To Study the Effects of Lipid Emulsion on Hemodynamics in Organophosphate Compound Poisoning

• ClinicalTrials.gov Identifier: NCT03564574
• Recruitment Status: Completed
• First Posted: June 21, 2018
• Last Update Posted: June 21, 2018
• Sponsor: Postgraduate Institute of Medical Education and Research
• Information provided by (Responsible Party): Bharath A. Chhabria, Postgraduate Institute of Medical Education and Research

Study Description

Brief Summary:

To Study the Effects of Lipid Emulsion on Hemodynamics in Organophosphate Compound Poisoning Objectives: To study the effect of administration of intravenous lipid emulsion on hemodynamic parameters, incidence of adverse effects in patients with organophosphate poisoning.

Background: Lipid emulsion has been used to revert toxicities of lipophilic drugs, toxins (especially lignocaine) and in critically ill patients. Though the safety has been established, the effect on hemodynamics in Organophosphate (OP) poisoned patients has never been studied. Hence this study is underway to fill those lacunae and evaluate the safety profile of lipid emulsion in organophosphate poisoned patients.

Methodology: The study is a prospective open label pilot study, which is underway at a tertiary care hospital in North India. Patients with history and clinical features of OP poisoning meeting the inclusion and exclusion parameters are being treated according to institutional protocols. Along with routine treatment a single dose of 20% lipid emulsion is being administered on admission to patients after obtaining consent. Patients are being followed up till discharge or death. Hemodynamic parameters and adverse effects following lipid emulsion administration are being studied over various intervals of time.

Condition or disease	Intervention/treatment	Phase
Organophosphate Poisoning	Combination Product: Lipid Emulsion	Phase 4

Detailed Description:

Methods A prospective open label pilot study was conducted with an aim to study the safety and effects of 20% lipid emulsion in OP compound poisoning. The objectives were to study the effects on hemodynamic parameters, the effect on morbidity, mortality and the occurrence of adverse events.

All patients, ≥ 13 years, with history of consumption of OP compound and clinical features of mild, moderate or severe OP compound poisoning as per the Peradeniya score (Table 1), admitted to the emergency department during the study period from September 2015 - December 2016 were included after written informed consent. Consent was obtained from the nearest kin if the presentation was with altered mental state. The recruitment began after approval from the institute's ethics committee.

Patients with chronic liver or kidney disease, history of acute or chronic pancreatitis in the past, those with combined poisoning with non OP compounds and asymptomatic patients were not included.

At presentation, detailed history was sought and subjects were examined for signs and symptoms of OP poisoning. Vital parameters (pulse rate, blood pressure, and respiratory rate) were noted. Blood samples were drawn for assessing baseline electrolytes, renal functions, haematological parameters and serum amylase. All patients received a single dose of 100mL of 20% lipid emulsion as an intra-venous infusion over 1 hour along with routine treatment as per institution protocols. Atropine was administered to patients by doubling dose method, which comprised of administering atropine starting from 2mg and to double the dose and administer till complete atropinization. Following this an infusion of 10-20 percent of the atropinizing dose was given every hour. In view of the controversial role of pralidoxime, it was not included in the study. The cases were followed up until recovery/death.

The patients were under observation for their vital signs, pupil size, fasciculation, respiratory crackles, amount of oral secretions and, if intubated, tracheal secretion. In addition they underwent monitoring of vital parameters every ten minutes during the course of lipid administration for the first thirty minutes followed by every fifteen minutes during the next 2 hours and every 2nd hourly thereafter.

Hemodynamic parameters, haematological, biochemical parameters, adverse effects and outcomes were compared at various intervals of time following administration of lipid emulsion, up to 72 hours, with those at the baseline; hemodynamic parameters were also compared with historic controls.

The primary outcome was to study the change in hemodynamic parameters (pulse rate, systolic blood pressure, mean arterial pressure and respiratory rate) after delivery of lipid emulsion in OP poisoned individuals up to 72 hours and compare any changes in the hemodynamic parameters with that of historic controls.

Secondary outcomes were to study the effects on case fatality (in-hospital until discharge or death), morbidity (duration of hospitalization, duration of mechanical ventilation, dose of atropine given) and the occurrence of complications including those related to lipid emulsion and hospital acquired infections.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: To Study the Effects of Lipid Emulsion on Hemodynamics in Organophosphate Compound Poisoning
• Actual Study Start Date: September 2015
• Actual Primary Completion Date: December 2016
• Actual Study Completion Date: December 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Study group; Inclusion criteria; History of consumption of OP compound.; Symptom complex consistent with OP poisoning; Age > 18 years; Informed consent from the patient or next kin. Exclusion criteria; History of combined poisoning with a non OP compound.; All other patients not fitting in the organophosphate symptom complex.; Patients with underlying liver and kidney disease.; History suggestive of acute pancreatitis in the past. All patients with history and clinical features of OP compound poisoning admitted to the emergency department in PGIMER during the study period, meeting the inclusion, exclusion criteria and who gave consent were enrolled in the study. Intervention : Administration of 100mL of 20% Lipid emulsion to all patients in the study group	Combination Product: Lipid Emulsion; All patients in the 'Study group' received a single dose of 100 ml of 20 percent Lipid emulsion as an infusion over 1 hour along with routine treatment as per institution protocols. Atropine was administered to patients by doubling dose method, which comprised of administering atropine starting from 2mg and to double the dose and administer till complete atropinization. Following this an infusion of 10 percent of the atropinizing dose was given every hour. Patients were evaluated using a standardized clinical interview, physical examination, laboratory tests.; Other Name: Intralipid 20 percent
No Intervention: Historic controls; The control arm The study group was compared with data of patients admitted for OP poisoning between the years 2013 and 2014 ( 2 calendar years), fulfilling the inclusion and exclusion criteria as stated above.

Outcome Measures

Primary Outcome Measures :

1. Significant change in pulse from baseline to 72 hours after admission [ Time Frame: Date of admission up to 72 hours ]

   The primary outcome was to study the change in

   1.Pulse (beats/min) after delivery of lipid emulsion in OP poisoned individuals at various intervals of time from time of admission to 72 hours after administration of lipid emulsion and compare the same data with historic controls

2. Significant change in systolic blood pressure from baseline to 72 hours after admission [ Time Frame: Date of admission up to 72 hours ]
   The primary outcome was to study the change in 2.Systolic blood pressure (mm Hg) after delivery of lipid emulsion in OP poisoned individuals at various intervals of time from time of admission to 72 hours after administration of lipid emulsion and compare the same data with historic controls
3. Significant change in oxygen arterial saturation from baseline to 72 hours after admission [ Time Frame: Date of admission up to 72 hours ]
   Change in arterial oxygen saturation (SpO2) in percentage
4. Adverse effects [ Time Frame: Date of admission until discharge/death of subjects up to 1 month ]
   Incidence of adverse reactions in percentage
5. Significant change in diastolic blood pressure from baseline to 72 hours after admission [ Time Frame: Date of admission up to 72 hours ]
   The primary outcome was to study the change in 5. Diastolic blood pressure (mm Hg) after delivery of lipid emulsion in OP poisoned individuals at various intervals of time from time of admission to 72 hours after administration of lipid emulsion and compare the same data with historic controls
6. Significant change in mean arterial pressure from baseline to 72 hours after admission [ Time Frame: Date of admission up to 72 hours ]
   The primary outcome was to study the change in 6. Mean arterial pressure (mm Hg) after delivery of lipid emulsion in OP poisoned individuals at various intervals of time from time of admission to 72 hours after administration of lipid emulsion and compare the same data with historic controls

Secondary Outcome Measures :

1. Effect on case fatality and morbidity [ Time Frame: Admission to the hospital till time of discharge up to 1 month ]

   Secondary outcomes were to study the effects on

   1. All cause mortality (in-hospital until discharge or death), that is the case fatality and morbidity in terms of duration of hospitalization in days, duration of mechanical ventilation in days, dose of atropine given in milligram an The data was compared with historic controls

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria

1. History of consumption of OP compound.
2. Symptom complex consistent with OP poisoning
3. Age > 18 years
4. Informed consent from the patient or next kin.

Exclusion criteria

1. History of combined poisoning with a non OP compound.
2. All other patients not fitting in the organophosphate symptom complex.
3. Patients with underlying liver and kidney disease.
4. History suggestive of acute pancreatitis in the past.

Contacts and Locations

Locations

India

Pgimer

Chandigarh, India, 160012

Sponsors and Collaborators

Postgraduate Institute of Medical Education and Research

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chhabria BA, Bhalla A, Shafiq N, Kumar S, Dhibar DP, Sharma N. Lipid emulsion for acute organophosphate insecticide poisoning - a pilot observational safety study. Clin Toxicol (Phila). 2019 May;57(5):318-324. doi: 10.1080/15563650.2018.1520997. Epub 2018 Oct 11.

• Responsible Party: Bharath A. Chhabria, Doctor, Postgraduate Institute of Medical Education and Research
• ClinicalTrials.gov Identifier: NCT03564574
• Other Study ID Numbers: bharath_thesis
• First Posted: June 21, 2018
• Last Update Posted: June 21, 2018
• Last Verified: June 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Poisoning; Organophosphate Poisoning; Chemically-Induced Disorders; Soybean oil, phospholipid emulsion; Fat Emulsions, Intravenous; Parenteral Nutrition Solutions; Pharmaceutical Solutions