Clinical Trials Register

Summary
EudraCT Number:	2016-003265-26
Sponsor's Protocol Code Number:	345
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2016-11-24
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Austria - BASG

A.2

EudraCT number

2016-003265-26

A.3

Full title of the trial

Pharmacokinetic/Pharmacodynamic effects of add-on antiplatelet therapy with parenteral cangrelor as compared to standard dual antiplatelet treatment in patients with ST-elevation myocardial infarction complicated by out-of-hospital cardiac arrest and treated with targeted temperature management – A Randomized Controlled Trial

Pharmakokinetische / Pharmakodynamische Wirkungen einer zusätzlichen thrombozytenaggregationshemmenden Therapie mit parenteral verabreichbarem Cangrelor im Vergleich zur standardgemäßen oralen dualen Thrombozytenaggregationshemmung bei Patienten mit ST-Strecken-Hebungsinfarkt-assoziiertem Herzkreislaufstillstand unter therapeutischer Hypothermie - Eine randomisierte kontrollierte Studie

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Effect of an additional therapy with the "blood thinner" cangrelor compared to the standard therapy in patients with heart attack caused by myocardial infarction

Wirkung einer zusätzlichen Therapie mit dem "Blutverdünnter" Cangrelor im Vergleich zur Standardtherapie bei Patienten mit Herzinfarkt-bedingtem Herzstillstand

A.3.2

Name or abbreviated title of the trial where available

Add-on Cangrelor in STEMI-triggered Cardiac Arrest

Add-on Cangrelor in STEMI-bedingtem Herzstillstand

A.4.1

Sponsor's protocol code number

345

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Medical University of Vienna
B.1.3.4	Country	Austria
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Medical University of Vienna
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Medical University of Vienna
B.5.2	Functional name of contact point	Department of Emergency Medicine
B.5.3	Address:
B.5.3.1	Street Address	Währinger Gürtel 18-20
B.5.3.2	Town/ city	Vienna
B.5.3.3	Post code	1090
B.5.3.4	Country	Austria
B.5.4	Telephone number	+434040039530
B.5.5	Fax number	+434040019650
B.5.6	E-mail	gabriela.hess@meduniwien.ac.at

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Kengrexal
D.2.1.1.2	Name of the Marketing Authorisation holder	Chiesi Farmaceutici S.p.A. (since 02.09.2016; formerly The Medicines Company UK Ltd)
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Kengrexal
D.3.4	Pharmaceutical form	Powder for concentrate for solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CANGRELOR
D.3.9.1	CAS number	163706-06-7
D.3.9.2	Current sponsor code	Cangrelor
D.3.9.3	Other descriptive name	Cangrelor tetrasodium
D.3.9.4	EV Substance Code	SUB26448
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

ST-elevation myocardial infarction, cardiac arrest

ST-Hebungs-Myokardinfarkt, Herzkreislaufstillstand

E.1.1.1

Medical condition in easily understood language

heart attack, cardiac arrest

Herzinfarkt, Herzstillstand

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the additive platelet suppressing effect of iv P2Y12r inhibitor cangrelor in cardiac arrest patients with STEMI. In particular, the trial aims to investigate whether the additional iv infusion of cangrelor (as “on top treatment”) is superior (i.e. stronger and faster) to the standard oral P2Y12r inhibitor regimen in terms of suppressing ADP-dependent platelet activation at the time of cardiac intervention (i.e. stent placement) in out-of-hospital cardiac arrest (OHCA) patients with STEMI treated with therapeutic hypothermia (TH).

Untersuchung der thrombozytenaggregationshemmenden Wirkung des iv P2Y12r Inhibitors Cangrelor in Patienten mit STEMI assoziiertem Herzkreislaufstillstand. Die Studie soll untersuchen, ob die zusätzliche iv-Infusion von Cangrelor (als "on-top" Behandlung) der oralen Standard P2Y12r-Inhibitor-Therapie in Bezug auf das Ausmaß der Thrombozytenaggregationshemmung zum Zeitpunkt der Herzkranzgefäß-Intervention (d.h. Stentimplantation) in reanimierten Patienten mit STEMI, welche mit therapeutischer Hypothermie behandelt (TH) werden, überlegen ist (dh stärker und schneller eintritt).

E.2.2

Secondary objectives of the trial

Pharmacokinetic profile of cangrelor, prasugrel and ticagrelor in cardiac arrest patients wit STEMI treated with therapeutic hypothermia

Cangrelor safety

Pharmakokinetik von Cangrelor, Prasugrel und Ticagrelor in reanimierten Patienten mit Herzinfarkt, welche mit therapeutischer Hypothermie behandelt werden.

Cangrelor Anwendungssicherheit

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Age 18-74 years
• Comatose survivors of OHCA
• Estimated interval of <10 min from cardiac arrest to initiation of cardiopulmonary resuscitation (no-flow interval)
• Interval of <60 min from initiation of cardiopulmonary resuscitation to ROSC (low-flow interval)
• Initial shockable rhythm (i.e. ventricular fibrillation or pulseless ventricular tachycardia)
• Application of TTM (32–34°C target temperature)
• Diagnosis of ST elevation myocardial infarction (post-ROSC electrocardiography)
• Scheduled for PCI
• Eligible for treatment with standard loading doses of DAPT including acetylsalicylic acid and either prasugrel or ticagrelor

Alter 18 - 74 Jahre
• Koma nach erfolgreich reanimiertem Herzkreislaufstillstand
• Geschätztes Intervall von <10 min von Herzkreislaufstillstand bis zum Beginn der Herdruckmassage (No-Flow-Intervall)
• Intervall von <60 min vom Beginn der Herzdruckmassage bis zum Wiedererlangen eines Spontankreislaufs (ROSC) (Low-Flow-Intervall)
• Schockbarer Erstrhythmus (d.h. Kammerflimmern oder pulslose ventrikuläre Tachykardie)
• Therapie mit TTM (32-34◦C)
• ST-Hebungsinfarkt (STEMI, im EKG nach Wiedererlangen eines Spontankreislaufs)
• Geplante perkutane Coronarintervention (PCI)
• Geeignet für eine Therapie mit Standarddosen einer DAPT inkl. Acetylsalicylsäure und Prasugrel oder Ticagrelor

E.4

Principal exclusion criteria

• Pregnant or breast-feeding patients
• Body weight <60kg
• Response to verbal commands after ROSC (thus not eligible for TTM)
• Cardiac arrest due to trauma, exsanguination, strangulation, smoke inhalation, drug overdose, electrocution, hanging or drowning, or intracranial hemorrhage
• Patients not achieving ROSC or subjected to an extracorporeal circulatory assist device
• Acute treatment with P2Y12r inhibitor other than prasugrel or ticagrelor
• Active bleeding or increased risk of bleeding because of irreversible coagulation disorders or due to recent major surgery/trauma or uncontrolled severe hypertension
• Known history of ischemic or hemorrhagic stroke or transient ischemic attack (TIA)
• Known history of severe hepatic impairment (Child Pugh C)
• Known history of severe renal impairment (creatinine clearance <30mL/min)
• Hypersensitivity to the active substance or to any of the excipients
• Terminal illness present before cardiac arrest
• Thrombolysis therapy
• Scheduled for coronary bypass surgery (CABG)
• Prior P2Y12r inhibitor use in the past 7 days
• Prior vitamin K antagonists/NOACs use in past 7 days
• Patients with known allergic reaction to P2Y12r inhibitors

• Schwangerschaft / Stillzeit
• Körpergewicht <60 kg
• Reaktion auf verbale Befehle nach Wiedererlangen eines Spontankreislaufs (ungeeignet für TTM)
• Herzstillstand infolge Trauma, Blutung, Strangulation, Rauchgasvergiftung, Medikamentenüberdosierung, Stromschläge, Erhängen, Ertrinken oder Hirnblutungen
• Ausbleiben eines Spontankreislaufs oder Verwendung einer extrakorporalen Herzkreislaufunterstützung
• Behandlung mit Clopidogrel
• Eine aktive Blutung oder erhöhtes Risiko von Blutungen aufgrund von beeinträchtigter Hämostase und/oder irreversiblen Koagulationsstörungen oder kürzlich erfolgten großen chirurgischen Eingriffen/Traumata oder unkontrollierter schwer einstellbarer Hypertonie
• Bekannte Anamnese eines ischämischen oder hämorrhagischen Schlaganfalls oder einer transitorischen ischämischen Attacke (TIA)
• Bekannte Anamnese einer schweren Leberinsuffizienz (Child-Pugh C)
• Bekannte Anamnese einer schweren Niereninsuffizienz (Kreatinin-Clearance <30 ml / min)
• Allergie/Hypersensitivität gegenüber der aktiven Substanz bzw. der Arzneiträgerstoffe
• Bekannte Anamnese einer terminalen unheilbaren (palliativen) Erkrankung
• Thrombolyse-Therapie
• Vorgesehene koronare Bypass-Operation (CABG)
• P2Y12r Inhibitor Einnahme in den letzten 7 Tage
• Vitamin-K-Antagonisten / NOACs Einnahme in den letzten 7 Tagen
• Patienten mit bekannter Allergie auf P2Y12r-Inhibitoren

E.5 End points

E.5.1

Primary end point(s)

Platelet reactivity at the time of cardiac intervention (i.e. at the time of stent placement) measured by impedance aggregometry (Multiplate Analyzer, aggregation units/min, AU*min).

ADP-abhängige Thrombozytenreaktivität zum Zeitpunkt des Coronarstentings gemessen mittels Multiplate Analyzer als Fläche unterhalb der Thrombozytenaggregationskurve angegeben als Aggregation Units (AU) * min

E.5.1.1

Timepoint(s) of evaluation of this end point

at baseline, at the time of stent placement, 15minutes, 30minutes, 60minutes, 120minutes, 240minutes, 360minutes, 12hours and 24hours

Zu Beginn der Studie, die zum Zeitpunkt der Stentimplantation , 15 Minuten, 30 Minuten, 60 Minuten, 120 Minuten 240 Minuten, 360 Minuten, 12 Stunden und 24 Stunden

E.5.2

Secondary end point(s)

Platelet reactivity (ADP-dependent platelet inhibition) at baseline, at the time of stent placement, 15 minutes, 30 minutes, 60 minutes, 120 minutes, 240 minutes and 12 hours after study drug administration (Multiplate Analyzer, VASP assay, PFA-100).

Onset of ADP-dependent platelet inhibition (Multiplate Analyzer, VASP assay, PFA-100). 15 minutes and 30 minutes time points were chosen to exactly identify the onset of ADP-dependent platelet inhibition.

Pharmacokinetic profile of cangrelor, prasugrel and ticagrelor at the time of stent placement, 15 minutes, 30 minutes, 60 minutes, 120 minutes, 240 minutes and 12 hours after study drug administration.

Adverse events (minor and major bleeding, early definite stent thrombosis, stroke, revascularization procedure with PCI or coronary artery bypass grafting), ED/ICU mortality, laboratory safety parameters (CBC, chemistry including troponin, coagulation), time course of TTM (esophageal und urinary bladder temperature)

Thrombozytenreaktivität zu Beginn der Studie, die zum Zeitpunkt der Stentimplantation, 15 Minuten, 30 Minuten, 60 Minuten, 120 Minuten 240 Minuten und 12 Stunden nach Verabreichung der Prüfsubstanz (Multiplate Analyzer, VASP-Assay, PFA-100 ).

Beginn Thrombozytenaggregationshemmung (Multiplate Analyzer, VASP-Assay, PFA-100). 15 Minuten und 30 Minuten Zeitpunkte wurden gewählt, um genau den Beginn der ADP-abhängige Blutplättchenhemmung identifizieren.

Pharmakokinetisches Profil von Cangrelor, Prasugrel und Ticagrelor zum Zeitpunkt der Stentimplantation, 15 Minuten, 30 Minuten, 60 Minuten, 120 Minuten 240 Minuten und 12 Stunden nach Verabreichung der Prüfsubstanz.

Unerwünschte Ereignisse (kleinere und größere Blutungen, frühe definitive Stentthrombose, Schlaganfall, Revaskularisation mittels PCI oder aortokoronarem Bypass), ED / ICU Mortalität, Laborsicherheitsparameter (Blutbild, Chemie, Koagulation), Zeitverlauf von TTM ( Ösophagus und Harnblase Temperatur)

E.5.2.1

Timepoint(s) of evaluation of this end point

at baseline, at the time of stent placement, 15minutes, 30minutes, 60minutes, 120minutes, 240minutes, 360minutes, 12hours and 24hours

zu Beginn der Studie, die zum Zeitpunkt der Stentimplantation , 15 Minuten, 30 Minuten, 60 Minuten, 120 Minuten 240 Minuten, 360 Minuten, 12 Stunden und 24 Stunden

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

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

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2016-11-24.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Out-of-hospital cardiac arrest patients are unconscious and unable to understand the purpose of the study at the moment of inclusion.

Herzstillstand -Patienten sind bewusstlos und nicht in der Lage, Art und Zweck der Studie zum Zeitpunkt der Studieneinschlusses zu verstehen.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Post trial treatment will not differ from the expected normal treatment

Post Trial Behandlung wird nicht von der erwarteten normalen Behandlung abweichen

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-01-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-12-07

P. End of Trial
P.	End of Trial Status	Ongoing

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