Clinical trial NCT03925025: Effectiveness of Calcium Channel Blockade for OP and Carbamate Pesticide Poisoning
Official title: Effectiveness of Calcium Channel Blockade for Organophosphorus and Carbamate Pesticide Poisoning - an Open, Pragmatic, 3-arm RCT Repurposing Two Widely Available Licensed Medicines
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Anticholinesterase Insecticide Poisoning
Pesticide Poisoning
Lead sponsor: University of Edinburgh
Sponsor class: OTHER
Collaborators: name: Toxicology Society of Bangladesh
First posted: 2019-04-23
Enrollment: 3243
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates whether the addition of intravenous magnesium sulphate or nimodipine to standard therapy (supportive care plus for all patients atropine and, for OP insecticide poisoned patients, pralidoxime) benefits patients after acute anticholinesterase self-poisoning with OP or carbamate insecticides.


Eligibility criteria: Inclusion Criteria:

* Patients aged 16 years or older with suspected OP or carbamate insecticide self-poisoning admitted to medical wards with the cholinergic toxidrome requiring atropine.
* Diagnosis will be made on the basis of the cholinergic toxidrome clinical features (eg. small/pinpoint pupils, bronchorrhoea, sweating) or on the history of atropine administration with beneficial effect. The insecticide involved will be identified where possible from the history, the bottle brought in by the patient or relative, the patient/relative identifying the pesticide on a chart showing all locally available pesticides, and/or relatives sending a photo of the bottle by eg. WhatsApp.
* Patients who ingest combination products containing OP or carbamate insecticides will also be included.
* Inhibited blood cholinesterase activity as shown by routine clinical bedside test

Exclusion Criteria:

* Children aged \<16 years.
* Patients who do not require atropine and have not had it prior to presentation during this episode.
* Normal blood cholinesterase activity
* Self-reported known pregnancy (as per South Asian practice, no attempt will be made to formally test for pregnancy in the patients due to the issue of confidentiality in the acute care situation in these hospitals and the social consequences of an unexpected positive response)
* Known occupational and homicidal poisoning
* Past medical history of severely impaired renal function
* Hypersensitivity to magnesium and its salts
* Patients who have had a myocardial infarction or unstable angina in the last month
* Patients with traumatic subarachnoid haemorrhage
* Lack of informed consent (unaccompanied unconscious patients and others)

Primary outcomes:
measure: Mortality
timeFrame: through to hospital discharge, median 1 week
Secondary outcomes:
Other outcomes:
Locations:
city: Rājshāhi
country: Bangladesh
facility: Rajshahi Medical College Hospital
state: Rajshahi
city: Bogra
country: Bangladesh
facility: Shaheed Ziaur Rahman Medical College
state: Silimpur
city: Chittagong
country: Bangladesh
facility: Chattogram Medical College Hospital
city: Jessore
country: Bangladesh
facility: Jashore Medical College Hospital
city: Khulna
country: Bangladesh
facility: Khulna Medical College Hospital
city: Rangpur
country: Bangladesh
facility: Rangpur Medical College Hospital
city: Sylhet
country: Bangladesh
facility: Sylhet MAG Osmani Medical College Hospital
Study officials:
affiliation: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
name: Dr Fazle Rabbi Chowdhury, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brvar M, Chan MY, Dawson AH, Ribchester RR, Eddleston M. Magnesium sulfate and calcium channel blocking drugs as antidotes for acute organophosphorus insecticide poisoning - a systematic review and meta-analysis. Clin Toxicol (Phila). 2018 Aug;56(8):725-736. doi: 10.1080/15563650.2018.1446532. Epub 2018 Mar 20.