E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
elective ophthalmic surgery under general anesthesia. |
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E.1.1.1 | Medical condition in easily understood language |
elective ophthalmic surgery under general anesthesia. |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the effects of the different combinations of propofol and remifentanil on the isobole of TOL90 and to compare hemodynamics, cerebral and tissue oxygenation for each equipotent combination. To describe the combination of propofol and remifentanil on the TOL90 isobole with the least hemodynamic side effects. This study will help the anesthesiologist to increase the safety of induction and maintenance of anesthesia as we will be able to provide a priori information on those combinations with the least side effects. Currently, the post hoc (after the induction) monitoring of side effects is the only way to guarantee safet |
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E.2.2 | Secondary objectives of the trial |
To investigate the effects of the different combinations of propofol and remifentanil on the isobole of TOL90 and to compare hemodynamics, cerebral and tissue oxygenation for each equipotent combination. To describe the combination of propofol and remifentanil on the TOL90 isobole with the least hemodynamic side effects. This study will help the anesthesiologist to increase the safety of induction and maintenance of anesthesia as we will be able to provide a priori information on those combinations with the least side effects. Currently, the post hoc (after the induction) monitoring of side effects is the only way to guarantee safet |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- General anesthesia required for the procedure
- Age: 18 years and older
- American Society of Anesthesiologists (ASA) physical status I to III
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E.4 | Principal exclusion criteria |
- 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)
- Use of alpha-agonists or beta-blockers
- Overt signs of alcohol abuse
- Use of preoperative benzodiazepines (on the day of the study)
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E.5 End points |
E.5.1 | Primary end point(s) |
1) During non-steady-state induction: The relationship between changing drug concentrations of remifentanil and propofol with the changing BIS, Neurowave index, heart rate, non-invasive arterial blood pressure, cardiac output, StO2 and SctO2.
2) During maintenance (after equilibration at steady state TOL90), absolute bispectral index, Neurowave index, heart rate, non-invasive arterial blood pressure, cardiac output, StO2 and SctO2, and changes from baseline for all |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Total dose of atropine and ephedrine required to maintain heart rate > 40/min and mean arterial blood pressure > 60 mmHg, respectively.
Tolerance of laryngoscopy at steady state TOL90: observing the number of responders to laryngoscopy at TOL90. Response is defined as significant motor response (movement of extremities, opening of eyes, gag reflex or coughing) or hemodynamic response (= 20% difference between the median HR, blood pressure or cardiac output of one minute before laryngoscopy, compared to the median values one minute after laryngoscopy). The probability of memory formation of these events is extremely low (even in the responders) due to the TOL90 dosing level that is far above the 99% tolerance of shake and shout level.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |