E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
male and female patients aged 12 to 17 years
with spontaneous or artificial ventilation and clinical need for prolonged (>24h) light to
moderate sedation. |
|
E.1.1.1 | Medical condition in easily understood language |
male and female patients aged 12 to 17 years
with spontaneous or artificial ventilation and clinical need for prolonged (>24h) light to
moderate sedation. |
|
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 |
Evaluation of efficacy of Dexdor for prolonged sedation in paediatric patients;
evaluation of safety and tolerability of Dexdor in paediatric population |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age from 12 to 17 years;
2. Clinical need for prolonged (>24h) light to moderate sedation (target RASS = 0 to -3)
in patients with spontaneous or artificial ventilation (initially intubated and ventilated
patients). The List of Indications for planned administration of the investigational
product is presented in Appendix 3
3. Negative urine pregnancy test (for female patients)
4. Written informed consent must be obtained according to local regulations before
starting any study procedures other than pre-screening.
|
|
E.4 | Principal exclusion criteria |
1. Acute severe intracranial or spinal neurological disorder due to vascular causes,
infection, intracranial expansion or injury; any other disorder where sedation
assessment is not reliable due to any neurological conditions;
2. Uncompensated acute circulatory failure (systolic blood pressure [SBP] < 90 mmHg)
and / or permanent use of vasopressors);
3. Severe hypotension (systolic BP/diastolic BP < 90/50 mmHg) or hypertension (systolic
BP/diastolic BP > 150/100 mmHg);
4. Severe bradycardia (heart rate [HR] < 50 bpm) or tachycardia (HR >140 bpm);
5. A/V-conduction block II-III;
6. Severe hepatic impairment (bilirubin > 101 μmol/l, ALT > 3 x ULN);
7. Loss of hearing or vision, or any other condition which would significantly interfere
with the collection of study data;
8. Use of centrally acting alfa-2 agonists or antagonists (notably clonidine) in the period
less than 5x halflife between drug discontinuation and the time of randomisation;
9. Patients who have or are expected to have treatment withdrawn or withheld due to poor
prognosis (e.g. life expectancy less than 72 hours);
10. Patients receiving sedatives for therapeutic indications (e.g. epilepsy);
11. Patients allergic to dexmedetomidine and rescue medications (e.g. midazolam,
fentanyl);
12. Hemodialysis and peritoneal dialysis;
13. Those requiring deep sedation or neuromuscular blocking agents;
14. Burn injuries and other injuries requiring regular anaesthesia or surgery;
15. History / family history of malignant hyperthermia;
16. Patients unlikely to be weaned from the ventilator during the study;
17. Patients with early-onset ventilator-associated pneumonia;
18. Any investigational drug within the preceding 30 days;
19. Any other reason which in the investigator’s opinion would make it detrimental for the
subject to participate in the study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of patients requiring additional analgesics& sedatives (with calculation of
cumulative dose per hour for each particular medication).
The time spent in target sedation range |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 hour after start of study
treatment, and in every 4 hours during the treatment period with Dexdor infusion, in 1 hour
after discontinuation, and in every 4 hours during the first 24 hours of the post-treatment
period. |
|
E.5.2 | Secondary end point(s) |
Secondary endpoints:
Wake-up / discontinuation of sedation (if applicable);
Extubation assessment (if applicable). Time to extubation.
Time to first rescue medication. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 hour after start of study
treatment, and in every 4 hours during the treatment period with Dexdor infusion, in 1 hour
after discontinuation, and in every 4 hours during the first 24 hours of the post-treatment
period |
|
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 | 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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
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.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |