Condition category
Injury, Occupational Diseases, Poisoning
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status
Results overdue

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Prof Andrew Dawson


Contact details

Program Director
Visiting Professor of Medicine
South Asian Clinical Toxicology Research Collaboration (SACTRC)
University of Peradeniya
Sri Lanka
+94 (0)81 447 9822

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

A dose-finding phase II study of diazepam in adult patients presenting with signs or symptoms of acute organophosphate poisoning


Study hypothesis

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

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)

Study design

Dose escalation phase II randomised controlled trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Organophosphate poisoning


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



Phase II

Drug names


Primary outcome measure

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.

Secondary outcome measures

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.

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

Patients (aged 16 to 60 years, either sex) with symptomatic acute OP poisoning

Participant type


Age group




Target number of participants


Participant 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

Recruitment start date


Recruitment end date



Countries of recruitment

Sri Lanka

Trial participating centre

Program Director, Visiting Professor of Medicine
Sri Lanka

Sponsor information


South Asian Clinical Toxicology Research Collaboration (SACTRC) (Sri Lanka)

Sponsor details

c/o Professor Andrew Hamilton Dawson
Program Director
Visiting Professor of Medicine
University of Peradeniya
Sri Lanka
+94 (0)81 447 9822

Sponsor type

Research organisation



Funder type


Funder name

International Collaborative Research Grant:

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

The Wellcome Trust (UK) (grant ref: 071669)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Funder name

National Health and Medical Research Council (NHMRC) (Australia)

Alternative name(s)


Funding Body Type

government organisation

Funding Body Subtype

National government



Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes