What is the safe dose of diazepam that can be used as an effective adjunct treatment in organophosphate poisoning?

ISRCTN	ISRCTN64727867
DOI	https://doi.org/10.1186/ISRCTN64727867
Protocol serial number	N/A
Sponsor	South Asian Clinical Toxicology Research Collaboration (SACTRC) (Sri Lanka)
Funders	International Collaborative Research Grant:, The Wellcome Trust (UK) (grant ref: 071669), National Health and Medical Research Council (NHMRC) (Australia)

Submission date: 23/01/2009
Registration date: 28/01/2009
Last edited: 28/01/2009

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

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Andrew Dawson
Scientific

Program Director, Visiting Professor of Medicine
South Asian Clinical Toxicology Research Collaboration (SACTRC)
University of Peradeniya
Peradeniya
20400
Sri Lanka

Phone	+94 (0)81 447 9822
Email	adawson@sactrc.org

Study information

Primary study design	Interventional
Study design	Dose escalation phase II randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A dose-finding phase II study of diazepam in adult patients presenting with signs or symptoms of acute organophosphate poisoning
Study objectives	What is the safe and effective diazepam regimen in organophosphate (OP) poisoning that could: 1. Reduce mortality and/or the need for ventilation 2. Provide moderate sedation 3. Not cause symptomatic adverse effects on blood pressure
Ethics approval(s)	1. Sri Lanka Medical Association Ethical Committee gave approval on the 13th January 2006 (ref: 05-023) 2. University of Peradeniya, Faculty of Medicine, Ethical Review Committee gave approval on the 16th November 2007 (ref: 2006/EC/40) 3. Australian Nation University Ethics Committee gave approval on 15th February 2006 (ref: 2005/354)
Health condition(s) or problem(s) studied	Organophosphate poisoning
Intervention	The dose escalation relates to a course of diazepam. The first three doses are single doses of 2.5 mg, 5 mg, and 10 mg. The fourth group will receive a dose of 10 mg - and then two subsequent doses of 5 mg at 6 hour intervals. The first cohort of patients (2 controls and 6 diazepam) would receive a loading dose of 2.5 mg. If this is tolerated the next cohort would receive the next highest loading dose (i.e. 5 mg) and so on. If any patients do not tolerate a dose then the trial will be terminated at that dose level. Diazepam would be administered by a slow infusion with the total dose being given over 30 minutes. The study will be nested into observational trials being conducted in the same hospitals. This standard treatment is determined by the attending physician who maintains clinical responsibility for all patients. While there may be some minor variation between hospitals current care consists of patient resuscitation, gastrointestinal decontamination when indicated, atropinisation and the use of pralidoxime (typically one gram every six hours). All treatment is recorded by the research team. This intervention represents an added treatment to the existing standard of care.
Intervention type	Drug
Phase	Phase II
Drug / device / biological / vaccine name(s)	Diazepam
Primary outcome measure(s)	Number of patients that exhibit possible adverse effects such as: 1. A decrease in level of consciousness (measured using the Glasgow Coma Scale) 2. Respiratory depression (measured by a respiratory rate less than 10, and a tidal volume of less than 180 ml/breath using a Wright's spirometer) 3. Hypotension (blood pressure [BP] less than 90/60 mmHg, or a drop of greater than 20 mmHg systolic in a normotensive patient, i.e. systolic BP less than 140 mmHg) Monitored every 15 minutes for the first 2 hours of administration of diazepam or placebo and then monitored hourly for the next 3 hours, and thereafter 4-hourly if the patient is clinically well, or more frequently if there are any clinical concerns.
Key secondary outcome measure(s)	1. Number of patients that required ventilation 2. Changes in electroencephalogram (EEG), arterial blood gas (ABG), tidal volume and capnography 3. Patients who had seizures or died Monitored at baseline, 1 hour, 12 hours, 24 hours and daily. Continuous capnographic recording shall also be performed.
Completion date	09/06/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	32
Key inclusion criteria	Patients (aged 16 to 60 years, either sex) with symptomatic acute OP poisoning
Key exclusion criteria	1. Patients who do not consent 2. Aged less than 16 years or greater than 60 years 3. Pregnant women and lactating mothers 4. Unavailability of ventilator 5. Patients in whom endotracheal (ET) intubation is likely to be difficult 6. Have a Glasgow Coma Score (GCS) less than 12 at the time of recruitment 7. Ingested benzodiazepines in addition to OP 8. Have established renal or hepatic failure 9. Have indications for therapeutic diazepam 10. Patients who have respiratory failure requiring ventilatory support 11. Patients who have systolic blood pressure of less than 90 mmHg within 2 hours of administration of diazepam
Date of first enrolment	01/11/2008
Date of final enrolment	09/06/2009

Locations

Countries of recruitment

Sri Lanka

Study participating centre

Program Director, Visiting Professor of Medicine

Peradeniya
20400
Sri Lanka

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes