Clinical Trials Register

Summary
EudraCT Number:	2009-017454-12
Sponsor's Protocol Code Number:	U01–NS052220
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2010-12-15
Trial 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

Netherlands - Competent Authority

A.2

EudraCT number

2009-017454-12

A.3

Full title of the trial

INTERVENTIONAL MANAGEMENT OF STROKE TRIAL CLINICAL PROTOCOL
A phase III, randomized, multi-center, open label, 900 subject clinical trial that will examine whether a combined intravenous (IV) and intra-arterial (IA) approach to recanalization is superior to standard IV rt-PA (Activase®/Actilyse®) alone when initiated within three hours of acute ischemic stroke onset.

KLINISCH PROTOCOL VOOR ONDERZOEK NAAR CVA-MANAGEMENT MET INTERVENTIE - IMS III
CVA-management met interventie – IMS III-onderzoek – fase III, gerandomiseerd, multi-centrisch, open klinisch onderzoek onder 900 patiënten met een ischemische beroerte, waarbij onderzocht moet worden of, met het oog op het opnieuw doorlaatbaar maken van het getroffen bloedvat, de gecombineerde intraveneuze/intra-arteriële toediening van rt-PA (Actilyse®) binnen de eerste drie uur na aanvang van de symptomen beter is dan de huidige uitsluitend intraveneuze toediening van rt-PA (Actilyse®).

A.3.1

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

INTERVENTIONAL MANAGEMENT OF STROKE TRIAL CLINICAL PROTOCOL
(IMS III study)

KLINISCH PROTOCOL VOOR ONDERZOEK NAAR CVA-MANAGEMENT MET INTERVENTIE - IMS III

A.3.2

Name or abbreviated title of the trial where available

IMS III

A.4.1

Sponsor's protocol code number

U01–NS052220

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00359424

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	University of Cincinnati - Academic Medical Center -Department of Neurology
B.1.3.4	Country	United States
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	National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Health (NIH)
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University of Cincinnati - Academic Medical Center -Department of Neurology
B.5.2	Functional name of contact point	Joseph P. Broderick
B.5.3	Address:
B.5.3.1	Street Address	260 Stetson Street, Suite 2300
B.5.3.2	Town/ city	Cincinnati - Ohio
B.5.3.3	Post code	45267-0525
B.5.3.4	Country	United States
B.5.4	Telephone number	+1513558-5429
B.5.5	Fax number	+1513558-1712
B.5.6	E-mail	BRODERJP@UCMAIL.UC.EDU

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	Actilyse
D.2.1.1.2	Name of the Marketing Authorisation holder	BOEHRINGER INGELHEIM bv
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	Actilyse
D.3.4	Pharmaceutical form	Powder and solvent for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Parenteral use (Noncurrent) Intravenous drip use (Noncurrent) Intravenous bolus use (Noncurrent) Intraarterial use Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ALTEPLASE
D.3.9.1	CAS number	105857236
D.3.9.2	Current sponsor code	Actilyse
D.3.9.3	Other descriptive name	rt-PA
D.3.10	Strength
D.3.10.1	Concentration unit	mg/l milligram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Actilyse
D.2.1.1.2	Name of the Marketing Authorisation holder	BOEHRINGER INGELHEIM bv
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	Actilyse
D.3.4	Pharmaceutical form	Powder and solvent for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous drip use (Noncurrent) Intravenous bolus use (Noncurrent) Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ALTEPLASE
D.3.9.1	CAS number	105857236
D.3.9.2	Current sponsor code	Actilyse
D.3.9.3	Other descriptive name	rt-PA
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Ischemic Stroke

ischemische beroerte

E.1.1.1

Medical condition in easily understood language

Ischemic Stroke

ischemische beroerte

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10065528
E.1.2	Term	NIH stroke scale score increased
E.1.2	System Organ Class	10022891 - Investigations

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10055221
E.1.2	Term	Ischemic stroke
E.1.2	System Organ Class	10029205 - Nervous system disorders

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 determine if ischemic stroke subjects with a baseline NIH Stroke Scale Score ≥ 10 (8-9 with positive CTA) treated with recombinant tissue plasminogen activator (rt-PA; [Alteplase recombinant], Actilyse® Boehringer Ingelheim ) utilizing a combined intravenous plus intra-arterial (IV/IA) approach to recanalization started within 3 hours of onset, are more likely to have a favorable outcome at 3 months, defined as a modified Rankin score of 0-2, as compared to subjects treated with standard IV rt-PA alone.

In dit IMS III-onderzoek zal systematisch onderzocht worden of beroertepatiënten met een uitgangswaarde van ≥ 10 op de NIH Stroke Scale Score (8-9 bij een positieve CT-angiografie), die in de eerste 3 uur na aanvang van de symptomen een gecombineerde intraveneuze (IV)/intra-arteriële(IA) behandeling met Actilyse® krijgen, een beter klinisch verloop vertonen (gedefinieerd als een modified Rankin Score van 0-2 na 3 maanden) dan beroertepatiënten die in de eerste 3 uur na aanvang van de symptomen uitsluitend een intraveneuze behandeling met Actilyse® krijgen.

E.2.2

Secondary objectives of the trial

1. To compare the safety of a combined IV/IA approach to IV rt-PA alone. The primary measures of safety will be mortality at 3 months and occurrence of treatment-related symptomatic intracranial hemorrhage (ICH) confirmed within 24 hours.
2. To evaluate the effectiveness of a combined IV/IA approach as compared to standard IV rt-PA by a number of secondary outcome measures.
3. Cost effectiveness of the combined IV/IA approach as compared to standard IV rt-PA as measured by differences in utilization of resources and quality of life over 12 months between the two arms of the trial
4. To develop and maintain a network of interventional centers

1. Vergelijken van de veiligheid van een gecombineerde IV/IA–toediening in vergelijking met uitsluitend IV-toediening.
Ter beoordeling hiervan worden de sterfte na 3 maanden en het optreden van met de behandeling samenhangende, symptomatische, intracraniale bloedingen binnen 24 uur na de behandeling betrokken.
2. Beoordelen van de efficiëntie van een gecombineerde IV/IA–toediening in vergelijking met uitsluitend IV–toediening aan de hand van een aantal secundaire ontwikkelingsparameters.
3. kostenefficiëntie van een gecombineerde behandeling in vergelijking met een uitsluitend intraveneuze toediening aan de hand van de volgende parameters: kosten en kwaliteit van leven in de 12 maanden na de behandeling.
4. Opzetten en uitbouwen van een netwerk van klinische interventiecentra

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Age: 18 through 82 years (i.e., candidates must have had their 18PthP birthday, but not had their 83rd birthday).
• Initiation of IV rt-PA within 3 hours of onset of stroke symptoms. Time of onset is defined as the last time when the patient was witnessed to be at baseline (i.e., subjects who have stroke symptoms upon awakening will be considered to have their onset at beginning of sleep).
• An NIHSSS ≥ 10 at the time that IV rt-PA is begun or an NIHSSS >7 and <10 with an occlusion seen in M1, ICA or basilar artery on CTA at institutions where baseline CTA imaging is standard of care for acute stroke patients.
• Investigator verification that the subject has received/ is receiving the correct IV rt-PA dose for the estimated weight prior to randomization

- Leeftijd: 18 tot en met 82 jaar (d.w.z.: kandidaten moeten hun 18e verjaardag gehad hebben, maar mogen nog geen 83 jaar geworden zijn)
• Starten met intraveneuze rt-PA binnen 3 uur na het begin van de CVA-symptomen. De tijd waarop de verschijnselen zich begonnen voor te doen wordt bepaald als de laatste keer dat de patiënt op zijn baseline gezien is
• Een NIHSSS-score > 10 op het moment dat wordt begonnen met intraveneus rt-PA of een NIHSSS >7 en <10 met een occlusie in M1, ICA of de basilarie arterie zichtbaar op CTA bij instellingen waar het maken van een baseline-CTA de standaard is in de zorg voor acute CVA-patiënten.
• Controle door de onderzoeker of de persoon de juiste IV rt-PA-dosis krijgt/gekregen heeft voor zijn geschatte gewicht, voorafgaand aan de randomisatie

E.4

Principal exclusion criteria

• History of stroke in the past 3 months.
• Previous intra-cranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arteriovenous malformation.
• Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT scan is normal.
• Hypertension at time of treatment; systolic BP > 185 or diastolic > 110 mm Hg; or aggressive measures to lower blood pressure to below these limits are needed.
• Presumed septic embolus, or suspicion of bacterial endocarditis
• Presumed pericarditis including pericarditis after acute myocardial infarction.
• Suspicion of aortic dissection
• Recent (within 30 days) surgery or biopsy of parenchymal organ.
• Recent (within 30 days) trauma, with internal injuries or ulcerative wounds.
• Recent (within 90 days) severe head trauma or head trauma with loss of consciousness.
• Any active or recent (within 30 days) hemorrhage.
• Patients with known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; or oral anticoagulant therapy require coagulation lab results prior to enrollment. Any subject with INR greater than 1.7 or institutionally equivalent prothrombin time is excluded. Patients without history or suspicion of coagulopathy do not require INR or prothrombin time lab results to be available prior to enrollment.
• Females of childbearing potential who are known to be pregnant and/or lactating or who have positive pregnancy tests on admission.
• Baseline lab values: glucose < 50 mg/dl or > 400 mg/dl, platelets <100,000, or Hct <25
• Patients that require hemodialysis or peritoneal dialysis, or who have a contraindication to an angiogram for whatever reason.
• Patients who have received heparin or a direct thrombin inhibitor (Angiomax™, argatroban, Refludan™, Pradaxa) within the last 48 hours; must have a normal partial thromboplastin time (PTT) to be eligible.
• Subjects with an arterial puncture at a non-compressible site or a lumbar puncture in the previous 7 days.
• Patients with a seizure at onset of stroke
• Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, mRS score at baseline must be ≤ 2. This excludes patients who live in a nursing home or who are not fully independent for activities of daily living (toileting, dressing, eating, cooking and preparing meals, etc.)
• Other serious, advanced, or terminal illness.
• Any other condition that the investigator feels would pose a significant hazard to the patient if Activase/Actilyse® (Alteplase) therapy is initiated.
• Current participation in another research drug treatment.
• Informed consent is not or cannot be obtained. For example, obtunded patients are not automatically excluded from the study. However, if the next of kin or legal guardian (i.e., the individual legally empowered in the state where the consent is obtained) cannot provide consent, randomization and entry into the study could not proceed.
Imaging Exclusion Criteria
• High density lesion consistent with hemorrhage of any degree.
• Significant mass effect with midline shift.
• Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline imaging. An ASPECTS of < 4can be used as a guideline when evaluating >1/3 region of territory involvement. Sulcal effacement and / or loss of grey-white differentiation alone are not contraindications for treatment.
• CT evidence of intraparenchymal tumor
• CT evidence of intraparenchymal tumor
- Baseline CTA without evidence of an arterial occlusion. (NOTE: The study does not require baseline CTA imaging, if CTA is routinely performed prior to IV rt-PA lesion information obtained should be used
to satisfy this exclusion)

• Geschiedenis van CVA in de afgelopen 3 maanden
• Eerdere intra-craniale bloeding, neoplasma, subarachnoïdale bloeding of arterioveneuze misvorming
• Klinisch beeld suggereert een subarachnoïdale bloeding, ook al is de eerste CT-scan normaal
• Hypertensie op het moment van behandelen; bloeddruk systolisch> 185 of diastolisch > 110 mm Hg) of agressieve maatregelen nodig om de bloeddruk onder deze grenzen te krijgen.
• Veronderstelde septische embolus, of vermoeden van bacteriële endocarditis
• Veronderstelde pericarditis, inclusief pericarditis na acuut MI
• Vermoeden van een aortadissectie
• Recente (30 dagen of minder geleden) operatie aan of biopsie van parenchym orgaan
• Recent (30 dagen oud of minder) trauma, met inwendig letsel of ulcererende wonden
• Recent (90 dagen oud of minder) ernstig hoofdtrauma of hoofdtrauma met verlies van bewustzijn
• Enige actieve of recente (30 dagen of minder geleden) bloeding
• Patiënten met bekende erfelijke of verworven hemorragische diathese, stollingsfactordeficiëntie of orale antistollingstherapie dienen voor opname in het onderzoek stollingstests te ondergaan. Iedereen met INR > 1,7 of het in de instelling gebruikte equivalent aan protrombinetijd is uitgesloten. Voor patiënten zonder geschiedenis of vermoeden van coagulopathie zijn geen laboratoriumtests naar INR-waarde of protrombinetijd nodig voor opname in het onderzoek.
• Vrouwen in de vruchtbare leeftijd van wie bekend is dat ze zwanger zijn en/of borstvoeding geven of bij wie een zwangerschapstest positief is
• Baseline laboratoriumwaarden: glucose < 50 mg/dl of > 400 mg/dl, bloedplaatjes <100.000, of Hct <25%
• Patiënten die hemodialyse of peritoneale dialyse ondergaan, of die contrageïndiceerd zijn voor angiogrammen
• Patiënten die heparine of een directe trombine-inhibitor gekregen hebben (Angiomax™, argatroban, Refludan™, Pradaxa) binnen 48 uur moeten een normale partiële tromboplastinetijd (PTT) hebben om in aanmerking te komen
• Patiënten die in de afgelopen 7 dagen een arteriële punctie op een niet-compressibele plaats of een lumbaalpunctie hebben ondergaan
• Patiënten met een insult tijdens het begin van de beroerte
• Patiënten met een reeds bestaande neurologische of psychiatrische aandoening die de neurologische of functionele beoordelingen kan vertroebelen, de mRS-score op de baseline moet < 2 zijn. Dit sluit patiënten uit die in een verpleeghuis wonen of die voor de algemene dagelijkse handelingen (toiletbezoek, aan- en uitkleden, eten, koken, maaltijden voorbereiden etc.) niet volledig onafhankelijk zijn.
• Andere ernstige, gevorderde of terminale ziekten
• Elke andere afwijking die volgens de onderzoeker een significant risico vormt voor de patiënt als er begonnen wordt met de Activase®/Actilyse® (Alteplase)-behandeling
• Huidige deelname aan een ander onderzoeksprogramma naar behandeling met medicatie
• De onmogelijkheid een geschreven geïnformeerde toestemming (informed consent) te verkrijgen zoals die volgens de ter plaatse geldende regels vereist is.

CT-scan exclusiecriteria
• Hyperdense lesie, overeenkomend met enige graad van bloeding
• Significante ruimte innemende massa met verschuiving van de middellijn
• Grote (>1/3 van de middelste hersenarterie) gebieden met duidelijke hypodensiteit op de baseline CT-scan. (ASPECTS < 4 kan dienen als richtlijn) Verminderde sulcus en/of verlies van grijs-wit differentiatie zijn geen contra-indicaties voor deelname
• CT-aanwijzing voor intraparenchymale tumor
- Uitgangs-CTA zonder aanwijzingen voor occlusie van een aterieel bloedvat. (LET OP: Voor het onderzoek is geen uitgangs-CTA-scan nodig, maar als CTA standaard wordt gemaakt voorafgaand aan rt-PA iv, dient de verkregen informatie over de laesie te worden gebruikt om te voldoen aan dit exclusiecriterium)

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy outcome measure is the modified Rankin Scale (mRS) score, dichotomized to 0-2 versus greater than 2, at 3 months from randomization.

Tijdens dit onderzoek zal onderzocht worden of beroertepatiënten met een uitgangswaarde van ≥ 10 op de NIH Stroke Scale Score (8-9 bij een positieve CT-angiografie), die in de eerste 3 uur na aanvang van de symptomen een intraveneuze(IV)/intra-arteriële(IA) combinatiebehandeling met Actilyse® krijgen, een beter klinisch verloop vertonen (gedefinieerd als een modified Rankin Score van 0-2 na 3 maanden) dan beroertepatiënten die in de eerste 3 uur na aanvang van de symptomen uitsluitend een intraveneuze behandeling met Actilyse® krijgen.

E.5.1.1

Timepoint(s) of evaluation of this end point

3 months from randomization

3 maanden na randomisatie

E.5.2

Secondary end point(s)

1. Barthel Index
2. NIHSSS
3. Trail Making Test at 3 months
4. Early Response to treatment as determined by an NIHSSS of 02- at 24
hours from randomization
5. Dichotomized mRS score (0-2 versus 3-6) at 6 months, 9 months and 12 months

Satefy Outcomes: Death, Incidence of Intracranial hemorrhage

1. Barthel Index
2. NIHSSS
3. Trail Making Test na 3 maanden
4. Vroeg reactie op de behandeling, zoals bepaald door een NIHSSS van 02 - op 24 uur
na randomisatie
5. Dichotomized mRS score (0-2 versus 3-6) na 6 maanden, 9 maanden en
12 maanden
Veiligheid resultaten: De dood, incidentie van intracraniale bloeding

E.5.2.1

Timepoint(s) of evaluation of this end point

at 24 hours, 3 months, 6 months, 9 months and 12 months

na 24 uur, 3 maanden, 6 maanden, 9 maanden en 12 maanden

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

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)

Yes

E.7.4

Therapeutic use (Phase IV)

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

E.8.1.4

Double blind

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Hetzelfde geneesmiddel

Same medicinal product

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Canada

France

Germany

Netherlands

Spain

Switzerland

United States

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

last visit of the last subject undergoing the trial

laatste bezoek van het laatste patient ondergaat de proef

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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:

300

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

600

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 2010-12-15.

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

Due to the ischemic stroke subjects may be incapable of giving informed consent personally. Following the EC approved institutional practice at each study site provisions will be made to obtain consent from the subject's legal representative.

Vakken kunnen niet in staat zijn het geven van geïnformeerde toestemming persoonlijk. Op elk onderzoek plaatse voorzieningen zal worden gedaan om toestemming te verkrijgen van de wettelijke vertegenwoordiger van het onderwerp.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

100

F.4.2.2

In the whole clinical trial

900

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)

Standard medical treatment for the patient's condition

Standaard medische behandeling voor de toestand van de patiënt

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

2010-12-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-04-21

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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