E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Postoperative ventilatory control |
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E.1.1.1 | Medical condition in easily understood language |
Breathing in postoperative care |
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E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038680 |
E.1.2 | Term | Respiratory depression postoper |
E.1.2 | System Organ Class | 100000004855 |
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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 |
This trial is designed to assess the effect of reversal of neuromuscular blockade by sugammadex or neostigmine on ventilatory control in healthy volunteers. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Healthy male volunteers aged 18 and older with a body mass index < 30 kg/m2. |
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E.4 | Principal exclusion criteria |
Known or suspected neuromuscular disorders impairing neuromuscular function; allergies to muscle relaxants, anesthetics or narcotics; a (family) history of malignant hyperthermia or any other muscle disease; any medical, neurological or psychiatric illness (including a history of anxiety). |
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E.5 End points |
E.5.1 | Primary end point(s) |
We will apply hypoxic and hypercapnic challenges and measure ventilation on a breath-to-breath basis using the Dynamic End-tidal Forcing (DEF) technique. This technique allows the manipulation of inspired gas concentrations to steer the end-tidal concentrations of O2 and CO2 independent of the ventilatory response or the concentrations of O2 and CO2 in mixed venous blood. The technique allows a reliable assessment of carotid body function (in this case hypoxia) without the confounding effects of variations in end-tidal CO2. Additioanlly we will obtained the ventilatory response to hypercapnia at hyperoxic conditions. This allows assessment of the response activity of the central chemoreceptors in the brainstem. HYPOXIA: Hypoxic responses will be obtained (1) prior to administration of rocuronium; (2) During administration of rocuronium at a TOF of 0.6; (3) at 5 min intervals following the end of the administration of rocuronium and the administration of the reversal agent. Hypoxia will be induced by lowering the end-tidal PO2 in a step-wise fashion from 14.5 kPa (110 mmHg) to 7 kPa (53 mmHg) for 2 min. Thereafter the end-tidal concentration will be returned to normoxic values. The target arterial oxygen saturation of this challenge is 80 ± 2%. This method allows assessment of the hypoxic ventilatory sensitivity (HVR) as defined by: HVR = [Delta ventilation from normoxia to hypoxia]/[Delta saturation from normoxia to hypoxia]. (Dahan et al., Anesthesiologu 1996) HYPERCAPNIA: We will apply two 7 min steps in end-tidal PCO2 at the background of a hyperoxic gas mixture. At the end-of each step a ventilation and arterial oxygen saturation will be obtained. This allows assessment of the hypercapnic ventilatory response slope (S) which is calculated by linear regression of Ventilation to PCO2. (Dahan et al. PLoS Med 2007). Hyperoxic conditions are used to silence the carotid bodies. See for example of hypoxic and hypercapnic challenges Figure 2. Additionally we will measure the diaphragm EMG activity to get an indication of diaphragm contribution to the measured responses.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During administration of muscle blockade and during the first 90 min following reversal. |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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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When all subjects (n = 36) completed 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 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |