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 | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007517 |
E.1.2 | Term | Cardiac arrest transient |
E.1.2 | System Organ Class | 100000004849 |
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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 |
Evaluating the safety and efficacy of low-dose Iloprost administration and blood pressure in
addition to standard therapy, as compared to standard therapy alone, in
post-cardiac-arrest-syndrome patients. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Low-dose Prostacyclin effect on Hemostasis in patients suffering from
Post Cardiac Arrest Syndrome
Version 1
01-04-2014
Objective:
Evaluate the effect of low-dose prostacyclin infusion on hemostasis and
microparticle- formation in PCAS patients as compared to PACS patients
not receiving prostacyclin, evaluated by TEG ®, Multiplate® and Flowcytometry |
|
E.3 | Principal inclusion criteria |
1. Age ≥18 years
2. OHCA of presumed cardiac cause
3. Sustained ROSC*
4. Unconsciousness (GCS <8) (patients not able to obey verbal
commands) after sustained ROSC
5. Target temperature management is indicated. |
|
E.4 | Principal exclusion criteria |
1. Conscious patients (obeying verbal commands)
2. Females of childbearing potential (unless a negative HCG test can rule
out pregnancy within the inclusion window)
3. In-hospital cardiac arrest (IHCA)
4. OHCA of presumed non-cardiac cause, e.g. after trauma or
dissection/rupture of major artery OR Cardiac arrest caused by initial
hypoxia (i.e. drowning, suffocation, hanging).
5. Known congenital bleeding diathesis (medically induced coagulopathy
due to treatment with Vitamin K antagonists, Thrombininhibitors, Factor
Xa inihbitors, ADP-receptor inhibitors, Aspirin, Asasantin, Persantin,
NSAID, unfractionated and low molecular weight heparin does NOT
exclude the patient).
6. Suspected or confirmed acute intracranial bleeding
7. Suspected or confirmed acute stroke
8. Unwitnessed asystole
9. Known limitations in therapy and Do Not Resuscitate-order
10. Known disease making 180 days survival unlikely
11. Known pre-arrest CPC 3 or 4
12. >4 hours (240 minutes) from ROSC to screening
13. Systolic blood pressure <80 mm Hg in spite of fluid
loading/vasopressor and/or inotropic medication/intra aortic balloon
pump/axial flow device*
14. Temperature on admission <30°C.
15. Known allergy to Prostacyclin analogues |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change in biomarkers indicative of endothelial activation and damage
(sE-selectin, syndecan-1, thrombomodulin, sVE-cadherin, nucleosomes)
and sympathoadrenal overactivation (Epinephrine/norepinephrine) from
baseline to 48 hours post-randomization. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
48 hours post-randomization |
|
E.5.2 | Secondary end point(s) |
Secondary endpoints: Change in functional hemostatic blood test
(Thromboelastography (TEG) and whole blood platelet aggregometry
(Multiplate)) and blood cell and endothelial cell derived microparticles
from baseline to 48 hours post-randomization. Feasibility of blood pressure target intervention (target 90%). Interaction of primary end-points and blood pressure target. Blood pressure target impact on levels of NSE at 48h and 72 h post inclusion
Tertiary endpoints: (1) Days of vasopressor, ventilator and renal
replacement therapy post-randomization. (2) Changes in SOFA score
from baseline to 48 h and day 5 and 7 post-randomization. (3)
Neurological function graded by modified Rankong Scale (mRS) and
Cerebral Performance Category (CPC) at 180 days. (4) Severe bleeding
(intracranial or clinical bleeding with the use of 3 RBC units or more/24
hours). (5) Use of blood products (in ICU) post-randomization. (6)
Difference in day 7, 30 and 180 day mortality between patients receiving
active treatment (lloprost) and placebo. EGFR and urine output on day 2 and 3, need for renal replacement therapy during the ICU stay. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoint: 48 hours post-randomization
Tertiary endpoints: evaluated througout the 48 hour treatment period
and after 7, 30, 90 and 180 days |
|
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 | 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 | 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
|
All patients who withdraw from the trial for any reason and at any time
should have an end of trial examination. Patients will be examined for
any status changes that require further follow-up. All withdrawn
patients will be followed-up as the remaining patients in the trial. If
consent is withdrawn, the person making the withdrawal will be asked
for permission to follow up for 90 and 180 days after randomisation. |
|
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 |