HypertensionPhase 4NCT01715584
Is There an Adverse Drug Reaction Between Renin-Angiotensin System Blockade and Inhaled Anesthetics
A Phase 4 study testing Sevoflurane/oxygen/air/nitrous oxide in people with Hypertension, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Hypertension
- What is being tested?
- Sevoflurane/oxygen/air/nitrous oxide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2012to 31 Dec 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age over 40
- composite head and neck tumor resection
- treated hypertension
- hypertension medications taken on morning of surgery (except diuretics)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
London Health Sciences Centre - Victoria Campus
London, Ontario, N6A 5W9
Craig J Railton, MD, PhD, 519 685 8500 ext. 58525, Craig.Railton@lhsc.on.ca
Craig J Railton, MD, PhD
About this study
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.
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.
Read the 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.
- Conditions
- Hypertension
- Being tested
- Sevoflurane/oxygen/air/nitrous oxide
- Keywords
- Hypertension, Sevoflurane, Inhaled Anesthetic, Angiotensin Converting Enzyme Inhibitor, Angiotensin II Receptor Blocking Agent
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sevoflurane/oxygen/air/nitrous oxideOther
Also called Sevoflurane (Sevorane, Ultane, Sojourn), 1,1,1,3,3,3-hexafluoro-2-(fluoromethoxy)propane, fluoromethyl hexafluoroisopropyl ether, Nitrous oxide
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.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: 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. Receives: Other: Sevoflurane/oxygen/air/nitrous oxide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: approximately every 5 minutes for 6 hours
Secondary outcomes (8)
Heart Rate
number of heart beats per minute
Measured: approximately every 5 minutes for 6 hours
Systolic Blood Pressure
force of blood flow (measured in mmHg)
Measured: approximately every 5 minutes for 6 hours
Diastolic Blood Pressure
force of blood flow (measured in mmHg)
Measured: approximately every 5 minutes for 6 hours
Central Venous Pressure
force of blood flow returning to the heart (measured in mmHg)
Measured: approximately every 5 minutes for 6 hours
Cardiac Output (CO)
Calculated volume of blood flow in Litres per minute(measured in mmHg). Cardiac Output = mean arterial pressure/systemic vascular resistance.
Measured: approximately every 5 minutes for 6 hours
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.
Measured: approximately every 5 minutes for 6 hours
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
Measured: approximately every 5 minutes for 6 hours
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
Measured: approximately every 5 minutes for 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2012 (estimated)
- Study startJul 2012
- Primary completion31 Dec 2019 (estimated)
- Study completion31 Dec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Collaborators
- University of Western Ontario, Canada
- Responsible party
- Principal investigator, Craig Railton, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Investigators
- Craig J Railton, MD, PhD, Principal investigator, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01715584
- Sponsor's protocol ID
- 5982
- Status last verified
- Aug 2017
- First submitted
- 1 Oct 2012
- Last updated
- 23 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01715584
- Acronym / sponsor ID
- 5982
- Conditions
- Hypertension
- Keywords
- Hypertension, Sevoflurane, Inhaled Anesthetic, Angiotensin Converting Enzyme Inhibitor, Angiotensin II Receptor Blocking Agent
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Collaborators
- University of Western Ontario, Canada
- Study start
- Jul 2012
- Primary completion
- 31 Dec 2019 (estimated)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 29 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Angiotensin Converting Enzyme Exposed | Other | Other: Sevoflurane/oxygen/air/nitrous oxideSevoflurane/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) |
| Angiotensin Receptor Blocker Exposed | Other | Other: Sevoflurane/oxygen/air/nitrous oxideSevoflurane/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) |
| Non ACE/ARB Exposed | Other | Other: Sevoflurane/oxygen/air/nitrous oxideSevoflurane/oxygen/air/nitrous oxide Hypertensive patients not exposed to angiotensin converting enzyme inhibitors or Angiotensin receptor blocking agents will be put into this arm. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- age over 40
- composite head and neck tumor resection
- treated hypertension
- hypertension medications taken on morning of surgery (except diuretics)
Key exclusion criteria (6 listed)
- patient refusal
- age less than 40 or over 80 years
- combined surgical procedures
- emergency surgery
- Left ventricular ejection fraction less than 50 per cent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sevoflurane/oxygen/air/nitrous oxideAlso: Sevoflurane (Sevorane, Ultane, Sojourn), 1,1,1,3,3,3-hexafluoro-2-(fluoromethoxy)propane, fluoromethyl hexafluoroisopropyl ether, Nitrous oxidePatients 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. | Other | Angiotensin Converting Enzyme Exposed, Angiotensin Receptor Blocker Exposed, Non ACE/ARB Exposed |
Primary outcome
Systemic Vascular Resistance Index (SVRI)
Time frame: approximately every 5 minutes for 6 hours
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.
8 secondary outcomes
Heart Rate
Time frame: approximately every 5 minutes for 6 hours
Systolic Blood Pressure
Time frame: approximately every 5 minutes for 6 hours
Diastolic Blood Pressure
Time frame: approximately every 5 minutes for 6 hours
Central Venous Pressure
Time frame: approximately every 5 minutes for 6 hours
Cardiac Output (CO)
Time frame: approximately every 5 minutes for 6 hours
Cardiac Index (CI)
Time frame: approximately every 5 minutes for 6 hours
Stroke Volume Varriation
Time frame: approximately every 5 minutes for 6 hours
Systemic Vascular Resistance
Time frame: approximately every 5 minutes for 6 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2017.
- Relevant ReferenceLink provided by the sponsor.
- Relevant ReferenceLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Craig J Railton, MD, PhD principal investigator
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sevoflurane/oxygen/air/nitrous oxide in people with Hypertension, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Craig J Railton, MD PhD FRCPC (519 685 8500 ext. 58525, Craig.Railton@lhsc.on.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Systemic Vascular Resistance Index (SVRI) (time frame: approximately every 5 minutes for 6 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2017.