Adding Nebulized Salbutamol to Intravenous Atropine and Oxygen in OP Poisoning

Organophosphate Poisoning Clinical Trial

— SalbutamolOP  

Official title:

Effect of Adding Nebulized Salbutamol to Intravenous Atropine and Oxygen During Resuscitation of OP Pesticide Poisoned Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02160548
• Other study ID #: Medicine SOMCH
• Status: Completed
• Phase: Phase 3
• First received: June 7, 2014
• Last updated: December 28, 2015
• Start date: April 2015
• Est. completion date: December 2015

Study information

• Verified date: December 2015
• Source: Sylhet M.A.G.Osmani Medical College
• Contact: n/a
• Is FDA regulated: No
• Health authority: Bangladesh: Ethical Review Committee
• Study type: Interventional

Clinical 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, 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 12 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Organophosphate Poisoning
• Poisoning

Intervention

Drug:
• Standard care
Standard management for OP poisoning
• Standard care+ 2.5 mg Salbutamol
Ventolin respiratory solution 2.5 mg
• Standard care+ 5 mg Salbutamol
Ventolin respiratory solution 5 mg

Locations

Country	Name	City	State
Bangladesh	Sylhet M.A.G.Osmani Medical College Hospital	Sylhet

Sponsors (2)

Lead Sponsor	Collaborator
Sylhet M.A.G.Osmani Medical College	University of Edinburgh

Country where clinical trial is conducted

Bangladesh, 

References & Publications (4)

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. — View Citation

Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008 Feb 16;371(9612):597-607. Review. — View Citation

Eddleston M. Patterns and problems of deliberate self-poisoning in the developing world. QJM. 2000 Nov;93(11):715-31. Review. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Atropine dose	Requirement of total atropine dose until full atropinization (before put in to maintenance dose) after adding nebulized salbutamol	120 minutes	Yes
Primary	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.	60 minutes	Yes
Secondary	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.	60 minutes	Yes