Hemodynamic InstabilityWalibiNCT02067936
Walking the Isobole of Drug Interaction
A study testing Group A propofol + remifentanil, Group B propofol + remifentanil and Group C propofol + remifentanil in people with Hemodynamic Instability and Disorder of Oxygen Transport, run by University Medical Center Groningen at 1 site in Netherlands.
Trial summary
The investigators study whether four equipotent combinations of propofol and remifentanil (as predicted by interaction models for "tolerance of laryngoscopy") result in identical haemodynamic conditions, independent of their relative different balance between the concentration of propofol and remifentanil. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hemodynamic Instability, Disorder of Oxygen Transport, Interaction
- What is being tested?
- Group A propofol + remifentanil, Group B propofol + remifentanil and Group C propofol + remifentanil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- 1 siteNetherlands
- Study dates
- Feb 2014to Sep 2015
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent
- General anesthesia required for the procedure
- Age: 18 years and older
- American Society of Anesthesiologists (ASA) physical status I to III
Who cannot join
- Refusal to participate in this study
- Contra-indications for the use of propofol or remifentanil
- BMI > 35 kg/m2
- Central nervous system disorders (i.e. cerebrovascular accident, dementia, seizures, psychiatric disorders)
- Relevant hepatic disease (Child B or higher)
- Regular use of medication that affects the central nervous system (i.e. benzodiazepines, antidepressants, antipsychotics, antiepileptic drugs)
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- Use of alpha-agonists or beta-blockers
- Overt signs of alcohol abuse
- Use of preoperative benzodiazepines (on the day of the study)
- Beta blockers eye drips
- Overt signs of Drugs abuse
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
University Medical Center Groningen
Groningen, Provincie Groningen, 9713EZ
About this study
Official title: Walking the Isobole of Drug Interaction: Comparison of Hemodynamic Effects, Cerebral and Tissue Oxygenation for 4 Equipotent Combinations of Propofol and Remifentanil
The investigators study whether four equipotent combinations of propofol and remifentanil (as predicted by interaction models for "tolerance of laryngoscopy") result in identical haemodynamic conditions, independent of their relative different balance between the concentration of propofol and remifentanil.
Read the detailed description
In anesthesia, the synergistic interaction between hypnotics and opioids is applied daily to give adequate anesthesia and analgesia at significantly lower doses compared with the ones needed if only one drug was given to reach the same effect. A lot of research has been done to quantify these interactions with a focus on the desired effects (Tolerance of laryngoscopy, tolerance of shake and shout etc...), but the simultaneous interaction on the unwanted side effects is less well described. The response surface model of Bouillon et al. and other models predict combinations of propofol and remifentanil effect-site concentrations that lead to an equipotent desired effect. Due to the availability of the models, the anesthesiologists now could use the knowledge on interactions to target specific effects more accurately, using predefined equipotent combinations of drugs: for instance, a desirable 90% probability of tolerance of laryngoscopy (TOL90) in the population can be reached through either a high propofol/low remifentanil combination, but equally well through a low propofol-high remifentanil combination.
However, at this time it is not known whether some of the combinations of propofol and remifentanil have a favorable hemodynamic stability compared to other equipotent combinations. The researcher in this study want to determine whether equipotent combinations of remifentanil and propofol (all deliberately selected to evoke 90% probability of "tolerance to laryngoscopy"), result in different effects on the undesired side effects of anesthetics, such as hemodynamic instability (hypotension, changes in heart rate or cardiac output), decreases in cerebral or tissue oxygenation (both measured with near infrared spectroscopy).
- Being tested
- Group A propofol + remifentanil, Group B propofol + remifentanil, Group C propofol + remifentanil, group D propofol + remifentanil
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Group A propofol + remifentanilDrug
Also called propofol highest dose + remifentanil lowest dose
Predicted TOL90% according to Bouillon model
Group B propofol + remifentanilDrug
Also called Propofol intermediate high+ remifentanil intermediate low
TOL 90% according to the Bouillon interaction model
Group C propofol + remifentanilDrug
Also called propofol intermediate low+remifentanil intermediate high
TOL 90% according to the Bouillon interaction model
group D propofol + remifentanilDrug
Also called Propofol lowest dose+ remifentanil highest
TOL 90% according to the Bouillon interaction model
| Study group | Role | What they receive |
|---|---|---|
| Group A propofol + remifentanil | Active comparator | Propofol highest dose, remifentanil lowest dose, TOL 90% according to Bouillon model Receives: Drug: Group A propofol + remifentanil |
| Group B propofol + remifentanil | Active comparator | Propofol intermediate high, remifentanil intermediate low, TOL90% according to the Bouillon Model Receives: Drug: Group B propofol + remifentanil |
| Group C propofol + remifentanil | Active comparator | propofol intermediate low+ remifentanil intermediate high: TOL 90% according to the Bouillon interaction model Receives: Drug: Group C propofol + remifentanil |
| group D propofol + remifentanil | Active comparator | propofol lowest dose+ remifentanil highest dose: TOL 90% according to the Bouillon model Receives: Drug: group D propofol + remifentanil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood pressure
Continuously stored on a laptop (systolic, diastolic and mean blood pressure over time) using a Philips Non Invasive Blood Pressure measurements every minute and a Nexfin monitor (continuous non invasive blood pressure measurement)
Measured: From start drug till intubation which will take on average 15 minutes of measurement
Secondary outcomes (5)
Electro Encephalographic derived indices of anesthetic depth
Bispectral index, Wavelet Transformation (WAV) index, Quantium Consciousness Index (qCON), Quantium Nociception Index (qNOX) to observe whether multiple electroencephalographic derived depth of anesthesia indices indicate the same equipotent effect in all 4 groups. All these measures are unitless values that range between 100 (for a fully responsive condition) and 0 (for a fully unresponsive condition). All these measures are extracted from the same frontal electroencephalogram but use different composite mathematical algorithms to translate the cortical state in numbers. We want to observe whether these composite algorithms measure consistent behavior between groups. This outcome is mainly ment as hypothesis generating for future research.
Measured: From start first drug till intubation, which will take on average 15 minutes of measurement
Cerebral and tissue oxygenation
Continuously stored oxygenation saturation measured in tissue and cerebral cortex as measured by Near Infrared Spectrum Analysis (Forsyth monitor) and Inspectra monitor. Comparing differences between 4 groups with ANOVA.
Measured: From start drug till intubation, which will take on average 15 minutes of measurement
Heart rate
Difference in median/mean heart rate to determine differences between 4 groups with ANOVA.
Measured: From start first drug till intubation, which will take on average 15 minutes of measurement
Probability of tolerance to laryngoscopy
During pharmacological steady state of propofol/remifentanil, a laryngoscopy will be performed by one researcher and response or tolerance of the stimulus will be observed. A positive response will be defined as any somatic movement, swallowing or coughing during three minutes after laryngoscopy was applied. Also a increase in heart rate or systolic blood pressure of more than 20% from baseline values (one minute before laryngoscopy) will be defined as a positive response. Through PROBIT analysis we can plot the probability of response to laryngoscopy (%) as a function of respectively propofol or remifentanil drug concentrations.
Measured: one minute before laryngoscopy till three minutes after
Cardiac index
Non invasive estimation of Cardiac output and Cardiac index patterns through the Nexfin monitor. Determine the differences between groups through ANOVA.
Measured: From start first drug till intubation, which will take on average 15 minutes of measurement
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2014 (estimated)
- Study startFeb 2014
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemodynamic InstabilityStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe 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 N/A
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hugo E.M.Vereecke, University Medical Center Groningen
- Investigators
- Hugo EM Vereecke, MD, PhD, Principal investigator, University Hospital Medical center, university of groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02067936
- Sponsor's protocol ID
- WALIBI-001
- Acronym
- Walibi
- Status last verified
- Dec 2015
- First submitted
- 3 Feb 2014
- Last updated
- 4 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Walking the Isobole of Drug Interaction: Comparison of Hemodynamic Effects, Cerebral and Tissue Oxygenation for 4 Equipotent Combinations of Propofol and Remifentanil
- ClinicalTrials.gov ID
- NCT02067936
- Acronym / sponsor ID
- Walibi / WALIBI-001
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 87 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Study start
- Feb 2014
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 20 Feb 2014 (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.
The investigators study whether four equipotent combinations of propofol and remifentanil (as predicted by interaction models for "tolerance of laryngoscopy") result in identical haemodynamic conditions, independent of their relative different balance between the concentration of propofol and remifentanil.
Detailed description
In anesthesia, the synergistic interaction between hypnotics and opioids is applied daily to give adequate anesthesia and analgesia at significantly lower doses compared with the ones needed if only one drug was given to reach the same effect. A lot of research has been done to quantify these interactions with a focus on the desired effects (Tolerance of laryngoscopy, tolerance of shake and shout etc...), but the simultaneous interaction on the unwanted side effects is less well described. The response surface model of Bouillon et al. and other models predict combinations of propofol and remifentanil effect-site concentrations that lead to an equipotent desired effect. Due to the availability of the models, the anesthesiologists now could use the knowledge on interactions to target specific effects more accurately, using predefined equipotent combinations of drugs: for instance, a desirable 90% probability of tolerance of laryngoscopy (TOL90) in the population can be reached through either a high propofol/low remifentanil combination, but equally well through a low propofol-high remifentanil combination.
However, at this time it is not known whether some of the combinations of propofol and remifentanil have a favorable hemodynamic stability compared to other equipotent combinations. The researcher in this study want to determine whether equipotent combinations of remifentanil and propofol (all deliberately selected to evoke 90% probability of "tolerance to laryngoscopy"), result in different effects on the undesired side effects of anesthetics, such as hemodynamic instability (hypotension, changes in heart rate or cardiac output), decreases in cerebral or tissue oxygenation (both measured with near infrared spectroscopy).
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group A propofol + remifentanil | Active comparator | Drug: Group A propofol + remifentanilPropofol highest dose, remifentanil lowest dose, TOL 90% according to Bouillon model |
| Group B propofol + remifentanil | Active comparator | Drug: Group B propofol + remifentanilPropofol intermediate high, remifentanil intermediate low, TOL90% according to the Bouillon Model |
| Group C propofol + remifentanil | Active comparator | Drug: Group C propofol + remifentanilpropofol intermediate low+ remifentanil intermediate high: TOL 90% according to the Bouillon interaction model |
| group D propofol + remifentanil | Active comparator | Drug: group D propofol + remifentanilpropofol lowest dose+ remifentanil highest dose: TOL 90% according to the Bouillon model |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Written informed consent
- General anesthesia required for the procedure
- Age: 18 years and older
- American Society of Anesthesiologists (ASA) physical status I to III
Key exclusion criteria (11 listed)
- Refusal to participate in this study
- Contra-indications for the use of propofol or remifentanil
- BMI > 35 kg/m2
- Central nervous system disorders (i.e. cerebrovascular accident, dementia, seizures, psychiatric disorders)
- Relevant hepatic disease (Child B or higher)
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 |
|---|---|---|
| Group A propofol + remifentanilAlso: propofol highest dose + remifentanil lowest dosePredicted TOL90% according to Bouillon model | Drug | Group A propofol + remifentanil |
| Group B propofol + remifentanilAlso: Propofol intermediate high+ remifentanil intermediate lowTOL 90% according to the Bouillon interaction model | Drug | Group B propofol + remifentanil |
| Group C propofol + remifentanilAlso: propofol intermediate low+remifentanil intermediate highTOL 90% according to the Bouillon interaction model | Drug | Group C propofol + remifentanil |
| group D propofol + remifentanilAlso: Propofol lowest dose+ remifentanil highestTOL 90% according to the Bouillon interaction model | Drug | group D propofol + remifentanil |
Primary outcome
Blood pressure
Time frame: From start drug till intubation which will take on average 15 minutes of measurement
Continuously stored on a laptop (systolic, diastolic and mean blood pressure over time) using a Philips Non Invasive Blood Pressure measurements every minute and a Nexfin monitor (continuous non invasive blood pressure measurement)
5 secondary outcomes
Electro Encephalographic derived indices of anesthetic depth
Time frame: From start first drug till intubation, which will take on average 15 minutes of measurement
Cerebral and tissue oxygenation
Time frame: From start drug till intubation, which will take on average 15 minutes of measurement
Heart rate
Time frame: From start first drug till intubation, which will take on average 15 minutes of measurement
Probability of tolerance to laryngoscopy
Time frame: one minute before laryngoscopy till three minutes after
Cardiac index
Time frame: From start first drug till intubation, which will take on average 15 minutes of measurement
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2015.
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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.
Hugo EM Vereecke, MD, PhD principal investigator
University Hospital Medical center, university of groningen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Group A propofol + remifentanil, Group B propofol + remifentanil and Group C propofol + remifentanil in people with Hemodynamic Instability and Disorder of Oxygen Transport, run by University Medical Center Groningen at 1 site in Netherlands.
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 11 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: finished, as of the sponsor's last update on 4 Dec 2015. 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 Netherlands. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood pressure (time frame: From start drug till intubation which will take on average 15 minutes of measurement). 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 4 Dec 2015.