E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Brain damage after cardiac arrest |
Hersenschade na een hartstilstand |
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E.1.1.1 | Medical condition in easily understood language |
Brain damage |
Hersenschade |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
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 |
We aim to estimate safety and efficacy of intravenous treatment with acyl-ghrelin to promote cerebral recovery in comatose patients after cardiac arrest. Safety will be monitored throughout hospitalization and during follow-up using all AEs reported, and by interim analyses by an independent DSMB. Efficacy will be measured by the primary outcome measure, i.e. functional recovery as measured by the Cerebral Performance Category (CPC) scale at six months after cardiac arrest. |
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E.2.2 | Secondary objectives of the trial |
To estimate efficacy of ghrelin to modify
1. Case fatality
2. Time to awaken (time interval between resuscitation and Glasgow Coma Scale (GCS) score of 14)
3. Long term outcome: CPC and cognitive functioning at 12 months
4. Cardiovascular outcomes, including blood pressure, treatment with inotropic medication, treatment with vasopression, LVAD, cardiac biomarkers, and need for defibrillation
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age ≥18 years
• Out of hospital cardiac arrest
• Successful cardiopulmonary resuscitation
• Return of spontaneous circulation ≤12 hours ago
• GCS score on admission ≤ 8 or suspected coma in patients who are sedated
• Admission to intensive care unit
• Hemodynamic and respiratory stability as determined by the treating intensive care physician, with the minimum requirement of mean arterial pressure > 65 mmHg. Treatment with inotropes, vasopressors or IABP is allowed.
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E.4 | Principal exclusion criteria |
• Age <18 years
• A known progressive neurological disease
• Expected death within 48 hours |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure will be functional outcome as expressed as the score on the cerebral performance category (CPC) at 6 months. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary outcomes include case fatality at one week and 6 months, time to awaken (time interval between resuscitation and GCS score of 14), EMV score and estimated CPC score at 1 week, CPC score at 3 and 12 months, and cognitive functioning at 12 months.
Cardiovascular secondary outcome measures are:
Mean arterial blood pressure day 1-7 (mean, highest, lowest)
Heart rate day 1-7 (mean, highest, lowest)
Arrhythmia day 1-7: yes / no. If yes: type of arrhythmia
Cumulative dose of vasopressive medication day 1-7
Cumulative dose of inotropic medication day 1-7
Sequential Organ Failure Assessment score day 1-7
Kidney function day expressed as GFR day 1-7
CVVH day 1-7: yes / no
Assist devices day 1-7: yes / no
Biomarkers are:
Cardiac: troponine and CK / CK-MB ratio at day 0, 1, 2 or 3
Neurological: NSE day 1, 2, 3
Endocrinological: cortisol, growth hormone, prolactine, ACTH, IGF-1 day 1, 2, 3
Gastro-intestinal outcome measure is: gastric residual volume (day 1-7, during ICU admission) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Daily after administering medication/placebo for a week; 1 week, 3 months, 12 months |
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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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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) | 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 | 4 |
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 | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |