Organophosphate PoisoningPhase 3SalbutamolOPNCT02160548
Adding Nebulized Salbutamol to Intravenous Atropine and Oxygen in OP Poisoning
A Phase 3 study of Organophosphate Poisoning, run by Sylhet M.A.G.Osmani Medical College at 1 site in Bangladesh.
Trial summary
We hypothesize that salbutamol will speed removal of alveolar fluid compared to atropine alone in OP poisoned patients. We propose to compare the effect of two stat doses of nebulized salbutamol (2.5 mg; 5.0 mg), with nebulized saline placebo, in symptomatic patients receiving standard resuscitation with atropine… Read more about this study
- Who is it for?
- Ages 12 years and olderHealthy volunteers can take part
- Conditions the study is for
- Organophosphate Poisoning
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 1 siteBangladesh
- Study dates
- Apr 2015to Dec 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- age 12 yrs or older
- clinical features of OP poisoning
- requiring oxygen and atropine and give consent
Who cannot join
- age 11 yrs or younger
- no requirement for atropine
Trial locations and contacts
1 site in 1 country.
Bangladesh1 site
Sylhet M.A.G.Osmani Medical College Hospital
Sylhet, Sylhet Division, 3100
About this study
Official title: Effect of Adding Nebulized Salbutamol to Intravenous Atropine and Oxygen During Resuscitation of OP Pesticide Poisoned Patients
We hypothesize that salbutamol will speed removal of alveolar fluid compared to atropine alone in OP poisoned patients. We propose to compare the effect of two stat doses of nebulized salbutamol (2.5 mg; 5.0 mg), with nebulized saline placebo, in symptomatic patients receiving standard resuscitation with atropine, oxygen, and fluids after poisoning with OP pesticides. 25 patients will be randomised to each arm (total 75 patients). Primary outcome will be oxygen saturation's over the following 60 min during resuscitation. Secondary outcomes will include atropine dose administered, speed to stabilization, aspiration or pneumonia, intubation, tachydysrhythmias, and mortality. A positive outcome will result in design of a large definitive phase III study.
Read the detailed description
Pesticide self-poisoning kills over 300,000 people every year (1). Most deaths occur in rural Asia where widespread use of pesticides to boost food production allows easy access at stressful times. The WHO now recognizes pesticide poisoning to be the single most important global means of suicide (2) Amongst pesticides, organophosphorus (OP) and carbamate insecticides are of most concern, causing about 2/3 of deaths (1,3). These insecticides inhibit the enzyme acetylcholinesterase (AChE), producing an 'acute cholinergic crisis' with reduced consciousness, bradycardia, hypotension, and acute respiratory failure. On arrival at hospital, patients are resuscitated with atropine and, for OPs, an oxime AChE reactivator (4). Unfortunately, this treatment is often inadequate and many still die (5). A recent Bangladeshi RCT showed that rapid resuscitation of patients with atropine saves lives (6). This study compared a faster 'doubling dose' method of atropinisation with a standard bolus method during resuscitation. It reported quicker stabilisation and a 14% absolute reduction in mortality.
Rationale: Atropine only stops production of fluid and does not speed its removal from the lung. Therefore a treatment that increases removal, to complement atropine-induced cessation of production, could reduce fluid in the lungs and speed return effective oxygen exchange. A single nebulised dose of the beta-adrenergic agonist salbutamol may increase removal since it increases alveolar fluid removal via the epithelial sodium channel. A pilot clinical study is required to test the hypothesis and to provide data for powering a large phase III RCT.
Research question: Will addition of the beta-adrenergic agonist salbutamol to atropine during resuscitation improve oxygenation, reduce the need for atropine, and speed stabilisation?
Objectives:General Objectives: To test the efficacy of salbutamol at increasing oxygenation and speeding resuscitation.
Specific Objectives: To test whether salbutamol alters dose of atropine administered and incidence of tachydysrhythmias.
Total duration of the study will be one year and all patients aged 12 years or older with clinical features of OP/carbamate poisoning requiring oxygen and atropine will be enrolled. The study will be done in three arms.
- Conditions
- Organophosphate Poisoning
- Being tested
- Standard care, Standard care+ 2.5 mg Salbutamol, Standard care+ 5 mg Salbutamol
- Keywords
- Organophosphate, insectiside, Salbutamol, Atropine
- Medical subject headings
- Organophosphate Poisoning
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard careDrug
Also called Intravenous fluids, Intubation if necessary,, Mechanical ventilation if necessary (Engstrom Pro), Atropine (anti-muscarinic; G-Atropine)
Standard management for OP poisoning
Standard care+ 2.5 mg SalbutamolDrug
Also called Ventolin
Ventolin respiratory solution 2.5 mg
Standard care+ 5 mg SalbutamolDrug
Also called Ventolin
Ventolin respiratory solution 5 mg
| Study group | Role | What they receive |
|---|---|---|
| 'Standard care' | Placebo comparator | Standard care= Intravenous fluids, Oxygen by face mask, Intubation if necessary, Mechanical ventilation (Engstrom Pro by GE) if necessary, Cardiac monitor (Infunix IP4050), Atropine (anti-muscarinic drug; G-Atropine) by intravenous route, Pralidoxime (acetylcholinesterase reactivating oxime drug; PAM-A) by intravenous route. Receives: Drug: Standard care |
| 'Standard care+ 2.5 mg Salbutamol' | Experimental | Standard care+ 2.5 mg Salbutamol= Nebulized salbutamol (Ventolin respiratory solution) 2.5 mg stat and once only with standard care Receives: Drug: Standard care+ 2.5 mg Salbutamol |
| 'Standard care+ 5 mg Salbutamol' | Experimental | Standard care+ 5 mg Salbutamol= Nebulized salbutamol (Ventolin respiratory solution) 5 mg stat and once only with standard care Receives: Drug: Standard care+ 5 mg Salbutamol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement of oxygen saturation
Improvement of oxygen saturation from the base line to normal level after adding nebulized salbutamol to regular I/V atropine and oxygen therapy.
Measured: 60 minutes
Secondary outcomes (1)
Heart rate, respiratory rate and Blood pressure
Settlement of heart rate, respiratory rate and blood pressure to normal range after adding salbutamol to regular management.
Measured: 60 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2014 (estimated)
- Study startApr 2015
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Organophosphate PoisoningStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sylhet M.A.G.Osmani Medical College
- Sponsor type
- University, hospital or other
- Collaborators
- University of Edinburgh
- Responsible party
- Principal investigator, Dr. Fazle Rabbi Chowdhury, Sylhet M.A.G.Osmani Medical College
- Investigators
- Fazle R Chowdhury, FCPS, Principal investigator, Consultant, Medicine, Sylhet M.A.G.Osmani Medical Collge, Sylhet, BangladeshMichael Eddleston, PhD, Principal investigator, Professor of Clinical Toxicology, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02160548
- Sponsor's protocol ID
- Medicine SOMCH
- Acronym
- SalbutamolOP
- Status last verified
- Dec 2015
- First submitted
- 7 Jun 2014
- Last updated
- 29 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Abedin MJ, Sayeed AA, Basher A, Maude RJ, Hoque G, Faiz MA. Open-label randomized clinical trial of atropine bolus injection versus incremental boluses plus infusion for organophosphate poisoning in Bangladesh. J Med Toxicol. 2012 Jun;8(2):108-17. doi: 10.1007/s13181-012-0214-6.
PubMed 22351300Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008 Feb 16;371(9612):597-607. doi: 10.1016/S0140-6736(07)61202-1.
PubMed 17706760Gunnell D, Eddleston M, Phillips MR, Konradsen F. The global distribution of fatal pesticide self-poisoning: systematic review. BMC Public Health. 2007 Dec 21;7:357. doi: 10.1186/1471-2458-7-357.
PubMed 18154668Eddleston M. Patterns and problems of deliberate self-poisoning in the developing world. QJM. 2000 Nov;93(11):715-31. doi: 10.1093/qjmed/93.11.715.
PubMed 11077028
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Adding Nebulized Salbutamol to Intravenous Atropine and Oxygen During Resuscitation of OP Pesticide Poisoned Patients
- ClinicalTrials.gov ID
- NCT02160548
- Acronym / sponsor ID
- SalbutamolOP / Medicine SOMCH
- Conditions
- Organophosphate Poisoning
- Keywords
- Organophosphate, insectiside, Salbutamol, Atropine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Sylhet M.A.G.Osmani Medical CollegeUniversity, hospital or other
- Collaborators
- University of Edinburgh
- Study start
- Apr 2015
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 10 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
We hypothesize that salbutamol will speed removal of alveolar fluid compared to atropine alone in OP poisoned patients. We propose to compare the effect of two stat doses of nebulized salbutamol (2.5 mg; 5.0 mg), with nebulized saline placebo, in symptomatic patients receiving standard resuscitation with atropine, oxygen, and fluids after poisoning with OP pesticides. 25 patients will be randomised to each arm (total 75 patients). Primary outcome will be oxygen saturation's over the following 60 min during resuscitation. Secondary outcomes will include atropine dose administered, speed to stabilization, aspiration or pneumonia, intubation, tachydysrhythmias, and mortality. A positive outcome will result in design of a large definitive phase III study.
Detailed description
Pesticide self-poisoning kills over 300,000 people every year (1). Most deaths occur in rural Asia where widespread use of pesticides to boost food production allows easy access at stressful times. The WHO now recognizes pesticide poisoning to be the single most important global means of suicide (2) Amongst pesticides, organophosphorus (OP) and carbamate insecticides are of most concern, causing about 2/3 of deaths (1,3). These insecticides inhibit the enzyme acetylcholinesterase (AChE), producing an 'acute cholinergic crisis' with reduced consciousness, bradycardia, hypotension, and acute respiratory failure. On arrival at hospital, patients are resuscitated with atropine and, for OPs, an oxime AChE reactivator (4). Unfortunately, this treatment is often inadequate and many still die (5). A recent Bangladeshi RCT showed that rapid resuscitation of patients with atropine saves lives (6). This study compared a faster 'doubling dose' method of atropinisation with a standard bolus method during resuscitation. It reported quicker stabilisation and a 14% absolute reduction in mortality.
Rationale: Atropine only stops production of fluid and does not speed its removal from the lung. Therefore a treatment that increases removal, to complement atropine-induced cessation of production, could reduce fluid in the lungs and speed return effective oxygen exchange. A single nebulised dose of the beta-adrenergic agonist salbutamol may increase removal since it increases alveolar fluid removal via the epithelial sodium channel. A pilot clinical study is required to test the hypothesis and to provide data for powering a large phase III RCT.
Research question: Will addition of the beta-adrenergic agonist salbutamol to atropine during resuscitation improve oxygenation, reduce the need for atropine, and speed stabilisation?
Objectives:General Objectives: To test the efficacy of salbutamol at increasing oxygenation and speeding resuscitation.
Specific Objectives: To test whether salbutamol alters dose of atropine administered and incidence of tachydysrhythmias.
Total duration of the study will be one year and all patients aged 12 years or older with clinical features of OP/carbamate poisoning requiring oxygen and atropine will be enrolled. The study will be done in three arms.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 'Standard care' | Placebo comparator | Drug: Standard careStandard care= Intravenous fluids, Oxygen by face mask, Intubation if necessary, Mechanical ventilation (Engstrom Pro by GE) if necessary, Cardiac monitor (Infunix IP4050), Atropine (anti-muscarinic drug; G-Atropine) by intravenous route, Pralidoxime (acetylcholinesterase reactivating oxime drug; PAM-A) by intravenous route. |
| 'Standard care+ 2.5 mg Salbutamol' | Experimental | Drug: Standard care+ 2.5 mg SalbutamolStandard care+ 2.5 mg Salbutamol= Nebulized salbutamol (Ventolin respiratory solution) 2.5 mg stat and once only with standard care |
| 'Standard care+ 5 mg Salbutamol' | Experimental | Drug: Standard care+ 5 mg SalbutamolStandard care+ 5 mg Salbutamol= Nebulized salbutamol (Ventolin respiratory solution) 5 mg stat and once only with standard care |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- age 12 yrs or older
- clinical features of OP poisoning
- requiring oxygen and atropine and give consent
Key exclusion criteria (2 listed)
- age 11 yrs or younger
- no requirement for atropine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard careAlso: Intravenous fluids, Intubation if necessary,, Mechanical ventilation if necessary (Engstrom Pro), Atropine (anti-muscarinic; G-Atropine)Standard management for OP poisoning | Drug | 'Standard care' |
| Standard care+ 2.5 mg SalbutamolAlso: VentolinVentolin respiratory solution 2.5 mg | Drug | 'Standard care+ 2.5 mg Salbutamol' |
| Standard care+ 5 mg SalbutamolAlso: VentolinVentolin respiratory solution 5 mg | Drug | 'Standard care+ 5 mg Salbutamol' |
Primary outcome
Improvement of oxygen saturation
Time frame: 60 minutes
Improvement of oxygen saturation from the base line to normal level after adding nebulized salbutamol to regular I/V atropine and oxygen therapy.
1 secondary outcome
Heart rate, respiratory rate and Blood pressure
Time frame: 60 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2015.
- Background: PubMed 22351300Abedin MJ, Sayeed AA, Basher A, Maude RJ, Hoque G, Faiz MA. Open-label randomized clinical trial of atropine bolus injection versus incremental boluses plus infusion for organophosphate poisoning in Bangladesh. J Med Toxicol. 2012 Jun;8(2):108-17. doi: 10.1007/s13181-012-0214-6.
- Background: PubMed 17706760Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008 Feb 16;371(9612):597-607. doi: 10.1016/S0140-6736(07)61202-1.
- Background: PubMed 18154668Gunnell D, Eddleston M, Phillips MR, Konradsen F. The global distribution of fatal pesticide self-poisoning: systematic review. BMC Public Health. 2007 Dec 21;7:357. doi: 10.1186/1471-2458-7-357.
- Background: PubMed 11077028Eddleston M. Patterns and problems of deliberate self-poisoning in the developing world. QJM. 2000 Nov;93(11):715-31. doi: 10.1093/qjmed/93.11.715.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fazle R Chowdhury, FCPS principal investigator
Consultant, Medicine, Sylhet M.A.G.Osmani Medical Collge, Sylhet, Bangladesh
Michael Eddleston, PhD principal investigator
Professor of Clinical Toxicology, University of Edinburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study of Organophosphate Poisoning, run by Sylhet M.A.G.Osmani Medical College at 1 site in Bangladesh.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Bangladesh. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement of oxygen saturation (time frame: 60 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02160548, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2015.