethyl compounds.
Subgroup analyses are planned to look at the consistency of treatment effect across different types of pesticide, i.e. dimethylated versus diethylated OP pesticides, and for locally common pesticides. A further subgroup analysis will be performed according to the presence of reactivatable acetylcholinesterase before treatment, following retrospective assays of ex-vivo reactivatability.
Please note that as of 14/12/2007 the anticipated end date of this trial has been extended to 01/07/2007. The intial anticipated end date of this trial was 31/05/2007.
|Lay summary||Not provided at time of registration|
|Ethics approval||Not provided at time of registration|
|Study design||Randomised controlled trial|
|Countries of recruitment||Sri Lanka|
|Disease/condition/study domain||Acute organophosphate self-poisoning|
|Participants - inclusion criteria||All patients (aged 14 years of above, either sex) presenting with history and signs of acute organophosphate self-poisoning in selected Sri Lankan hospitals, requiring atropine.|
|Participants - exclusion criteria||
We hope to recruit all patients admitted to the medical wards with a history of acute poisoning and symptoms and signs of organophosphate poisoning, except for those:
1. Under the age of 14 years
2. Known to be pregnant
3. Have previously received Pralidoxime
4. Patients under the age of 16 or unconscious, who are present without relatives
|Anticipated start date||01/05/2004|
|Anticipated end date||01/07/2007|
|Status of trial||Completed|
|Patient information material|
|Target number of participants||1500 - recruitment ends on the 1st May 2007|
|Interventions||Atropine and pralidoxime chloride (2 g stat followed by 500 mg/h for up to seven days) versus atropine and saline placebo.|
|Primary outcome measure(s)||All-cause mortality at hospital discharge|
|Secondary outcome measure(s)||
1. Percentage of patients requiring intubation
2. Time requiring ventilation
3. Percentage of patients developing the intermediate syndrome (cranial nerve palsies and/or proximal weakness, without distal weakness, after resolution of the cholinergic crisis)
|Sources of funding||The Wellcome Trust (UK) (grant ref: 063560) - Tropical Medicine Programme|
|Publications||2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19564902|
|Contact name||Mr Michael Eddleston|
Scottish Poisons Information Bureau
51 Little France Crescent
|Tel||+44 (0)131 242 1383|
|Fax||+44 (0)131 242 1387|
|Sponsor||University of Oxford (UK)|
|Tel||+44 (0)1865 270000|
|Date ISRCTN assigned||29/07/2002|