Acute organophosphate pesticide poisoning in Sri Lanka: management, complications and pharmacogenetics
ISRCTN | ISRCTN55264358 |
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DOI | https://doi.org/10.1186/ISRCTN55264358 |
Secondary identifying numbers | GR063560 |
- Submission date
- 29/07/2002
- Registration date
- 29/07/2002
- Last edited
- 17/02/2015
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Injury, Occupational Diseases, Poisoning
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Mr Michael Eddleston
Scientific
Scientific
Scottish Poisons Information Bureau
Royal Infirmary
51 Little France Crescent
Edinburgh
EH16 4SA
United Kingdom
Phone | +44 (0)131 242 1383 |
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eddlestonm@yahoo.com |
Study information
Study design | Randomised controlled trial |
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Primary study design | Interventional |
Secondary study design | Randomised controlled trial |
Study setting(s) | Hospital |
Study type | Treatment |
Scientific title | Acute organophosphate pesticide poisoning in Sri Lanka: management, complications and pharmacogenetics |
Study objectives | 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. On 14/12/2007 the overall trial end date was changed from 31/05/2007 to 01/07/2007. |
Ethics approval(s) | Not provided at time of registration |
Health condition(s) or problem(s) studied | Acute organophosphate self-poisoning |
Intervention | Atropine and pralidoxime chloride (2 g stat followed by 500 mg/h for up to seven days) versus atropine and saline placebo. |
Intervention type | Drug |
Pharmaceutical study type(s) | |
Phase | Not Applicable |
Drug / device / biological / vaccine name(s) | Atropine, pralidoxime chloride |
Primary outcome measure | All-cause mortality at hospital discharge |
Secondary outcome measures | 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) |
Overall study start date | 01/05/2004 |
Completion date | 01/07/2007 |
Eligibility
Participant type(s) | Patient |
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Age group | Adult |
Sex | Both |
Target number of participants | 1500 |
Key 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. |
Key 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 |
Date of first enrolment | 01/05/2004 |
Date of final enrolment | 01/05/2007 |
Locations
Countries of recruitment
- Scotland
- Sri Lanka
- United Kingdom
Study participating centre
Scottish Poisons Information Bureau
Edinburgh
EH16 4SA
United Kingdom
EH16 4SA
United Kingdom
Sponsor information
University of Oxford (UK)
University/education
University/education
University Offices
Wellington Square
Oxford
OX1 2JD
England
United Kingdom
Phone | +44 (0)1865 270000 |
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Research.services@admin.ox.ac.uk | |
Website | http://www.ox.ac.uk/ |
https://ror.org/052gg0110 |
Funders
Funder type
Charity
Wellcome Trust
Private sector organisation / International organizations
Private sector organisation / International organizations
- Location
- United Kingdom
Results and Publications
Intention to publish date | |
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Individual participant data (IPD) Intention to share | No |
IPD sharing plan summary | Not provided at time of registration |
Publication and dissemination plan | Not provided at time of registration |
IPD sharing plan |
Study outputs
Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
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Results article | results | 30/06/2009 | Yes | No |