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 |
| Secondary identifying numbers | N/A |
- 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
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 |
|---|---|
| adawson@sactrc.org |
Study information
| Study design | Dose escalation phase II randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Diazepam |
| 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 study start date | 01/11/2008 |
| Completion date | 09/06/2009 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 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
20400
Sri Lanka
Sponsor information
South Asian Clinical Toxicology Research Collaboration (SACTRC) (Sri Lanka)
Research organisation
Research organisation
c/o Professor Andrew Hamilton Dawson
Program Director, Visiting Professor of Medicine
University of Peradeniya
Peradeniya
20400
Sri Lanka
| Phone | +94 (0)81 447 9822 |
|---|---|
| adawson@sactrc.org | |
| Website | http://www.sactrc.org |
"ROR" |
https://ror.org/04z435g27 |
Funders
Funder type
Charity
International Collaborative Research Grant:
No information available
The Wellcome Trust (UK) (grant ref: 071669)
No information available
National Health and Medical Research Council (NHMRC) (Australia)
Government organisation / National government
Government organisation / National government
- Alternative name(s)
- NHMRC
- Location
- Australia
Results and Publications
| Intention to publish date | |
|---|---|
| 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 |
