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Acute organophosphate pesticide poisoning in Sri Lanka: management, complications and pharmacogenetics
ClinicalTrials.gov identifier
Public title Acute organophosphate pesticide poisoning in Sri Lanka: management, complications and pharmacogenetics
Scientific title
Acronym N/A
Serial number at source GR063560
Study hypothesis 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
Trial website
Publications 2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19564902
Contact name Mr  Michael  Eddleston
  Address Scottish Poisons Information Bureau
Royal Infirmary
51 Little France Crescent
  City/town Edinburgh
  Zip/Postcode EH16 4SA
  Country United Kingdom
  Tel +44 (0)131 242 1383
  Fax +44 (0)131 242 1387
  Email eddlestonm@yahoo.com
Sponsor University of Oxford (UK)
  Address University Offices
Wellington Square
  City/town Oxford
  Zip/Postcode OX1 2JD
  Country United Kingdom
  Tel +44 (0)1865 270000
  Email Research.services@admin.ox.ac.uk
  Sponsor website http://www.ox.ac.uk/
Date applied 29/07/2002
Last edited 21/03/2013
Date ISRCTN assigned 29/07/2002