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Is There an Adverse Drug Reaction Between Renin-Angiotensin System Blockade and Inhaled Anesthetics

Primary Purpose

Hypertension

Status
Unknown status
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Sevoflurane/oxygen/air/nitrous oxide
Sponsored by
Lawson Health Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Hypertension focused on measuring Hypertension, Sevoflurane, Inhaled Anesthetic, Angiotensin Converting Enzyme Inhibitor, Angiotensin II Receptor Blocking Agent

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • age over 40
  • composite head and neck tumor resection
  • treated hypertension
  • hypertension medications taken on morning of surgery (except diuretics)

Exclusion Criteria:

  • patient refusal
  • age less than 40 or over 80 years
  • combined surgical procedures
  • emergency surgery
  • Left ventricular ejection fraction less than 50 per cent
  • calculated creatinine clearance less than 60 mL per minute

Sites / Locations

  • London Health Sciences Centre - Victoria CampusRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Other

Other

Arm Label

Angiotensin Converting Enzyme Exposed

Angiotensin Receptor Blocker Exposed

Non ACE/ARB Exposed

Arm Description

Sevoflurane/oxygen/air/nitrous oxide Hypertensive patients exposed to Angiotensin Converting Enzyme Inhibitors (ACE Inhibitors)will make up this arm. Preoperative Exposure to any of the following Angiotensin Converting Enzyme Inhibitors Enalapril (Vasotec/Renitec) Ramipril (Altace/Prilace/Ramace/Ramiwin/Triatec/Tritace) Quinapril (Accupril) Perindopril (Coversyl/Aceon) Lisinopril (Listril/Lopril/Novatec/Prinivil/Zestril) Benazepril (Lotensin) Imidapril (Tanatril) Zofenopril (Zofecard) Trandolapril (Mavik/Odrik/Gopten) Fosinopril (Fositen/Monopril)

Sevoflurane/oxygen/air/nitrous oxide Hypertensive patients exposed to Angiotensin Receptor Blocking Agents (ARBs). Preoperative Exposure to any of the following Angiotensin II Receptor Blocking Agents Losartan(Cozaar) Candesartan (Atacand) Valsartan (Diovan) Irbesartan (Avapro) Telmisartan (Micardis) Eprosartan (Teveten) Olemisartan (Benicar) Azilsartan (Edarbi)

Sevoflurane/oxygen/air/nitrous oxide Hypertensive patients not exposed to angiotensin converting enzyme inhibitors or Angiotensin receptor blocking agents will be put into this arm.

Outcomes

Primary Outcome Measures

Systemic Vascular Resistance Index (SVRI)
A calculated hemodyamic parameter that assesses the resistance the heart faces to the forward flow of blood. Corrected for body surface area. SVRI = (cardiac output/blood pressure)/body surface area.

Secondary Outcome Measures

Heart Rate
number of heart beats per minute
Systolic Blood Pressure
force of blood flow (measured in mmHg)
Diastolic Blood Pressure
force of blood flow (measured in mmHg)
Central Venous Pressure
force of blood flow returning to the heart (measured in mmHg)
Cardiac Output (CO)
Calculated volume of blood flow in Litres per minute(measured in mmHg). Cardiac Output = mean arterial pressure/systemic vascular resistance.
Cardiac Index (CI)
Calculated volume of blood flow in Litres per minute(measured in mmHg/m2), corrected for body surface area. Cardiac Output = (mean arterial pressure/systemic vascular resistance)/body surface area.
Stroke Volume Varriation
Calculated variation in stroke volume between heart beats (blood pressure = stroke volume x rate x systemic vascular resisitance).measured in real time throughout experiment, and at each anesthetic concentration
Systemic Vascular Resistance
A calculated parameter reflecting the resistance the heart faces to the forward flow of blood. Not corrected for body surface area. SVR = cardiac ouptut / blood pressure. Measured at each concentraion of inhaled anesthetic

Full Information

First Posted
October 1, 2012
Last Updated
August 22, 2017
Sponsor
Lawson Health Research Institute
Collaborators
University of Western Ontario, Canada
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1. Study Identification

Unique Protocol Identification Number
NCT01715584
Brief Title
Is There an Adverse Drug Reaction Between Renin-Angiotensin System Blockade and Inhaled Anesthetics
Official Title
Is There an Adverse Drug Reaction Between Renin-Angiotensin System Blockade and Inhaled Anesthetics? - A Pilot Study. Optional Deoxyribo-Nucleic Acid Donation for the Study of Hypertension.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Unknown status
Study Start Date
July 2012 (undefined)
Primary Completion Date
December 31, 2019 (Anticipated)
Study Completion Date
December 31, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Lawson Health Research Institute
Collaborators
University of Western Ontario, Canada

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
It is controversial whether or not patients whose Renin Angiotensin System is blocked for the treatment of hypertension suffer increased risk when undergoing surgery and anaesthesia. The investigators wish to test the hypothesis: Blockade of the Renin Angiotensin System causes altered dose response under general anaesthesia in a dose dependant manner. The investigators wish to look for altered responses across the usual anaesthetic dosing range as measured by blood pressure and heart responses.
Detailed Description
There has been mixed results in retrospective studies examining the effects of renin angiotensin blockade for the treatment of cardiovascular disease and post operative outcomes. Studies done in high risk patients have shown increased risk of death if patients are exposed to angiotensin converting enzyme inhibitors and angiotensin blocking agents. The hypothesis is that patients exposed to medications that block the renin angiotensin system have altered dose response (a type of adverse drug reaction) to inhaled anaesthetic agents in a dose dependant manner as measured by cardiovascular response, specifically systemic vascular resistance index. This is a pilot study of hypertensive patients undergoing anaesthesia and composite head and neck surgery. The patients will be separated into three groups: Angiotensin converting enzyme inhibitor exposed, Angiotensin Receptor Blocking Agent exposed, and any other treated hypertension. Following separation into groups based upon preoperative medication exposures each group will be randomized to determine the order in which two types of inhaled anaesthetics are administered. Each subject will be randomized to receive either Sevoflurane/air/oxygen first or Sevoflurane/50 per cent nitrous oxide/oxygen second or vice versa. The dose of the anaesthetic will be adjusted across the dosing range from 0.8 MAC (minimum alveolar concentration) to 1.6 MAC in steps of 0.2 MAC. Each subject will have hemodynamic parameters measured at each dose of anaesthetic at each MAC. Five measurements of hemodynamic parameters will be recorded to minimize the effects of surgery on each measurement. The hemodynamic variables will be measured using a Flotrak and Vigeleo monitor and the quantities to be measured are: heart rate, blood pressure, systemic vascular resistance, systemic vascular resistance index, cardiac output, cardiac index, central venous pressure, stroke volume variation. The subjects are offered the opportunity to donate DNA for future study of hypertension.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension
Keywords
Hypertension, Sevoflurane, Inhaled Anesthetic, Angiotensin Converting Enzyme Inhibitor, Angiotensin II Receptor Blocking Agent

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Angiotensin Converting Enzyme Exposed
Arm Type
Other
Arm Description
Sevoflurane/oxygen/air/nitrous oxide Hypertensive patients exposed to Angiotensin Converting Enzyme Inhibitors (ACE Inhibitors)will make up this arm. Preoperative Exposure to any of the following Angiotensin Converting Enzyme Inhibitors Enalapril (Vasotec/Renitec) Ramipril (Altace/Prilace/Ramace/Ramiwin/Triatec/Tritace) Quinapril (Accupril) Perindopril (Coversyl/Aceon) Lisinopril (Listril/Lopril/Novatec/Prinivil/Zestril) Benazepril (Lotensin) Imidapril (Tanatril) Zofenopril (Zofecard) Trandolapril (Mavik/Odrik/Gopten) Fosinopril (Fositen/Monopril)
Arm Title
Angiotensin Receptor Blocker Exposed
Arm Type
Other
Arm Description
Sevoflurane/oxygen/air/nitrous oxide Hypertensive patients exposed to Angiotensin Receptor Blocking Agents (ARBs). Preoperative Exposure to any of the following Angiotensin II Receptor Blocking Agents Losartan(Cozaar) Candesartan (Atacand) Valsartan (Diovan) Irbesartan (Avapro) Telmisartan (Micardis) Eprosartan (Teveten) Olemisartan (Benicar) Azilsartan (Edarbi)
Arm Title
Non ACE/ARB Exposed
Arm Type
Other
Arm Description
Sevoflurane/oxygen/air/nitrous oxide Hypertensive patients not exposed to angiotensin converting enzyme inhibitors or Angiotensin receptor blocking agents will be put into this arm.
Intervention Type
Other
Intervention Name(s)
Sevoflurane/oxygen/air/nitrous oxide
Other Intervention Name(s)
Sevoflurane (Sevorane, Ultane, Sojourn), 1,1,1,3,3,3-hexafluoro-2-(fluoromethoxy)propane, fluoromethyl hexafluoroisopropyl ether, Nitrous oxide, oxgyen, air, nitrogen
Intervention Description
Patients in each arm will be randomized to receive either: 50 per cent oxygen, air, and sevoflurane or 50% nitrous oxide, oxygen and sevoflurane. They will then cross over to the other gas mixture. The depth of each the anesthetic will be varied from 0.8 MAC (minimum alveolar concentration) to 1.6 MAC in 0.2 MAC steps. Hemodyamic variables will be measured at each anesthetic concentration (average of five measurements). Time will be allowed for anesthetic agent equilibration. Paralysis and analgesia using rocuronium and fentanyl will be provided to ensure patients do not move at low (less than 1.0 MAC. It is estimated the time for the cross over experiment will be approximately six hours.
Primary Outcome Measure Information:
Title
Systemic Vascular Resistance Index (SVRI)
Description
A calculated hemodyamic parameter that assesses the resistance the heart faces to the forward flow of blood. Corrected for body surface area. SVRI = (cardiac output/blood pressure)/body surface area.
Time Frame
approximately every 5 minutes for 6 hours
Secondary Outcome Measure Information:
Title
Heart Rate
Description
number of heart beats per minute
Time Frame
approximately every 5 minutes for 6 hours
Title
Systolic Blood Pressure
Description
force of blood flow (measured in mmHg)
Time Frame
approximately every 5 minutes for 6 hours
Title
Diastolic Blood Pressure
Description
force of blood flow (measured in mmHg)
Time Frame
approximately every 5 minutes for 6 hours
Title
Central Venous Pressure
Description
force of blood flow returning to the heart (measured in mmHg)
Time Frame
approximately every 5 minutes for 6 hours
Title
Cardiac Output (CO)
Description
Calculated volume of blood flow in Litres per minute(measured in mmHg). Cardiac Output = mean arterial pressure/systemic vascular resistance.
Time Frame
approximately every 5 minutes for 6 hours
Title
Cardiac Index (CI)
Description
Calculated volume of blood flow in Litres per minute(measured in mmHg/m2), corrected for body surface area. Cardiac Output = (mean arterial pressure/systemic vascular resistance)/body surface area.
Time Frame
approximately every 5 minutes for 6 hours
Title
Stroke Volume Varriation
Description
Calculated variation in stroke volume between heart beats (blood pressure = stroke volume x rate x systemic vascular resisitance).measured in real time throughout experiment, and at each anesthetic concentration
Time Frame
approximately every 5 minutes for 6 hours
Title
Systemic Vascular Resistance
Description
A calculated parameter reflecting the resistance the heart faces to the forward flow of blood. Not corrected for body surface area. SVR = cardiac ouptut / blood pressure. Measured at each concentraion of inhaled anesthetic
Time Frame
approximately every 5 minutes for 6 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: age over 40 composite head and neck tumor resection treated hypertension hypertension medications taken on morning of surgery (except diuretics) Exclusion Criteria: patient refusal age less than 40 or over 80 years combined surgical procedures emergency surgery Left ventricular ejection fraction less than 50 per cent calculated creatinine clearance less than 60 mL per minute
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Craig J Railton, MD PhD FRCPC
Phone
519 685 8500
Ext
58525
Email
Craig.Railton@lhsc.on.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Craig J Railton, MD, PhD
Organizational Affiliation
Lawson Health Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
London Health Sciences Centre - Victoria Campus
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5W9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Craig J Railton, MD, PhD
Phone
519 685 8500
Ext
58525
Email
Craig.Railton@lhsc.on.ca
First Name & Middle Initial & Last Name & Degree
Craig J Railton, MD, PhD
First Name & Middle Initial & Last Name & Degree
Jonathan Fairbairn, BSc
First Name & Middle Initial & Last Name & Degree
George Nicoloau, MD
First Name & Middle Initial & Last Name & Degree
Robert Gros, PhD
First Name & Middle Initial & Last Name & Degree
Jason Franklin, MD
First Name & Middle Initial & Last Name & Degree
John Yoo, MD
First Name & Middle Initial & Last Name & Degree
Kevin Fung, MD
First Name & Middle Initial & Last Name & Degree
Anthony Nichols, MD
First Name & Middle Initial & Last Name & Degree
Danielle McNeil, MD

12. IPD Sharing Statement

Links:
URL
http://www.ncbi.nlm.nih.gov/pubmed/20524103
Description
Relevant Reference
URL
http://www.ncbi.nlm.nih.gov/pubmed?term=J%20Am%20Coll%20Cardiol%202009%3B%2054%3A1778-84
Description
Relevant Reference

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Is There an Adverse Drug Reaction Between Renin-Angiotensin System Blockade and Inhaled Anesthetics

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