E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Intraoperative analgesia during general anesthesia |
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E.1.1.1 | Medical condition in easily understood language |
The unconscious response of patients to painful stimulus during 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 |
The primary outcome is quantity of administered remifentanil |
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E.2.2 | Secondary objectives of the trial |
Secondary outcomes will include postoperative opioid administration, opioid associated complications, hemodynamics, and hospital length of stay. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
There may be a substudy of long term impact |
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E.3 | Principal inclusion criteria |
Included patients will be American Society of Anesthesiologists (ASA) grades 1-2 undergoing scheduled maxilloafacial, plastic, ear-nose-throat, thyroid, or cervicofacial surgery anticipated to last at least two hours. A total of 50 patients per group will be included. |
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E.4 | Principal exclusion criteria |
ASA score >2, use of regional anesthesia, preoperative organ dysfunction, patients with non-regular cardiac rhythm, implanted pacemakers, emergent surgery, pregnancy or lactation, allergy or intolerance to any of the study drugs, and patient’s refusal. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome is intraoperative consumption of remifentanil to maintain NOL-Index between 10 and 25.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Intraoperative period (less than 24h) |
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E.5.2 | Secondary end point(s) |
Intraoperative outcomes will include: estimated blood loss, use and amount of vasoactive drugs used (ephedrine/phenylephrine/noradrenaline), use and amount of hypotensive drugs used (nicardipine/esmolol), quantity of propofol, quantity of fluids, time to extubation of patient, hypotension and duration (defined as MAP<65 mmHg*), hypertension and duration ( defined as MAP≥100), hemodynamic instability (MAP<65 mmHg*, HR<45, MAP≥100, HR>90) for a period at least 3 minutes, blood pressure, HR, and NOL-Index measurement during key intraoperative periods (before induction, after induction, after intubation, before incision, after incision, every 15 minutes after incision, after end of surgery, and after reversal of anesthesia). Post-operative variables include postoperative opioid consumption, occurrence of postoperative opioid-related side effect (PONV within the first 24 h, postoperative hypoxemia (need within 24h postop to have supplemental oxygen (to maintain sat >94%), postoperative hypopnea (defined as less than 8 rpm), postoperative ileus (absence of flatus or stools throughout the first 48 postoperative hours), postoperative cognitive dysfunction using CAM-ICU (i.e. acute onset or fluctuating course + inattention and either disorganized thinking or altered level of consciousness), pruritus, postoperative hyperalgesia (addressed using calibrated von Frey hairs), time to fit for PACU discharge, postoperative Ramsay sedation score (at arrival then every 30 minutes PACU), PACU length of stay (LOS), fit for discharge PACU LOS based on Aldrete Score, postoperative complications, hospital LOS, and fit for discharge hospital LOS (patient is fully oriented and able to move without nursing support, hemodynamically stable, laboratory parameters with no sign of increasing organ dysfunction or infection, and no clinical signs of active wound infection). * Patients that have chronic hypertension or that are 65 years of age or older will have a MAP threshold of 75mmHg (and not 65mmHg). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Intraoperative endpoints: less than 24h Postoperative endpoints: from end of surgery to end of hospital stay |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
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 | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
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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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 | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |