E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 goal of the investigator is to find the ED50 (effective dose) for sugammadex to antagonize a deep rocuronium-induced neuromuscular block, and thus find the lowest dose of sugammadex that is still safe for clinical use. |
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E.2.2 | Secondary objectives of the trial |
- Finding the ED50 with 10% precision in a later stage - Finding the dosage, and its corresponding time to act, needed to antagonize a deep rocuronium-induced neuromuscular block - Determing if there is a threshold for the dose of sugammadex to ensure that there will be no recurarisation when antagonizing a deep rocuronium-induced neuromuscular block within 1 hour - Creating a guideline for the clinical doses of sugammadex depending on every level of rocuronium-induced neuromuscular block - Adverse events in all participants
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients scheduled to undergo elective maxillofacial surgical procedures with an expected duration of general anaesthesia of more than one hour - 18–65 years - body mass index 18.5–25.0 kg/m² - ASA I–II - general anesthesia with naso- or orotracheal intubation requiring only deep neuromusculair block (NMB) for the intubation procedure. - Male-to-female allocation ratio 1:1 was respected at patient selection.
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E.4 | Principal exclusion criteria |
- suspected difficult airway - bronchial asthma - chronic obstructive pulmonary disease - neuromuscular disease - suspected malignant hyperthermia - significant hepatic or renal dysfunction - glaucoma - allergy to the drugs used in this trial, and taking medication known to influence the effect of NMBAs. - Patients who participated in another study in ≤1 month will not be included - pregnant or breastfeeding patients. The following medications are known to interact with NMB (neuromuscular blocker): - Tetracyclines, aminoglycosides, polymyxins, and clindamycin potentiate neuromuscular blockade through inhibition of acetylcholine (ACh) release or desensitization of postjunctional nAChRs to ACh - Patients receiving chronic treatment of anti-epileptic drugs are relatively resistant to nondepolarizing NMBAs due to accelerated clearance of these drugs - Patients who take lithium can have a prolonged response to both depolarizing and nondepolarizing NMBAs - In laboratory studies, sertraline and amitriptyline inhibit butyrylcholinesterase - Local anesthetics (LAs) may enhance the effects of both depolarizing and nondepolarizing NMBAs through pre- and post-synaptic interactions at the neuromuscular junction (NMJ) Data on the effects of lidocaine on neuromuscular block are conflicting. Whereas one study reported that epidural lidocaine potentiated vecuronium-induced neuromuscular block , several studies have reported no effect of intravenous (IV) lidocaine on the onset, duration, or recovery from rocuronium-induced neuromuscular block ,
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E.5 End points |
E.5.1 | Primary end point(s) |
- Finding the ED50 with 20% precision in the first stage |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
TOF (Train of four) - first phase: every 15 seconds between 3 minutes and 15 minutes after injection - second phase: every 5 minutes between 15 minutes and 60 minutes after injection PTC (post tetanic count) - every 3 minutes between 3 minutes and 60 minutes |
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E.5.2 | Secondary end point(s) |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
different doses of sugammadex |
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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 |