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Adding Nebulized Salbutamol to Intravenous Atropine and Oxygen in OP Poisoning (SalbutamolOP)

Primary Purpose

Organophosphate Poisoning

Status
Completed
Phase
Phase 3
Locations
Bangladesh
Study Type
Interventional
Intervention
Standard care
Standard care+ 2.5 mg Salbutamol
Standard care+ 5 mg Salbutamol
Sponsored by
Sylhet M.A.G.Osmani Medical College
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Organophosphate Poisoning focused on measuring Organophosphate, insectiside, Salbutamol, Atropine

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • age 12 yrs or older
  • clinical features of OP poisoning
  • requiring oxygen and atropine and give consent

Exclusion Criteria:

  • age 11 yrs or younger
  • no requirement for atropine

Sites / Locations

  • Sylhet M.A.G.Osmani Medical College Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

'Standard care'

'Standard care+ 2.5 mg Salbutamol'

'Standard care+ 5 mg Salbutamol'

Arm Description

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.

Standard 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= Nebulized salbutamol (Ventolin respiratory solution) 5 mg stat and once only with standard care

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
June 7, 2014
Last Updated
December 28, 2015
Sponsor
Sylhet M.A.G.Osmani Medical College
Collaborators
University of Edinburgh
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1. Study Identification

Unique Protocol Identification Number
NCT02160548
Brief Title
Adding Nebulized Salbutamol to Intravenous Atropine and Oxygen in OP Poisoning
Acronym
SalbutamolOP
Official Title
Effect of Adding Nebulized Salbutamol to Intravenous Atropine and Oxygen During Resuscitation of OP Pesticide Poisoned Patients
Study Type
Interventional

2. Study Status

Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
April 2015 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sylhet M.A.G.Osmani Medical College
Collaborators
University of Edinburgh

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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, 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Organophosphate Poisoning
Keywords
Organophosphate, insectiside, Salbutamol, Atropine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
75 (Actual)

8. Arms, Groups, and Interventions

Arm Title
'Standard care'
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
'Standard care+ 2.5 mg Salbutamol'
Arm Type
Experimental
Arm Description
Standard care+ 2.5 mg Salbutamol= Nebulized salbutamol (Ventolin respiratory solution) 2.5 mg stat and once only with standard care
Arm Title
'Standard care+ 5 mg Salbutamol'
Arm Type
Experimental
Arm Description
Standard care+ 5 mg Salbutamol= Nebulized salbutamol (Ventolin respiratory solution) 5 mg stat and once only with standard care
Intervention Type
Drug
Intervention Name(s)
Standard care
Other Intervention Name(s)
Intravenous fluids, Intubation if necessary,, Mechanical ventilation if necessary (Engstrom Pro), Atropine (anti-muscarinic; G-Atropine), Pralidoxime (acetylcholinesterase reactivating oxime; PAM-A), Oxygen by face mask by intravenous route,
Intervention Description
Standard management for OP poisoning
Intervention Type
Drug
Intervention Name(s)
Standard care+ 2.5 mg Salbutamol
Other Intervention Name(s)
Ventolin
Intervention Description
Ventolin respiratory solution 2.5 mg
Intervention Type
Drug
Intervention Name(s)
Standard care+ 5 mg Salbutamol
Other Intervention Name(s)
Ventolin
Intervention Description
Ventolin respiratory solution 5 mg
Primary Outcome Measure Information:
Title
Improvement of oxygen saturation
Description
Improvement of oxygen saturation from the base line to normal level after adding nebulized salbutamol to regular I/V atropine and oxygen therapy.
Time Frame
60 minutes
Secondary Outcome Measure Information:
Title
Heart rate, respiratory rate and Blood pressure
Description
Settlement of heart rate, respiratory rate and blood pressure to normal range after adding salbutamol to regular management.
Time Frame
60 minutes
Other Pre-specified Outcome Measures:
Title
Atropine dose
Description
Requirement of total atropine dose until full atropinization (before put in to maintenance dose) after adding nebulized salbutamol
Time Frame
120 minutes

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: age 12 yrs or older clinical features of OP poisoning requiring oxygen and atropine and give consent Exclusion Criteria: age 11 yrs or younger no requirement for atropine
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fazle R Chowdhury, FCPS
Organizational Affiliation
Consultant, Medicine, Sylhet M.A.G.Osmani Medical Collge, Sylhet, Bangladesh
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michael Eddleston, PhD
Organizational Affiliation
Professor of Clinical Toxicology, University of Edinburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sylhet M.A.G.Osmani Medical College Hospital
City
Sylhet
ZIP/Postal Code
3100
Country
Bangladesh

12. IPD Sharing Statement

Citations:
PubMed Identifier
22351300
Citation
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.
Results Reference
background
PubMed Identifier
17706760
Citation
Eddleston 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.
Results Reference
background
PubMed Identifier
18154668
Citation
Gunnell 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.
Results Reference
background
PubMed Identifier
11077028
Citation
Eddleston 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.
Results Reference
background

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Adding Nebulized Salbutamol to Intravenous Atropine and Oxygen in OP Poisoning

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