A Pilot Study Using Rocuronium to Prevent Intermediate Syndrome After Organophosphorus Insecticide Poisoning

Sponsor

University of Edinburgh (Other)

Overall Status

Completed

CT.gov ID

NCT02147054

Collaborator

University of Peradeniya (Other)

Enrollment

Location

Arms

Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Organophosphate pesticide poisoning causes close to 300 000 deaths per year worldwide. Many patients who ingest organophosphates require ventilation; of these patients approximately 50% die. Much of the mortality in these ventilated patients is secondary to intermediate syndrome. This is because OP pesticides inhibit acetylcholinesterase, causing an excess of acetylcholine at nerve synapses and the neuromuscular junction (NMJ). At the NMJ, the excess acetylcholine causes overstimulation and damage, which may lead to sudden respiratory arrest or prolonged ventilation and its associated complications.

The investigators believe that blocking these receptors using a neuromuscular blocking agent such as Rocuronium will protect the NMJ from damage and thus prevent intermediate syndrome and reduce number of intubated days and mortality.

In this pilot randomised controlled trial Rocuronium, a competitive nicotinic receptor antagonist, will be used to bind to the receptor at the neuromuscular junction and to block the effects of the accumulated acetylcholine. The effects of OP pesticide on cholinesterase in the blood will then be monitored and Rocuronium withdrawn using Sugammadex as the OP is eliminated from the body.

Condition or Disease	Intervention/Treatment	Phase
Organophosphate Poisoning	Drug: Rocuronium Drug: Sugammadex	Phase 2/Phase 3

Detailed Description

Primary outcome: Number of days intubated

Study Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Pilot Study - Assessing the Impact of Using a Neuromuscular Blocking Agent to Reduce Neuromuscular Junction Damage and Intermediate Syndrome in Organophosphorus (OP) Insecticide Poisoned Patients Requiring Ventilation

Study Start Date :

May 1, 2014

Actual Primary Completion Date :

Jul 1, 2016

Actual Study Completion Date :

Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Rocuronium with >95% inhibition IV Rocuronium to be given: Bolus dose of Rocuronium 0.3 mg/kg to achieve >95% inhibition as indicated by Train of Four monitoring Continuous infusion of 1.5 mg/kg/hr to maintain level of inhibition To continue until two rises in butyrylcholinesterase seen or for a maximum of 5 days	Drug: Rocuronium Other Names: Esmeron Drug: Sugammadex Effect of Rocuronium will be reversed at the appropriate time using Sugammadex 16mg/kg as a single dose which may be repeated once. Other Names: Bridion
Active Comparator: Rocuronium with 50% inhibition IV Rocuronium to be given: Bolus dose of Rocuronium 0.3 mg/kg to achieve 50% inhibition as indicated by Train of Four monitoring Continuous infusion of 1.5 mg/kg/hr to maintain level of inhibition To continue until two rises in butyrylcholinesterase seen or for a maximum of 5 days	Drug: Rocuronium Other Names: Esmeron Drug: Sugammadex Effect of Rocuronium will be reversed at the appropriate time using Sugammadex 16mg/kg as a single dose which may be repeated once. Other Names: Bridion
No Intervention: No Rocuronium No Rocuronium will be given

Arm

Intervention/Treatment

Active Comparator: Rocuronium with >95% inhibition

IV Rocuronium to be given: Bolus dose of Rocuronium 0.3 mg/kg to achieve >95% inhibition as indicated by Train of Four monitoring Continuous infusion of 1.5 mg/kg/hr to maintain level of inhibition To continue until two rises in butyrylcholinesterase seen or for a maximum of 5 days

Drug: Rocuronium

Other Names:

Esmeron

Drug: Sugammadex

Effect of Rocuronium will be reversed at the appropriate time using Sugammadex 16mg/kg as a single dose which may be repeated once.

Other Names:

Bridion

Active Comparator: Rocuronium with 50% inhibition

IV Rocuronium to be given: Bolus dose of Rocuronium 0.3 mg/kg to achieve 50% inhibition as indicated by Train of Four monitoring Continuous infusion of 1.5 mg/kg/hr to maintain level of inhibition To continue until two rises in butyrylcholinesterase seen or for a maximum of 5 days

Drug: Rocuronium

Other Names:

Esmeron

Drug: Sugammadex

Effect of Rocuronium will be reversed at the appropriate time using Sugammadex 16mg/kg as a single dose which may be repeated once.

Other Names:

Bridion

No Intervention: No Rocuronium

No Rocuronium will be given

Outcome Measures

Primary Outcome Measures

Number of intubated days [Upto 5 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

17 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Male or female
Age over 16
Clinical diagnosis of OP insecticide poisoning
Admission to Intensive Care Unit for Ventilation
Informed consent from family
Train of four measurement > 50%

Exclusion criteria:

Age 16 or under
Pregnant
Consent not obtained from patient or patient's family

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peradeniya Teaching Hospital	Peradeniya	Central Province	Sri Lanka

Sponsors and Collaborators

University of Edinburgh
University of Peradeniya

Investigators

Principal Investigator: Indika Gawarammana, MD FRCPE PhD, South Asian Clinical Toxicology Research Collaboration
Study Director: Michael Eddleston, MA PhD FRCP, University of Edinburgh
Study Director: Vasanti Pinto, MD FRCA FCARSCI, University of Peradeniya
Study Director: Vajira Weerasinghe, BDS MPhil PhD, University of Peradeniya