Adding Nebulized Salbutamol to Intravenous Atropine and Oxygen in OP Poisoning

NCT ID: NCT02160548

Last Updated: 2015-12-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2015-12-31

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.

Conditions

Organophosphate Poisoning

Keywords

Organophosphate, insectiside, Salbutamol, Atropine

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

'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.

Group Type: PLACEBO_COMPARATOR

Standard care

Intervention Type: DRUG

Standard management for OP poisoning

'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

Group Type: EXPERIMENTAL

Standard care+ 2.5 mg Salbutamol

Intervention Type: DRUG

Ventolin respiratory solution 2.5 mg

'Standard care+ 5 mg Salbutamol'

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

Group Type: EXPERIMENTAL

Standard care+ 5 mg Salbutamol

Intervention Type: DRUG

Ventolin respiratory solution 5 mg

Interventions

Standard care

Standard management for OP poisoning

Intervention Type: DRUG

Standard care+ 2.5 mg Salbutamol

Ventolin respiratory solution 2.5 mg

Intervention Type: DRUG

Standard care+ 5 mg Salbutamol

Ventolin respiratory solution 5 mg

Intervention Type: DRUG

Other Intervention 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,; Ventolin; Ventolin

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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Edinburgh

OTHER

Sponsor Role: collaborator

Sylhet M.A.G.Osmani Medical College

OTHER

Sponsor Role: lead

Responsible Party

Dr. Fazle Rabbi Chowdhury

Consultant, Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fazle R Chowdhury, FCPS

Role: PRINCIPAL_INVESTIGATOR

Consultant, Medicine, Sylhet M.A.G.Osmani Medical Collge, Sylhet, Bangladesh

Michael Eddleston, PhD

Role: PRINCIPAL_INVESTIGATOR

Professor of Clinical Toxicology, University of Edinburgh

Locations

Sylhet M.A.G.Osmani Medical College Hospital

Sylhet, Sylhet Division, Bangladesh

Countries

Bangladesh

References

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.

Reference Type: BACKGROUND

PMID: 22351300 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17706760 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18154668 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11077028 (View on PubMed)

Other Identifiers

Medicine SOMCH

Identifier Type: -

Identifier Source: org_study_id