E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Some patients develop high respiratory drive during partially supported mechanical ventilation which is associated with lung and diaphragm injury and worse clinical outcome |
|
E.1.1.1 | Medical condition in easily understood language |
Injury to lung and/or diaphragm due to mechanical ventilation |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
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 goal is to investigate the feasibility and safety of prolonged (24 hours) partial neuromuscular blockade in ventilated patients with high respiratory drive in partially supported mode. |
|
E.2.2 | Secondary objectives of the trial |
The secondary goal is to evaluate the effect of this strategy on
diaphragm function, lung injury, hemodynamics and systemic
inflammation compared to standard care. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients are eligible for inclusion if they meet all of the following
criteria:
- high respiratory drive, defined as tidal volume > 8ml/kg PBW on
inspiratory support of 12cmH2O.
- sedation level: RASS ≤ -3
- ventilated in pressure support mode |
|
E.4 | Principal exclusion criteria |
A potential subject who meets any of the following criteria will be
excluded from participation in this study:
- recent use of NMBA (< 2 hrs)
- arterial pH < 7.25
- hemodynamic instability, i.e. high dose vasopressors (>0.5 μg/kg/min)
or inotropes (dobutamine >15 μg/kg/min or enoximone >25
μg/kg/min)
- intracranial pressure > 20 cmH2O
- past medical history of neuromuscular disorders
- pregnancy
- known previous anaphylactic reaction to NMBA's. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Feasibility to establish and maintain lung protective ventilation for 24
hours with partial neuromuscular blockade in ventilated ICU patients
with high respiratory drive in partially supported mode. 'Feasible' is
define as: 'the ability to maintain tidal volume <6ml/kg PBW during the
whole study protocol, without developing any directly related serious
adverse events.'
Therefore, the following parameters are collected:
Feasibility
• Percentage of breaths with tidal volume < 6ml/kg PBW
• Number of patients completing the study without meeting the stopping
criteria (see section 7.4.2) or serious adverse events.
• Number of patients that have been withdrawn after inclusion, and
reason for withdrawal.
• Number of eligible patients of the total ICU population, and reason why
the patient is not eligible for inclusion.
• Time needed to recruit patients and collect data.
Safety:
• Number of directly related adverse events
• Blood gas analysis: pCO2 and pH
• Hemodynamic parameters: heart rate and blood pressure
• Days on mechanical ventilation after the intervention
• ICU mortality |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
During the study period, after 24hr and 48hr |
|
E.5.2 | Secondary end point(s) |
The effect of prolonged partial neuromuscular blocking on diaphragm
function and respiratory, hemodynamic and inflammatory parameters
compared to standard care. Therefore, the following parameters are
collected:
• Respiratory and diaphragm function, assessed by measuring:
- respiratory rate, tidal volume and SpO2
- work of breathing (WOB) and pressure-time product (PTP)
- blood gas analysis: PaO2, PaCO2, pH
• Hemodynamic parameters, such as blood pressure and heart rate.
• Inflammatory parameters in blood; including TNF-α, IL-6 and IL-1β |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
During the study period, after 24hr and 48hr |
|
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 | Yes |
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 | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 15 |
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
|
|
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 | |
E.8.9.1 | In the Member State concerned days | |