NCT01715584

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
80

participants targeted

Target at P25-P50 for phase_4 hypertension

Timeline
Completed

Started Jul 2012

Longer than P75 for phase_4 hypertension

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2012

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

October 1, 2012

Completed
28 days until next milestone

First Posted

Study publicly available on registry

October 29, 2012

Completed
7.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2019

Completed
Last Updated

August 23, 2017

Status Verified

August 1, 2017

Enrollment Period

7.5 years

First QC Date

October 1, 2012

Last Update Submit

August 22, 2017

Conditions

Keywords

HypertensionSevofluraneInhaled AnestheticAngiotensin Converting Enzyme InhibitorAngiotensin II Receptor Blocking Agent

Outcome Measures

Primary Outcomes (1)

  • 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.

    approximately every 5 minutes for 6 hours

Secondary Outcomes (8)

  • Heart Rate

    approximately every 5 minutes for 6 hours

  • Systolic Blood Pressure

    approximately every 5 minutes for 6 hours

  • Diastolic Blood Pressure

    approximately every 5 minutes for 6 hours

  • Central Venous Pressure

    approximately every 5 minutes for 6 hours

  • Cardiac Output (CO)

    approximately every 5 minutes for 6 hours

  • +3 more secondary outcomes

Study Arms (3)

Angiotensin Converting Enzyme Exposed

OTHER

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)

Other: Sevoflurane/oxygen/air/nitrous oxide

Angiotensin Receptor Blocker Exposed

OTHER

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)

Other: Sevoflurane/oxygen/air/nitrous oxide

Non ACE/ARB Exposed

OTHER

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.

Other: Sevoflurane/oxygen/air/nitrous oxide

Interventions

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.

Also known as: Sevoflurane (Sevorane, Ultane, Sojourn), 1,1,1,3,3,3-hexafluoro-2-(fluoromethoxy)propane, fluoromethyl hexafluoroisopropyl ether, Nitrous oxide, oxgyen, air, nitrogen
Angiotensin Converting Enzyme ExposedAngiotensin Receptor Blocker ExposedNon ACE/ARB Exposed

Eligibility Criteria

Age40 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

London Health Sciences Centre - Victoria Campus

London, Ontario, N6A 5W9, Canada

RECRUITING

Related Links

MeSH Terms

Conditions

Hypertension

Interventions

SevofluraneNitrous OxideAirNitrogen

Condition Hierarchy (Ancestors)

Vascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

Methyl EthersEthersOrganic ChemicalsHydrocarbons, FluorinatedHydrocarbons, HalogenatedHydrocarbonsNitrogen OxidesGasesInorganic ChemicalsNitrogen CompoundsOxidesOxygen CompoundsAtmosphereEnvironmentEcological and Environmental PhenomenaBiological PhenomenaMeteorological ConceptsEnvironment and Public HealthElements

Study Officials

  • Craig J Railton, MD, PhD

    London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Craig J Railton, MD PhD FRCPC

CONTACT

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor

Study Record Dates

First Submitted

October 1, 2012

First Posted

October 29, 2012

Study Start

July 1, 2012

Primary Completion

December 31, 2019

Study Completion

December 31, 2019

Last Updated

August 23, 2017

Record last verified: 2017-08

Locations