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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02160548
Recruitment Status : Completed
First Posted : June 10, 2014
Last Update Posted : December 29, 2015
University of Edinburgh
Information provided by (Responsible Party):
Dr. Fazle Rabbi Chowdhury, Sylhet M.A.G.Osmani Medical College

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.

Condition or disease Intervention/treatment Phase
Organophosphate Poisoning Drug: Standard care Drug: Standard care+ 2.5 mg Salbutamol Drug: Standard care+ 5 mg Salbutamol Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of Adding Nebulized Salbutamol to Intravenous Atropine and Oxygen During Resuscitation of OP Pesticide Poisoned Patients
Study Start Date : April 2015
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

Arm Intervention/treatment
Placebo Comparator: 'Standard care'
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.
Drug: Standard care
Standard management for OP poisoning
Other Names:
  • 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,

Experimental: 'Standard care+ 2.5 mg Salbutamol'
Standard care+ 2.5 mg Salbutamol= Nebulized salbutamol (Ventolin respiratory solution) 2.5 mg stat and once only with standard care
Drug: Standard care+ 2.5 mg Salbutamol
Ventolin respiratory solution 2.5 mg
Other Name: Ventolin

Experimental: 'Standard care+ 5 mg Salbutamol'
Standard care+ 5 mg Salbutamol= Nebulized salbutamol (Ventolin respiratory solution) 5 mg stat and once only with standard care
Drug: Standard care+ 5 mg Salbutamol
Ventolin respiratory solution 5 mg
Other Name: Ventolin

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Heart rate, respiratory rate and Blood pressure [ Time Frame: 60 minutes ]
    Settlement of heart rate, respiratory rate and blood pressure to normal range after adding salbutamol to regular management.

Other Outcome Measures:
  1. Atropine dose [ Time Frame: 120 minutes ]
    Requirement of total atropine dose until full atropinization (before put in to maintenance dose) after adding nebulized salbutamol

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02160548

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Sylhet M.A.G.Osmani Medical College Hospital
Sylhet, Bangladesh, 3100
Sponsors and Collaborators
Sylhet M.A.G.Osmani Medical College
University of Edinburgh
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Principal Investigator: Fazle R Chowdhury, FCPS Consultant, Medicine, Sylhet M.A.G.Osmani Medical Collge, Sylhet, Bangladesh
Principal Investigator: Michael Eddleston, PhD Professor of Clinical Toxicology, University of Edinburgh
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Responsible Party: Dr. Fazle Rabbi Chowdhury, Consultant, Medicine, Sylhet M.A.G.Osmani Medical College Identifier: NCT02160548    
Other Study ID Numbers: Medicine SOMCH
First Posted: June 10, 2014    Key Record Dates
Last Update Posted: December 29, 2015
Last Verified: December 2015
Keywords provided by Dr. Fazle Rabbi Chowdhury, Sylhet M.A.G.Osmani Medical College:
Organophosphate, insectiside, Salbutamol, Atropine
Additional relevant MeSH terms:
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Organophosphate Poisoning
Chemically-Induced Disorders
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adjuvants, Anesthesia
Anti-Arrhythmia Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Protective Agents
Cholinesterase Reactivators