CERE-LYSE-1: Combined Treatment With Alteplase (Rt-PA) and Cerebrolysin® in Acute Ischemic Hemispheric Stroke

Sponsor

Ever Neuro Pharma GmbH (Industry)

Overall Status

Completed

CT.gov ID

NCT00840671

Collaborator

JSW-Research Forschungslabor GmbH, Parkring 12, 8074 Grambach (Other)

119

Enrollment

Locations

Arms

Duration (Months)

7.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

It should be shown that Cerebrolysin in combination with Alteplase, the medication that should recover the blood flow through the brain, is an effective and save medication to treat ischeamic stroke.

Condition or Disease	Intervention/Treatment	Phase
Stroke	Drug: Cerebrolysin Drug: 0.9% Saline Solution	Phase 3

Detailed Description

The current trial should evaluate a combined treatment using Cerebrolysin immediately after thrombolysis to guarantee that the neurotrophic components are able to reach the endangered brain areas efficiently. An early start of treatment should guarantee rescue of most of the neurons reducing the overall damage.The study follows the design of pure thrombolytic trials to investigate, if the early neuroprotective treatment with Cerebrolysin is able to improve the overall outcome of patients at the day 90 evaluation visit. Due to the initial findings special emphasis will be also put on analysing the speed of recovery.

Study Design

Study Type:

Interventional

Actual Enrollment :

119 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Prospective, Randomised, Placebo Controlled, Double Blind Trial About Safety and Efficacy of Combined Treatment With Alteplase (Rt-PA) and Cerebrolysin® in Acute Ischemic Hemispheric Stroke

Study Start Date :

Oct 1, 2005

Actual Primary Completion Date :

Mar 1, 2008

Actual Study Completion Date :

Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cerebrolysin Cerebrolysin, 30 ml/day as intravenous infusion, first infusion after completion of thrombolytic therapy. Daily infusion for 10 consecutive days.	Drug: Cerebrolysin Cerebrolysin, 30 ml/day as intravenous infusion, first infusion after completion of thrombolytic therapy. Daily infusion for 10 consecutive days.
Placebo Comparator: 0.9% Saline Solution 0.9% Saline Solution, 30 ml/day as intravenous infusion, first infusion after completion of thrombolytic therapy. Daily infusion for 10 consecutive days.	Drug: 0.9% Saline Solution 0.9% Saline Solution, 30 ml/day as intravenous infusion, first infusion after completion of thrombolytic therapy. Daily infusion for 10 consecutive days. Other Names: NaCl

Arm

Intervention/Treatment

Experimental: Cerebrolysin

Cerebrolysin, 30 ml/day as intravenous infusion, first infusion after completion of thrombolytic therapy. Daily infusion for 10 consecutive days.

Drug: Cerebrolysin

Cerebrolysin, 30 ml/day as intravenous infusion, first infusion after completion of thrombolytic therapy. Daily infusion for 10 consecutive days.

Placebo Comparator: 0.9% Saline Solution

0.9% Saline Solution, 30 ml/day as intravenous infusion, first infusion after completion of thrombolytic therapy. Daily infusion for 10 consecutive days.

Drug: 0.9% Saline Solution

0.9% Saline Solution, 30 ml/day as intravenous infusion, first infusion after completion of thrombolytic therapy. Daily infusion for 10 consecutive days.

Other Names:

NaCl

Outcome Measures

Primary Outcome Measures

Modified Rankin Scale score at day 90 (or earlier in the event of patient withdrawal). [Day 90]

Secondary Outcome Measures

NIH Stroke Scale Score 90 days after start of treatment (or earlier in the event of patient withdrawal). Actual score or change from baseline score analysed. [90 days after start of treatment]
Glasgow Outcome Score 90 days after start of treatment (or earlier in the event of patient withdrawal). Actual score or change from baseline score analysed. [90 days after start of treatment]
Barthel Index Score 90 days after start of treatment (or earlier in the event of patient withdrawal). Actual score or change from baseline score analysed. [90 days after start of treatment]
Responders classified according to Barthel Index Score ≥95, Glasgow Outcome Score 0-1, NIHSS change from baseline score, 8 point improvement or total score 0-1 or NIHSS Distal Motor Function Score 0-1. Responder rates across each scale analysed. []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Female or male inpatients.
Age: 18-80 years.
If female, patient must not be pregnant
Clinical diagnosis of ischemic stroke causing a measurable neurological deficit defined as impairment of language, motor function, cognition and/or gaze,vision or neglect. Ischemic stroke is defined as an event characterized by the sudden onset of an acute focal neurologic deficit presumed to be due to cerebral ischemia after CT scan excludes haemorrhage.
Onset of symptoms within 3 hours prior to initiation of rt-PA administration.
Stroke symptoms are to be present for at least 30 minutes and have not significantly improved before treatment. Symptoms must be distinguishable from an episode of generalized ischemia (i.e. syncope), seizure or migraine disorder.
Patient is willing to participate voluntarily and to sign a written patient informed consent. Informed consent will be obtained from each patient or the subject's legally authorized representative or relatives, or deferred where applicable, according to the regulatory and legal requirements of the participating country.
Patients who are unable to sign but who are able to understand the meaning of participation in the study may give an oral witnessed informed consent. These patients have to make clear undoubtful that they are willing to participate voluntarily and must be able to understand an explanation of the contents of the information sheet. A written consent has to be obtained as soon as possible.
Willingness and ability to comply with the protocol.

Exclusion Criteria:

Evidence of intracranial haemorrhage (ICH) on the CT-scan
Violation of inclusion criteria not approved by clinical study director or study safety officer
Failure to perform or to evaluate screening or baseline examinations
Hospitalisation (except for study purposes) or change of concomitant medication 4 weeks prior to screening or during screening period
Participation in another therapeutic clinical trial 3 months before baseline
Patients with any history of prior stroke and concomitant diabetes
Prior stroke within the last 3 months
Platelet count of below 100x103/mm3
Blood glucose <50 or >400 mg/dl (<2.77 or >22.15 mmol/L)
Known haemorrhagic diathesis
Manifest or recent severe or dangerous bleeding
Known bacterial endocarditis, pericarditis
Acute pancreatitis
Documented ulcerative gastrointestinal disease during the last 3 months, oesophageal varices, arterial-aneurysm, arterial/venous malformation
Neoplasm with increased bleeding risk
Severe liver disease, including hepatic failure, cirrhosis, portal hypertension, oesaphageal varices) and active hepatitis
Major surgery or significant trauma in past 3 months
Lab values seriously abnormal, and/or more than 2 lab values abnormal not approved by clinical study director or study safety officer
Serious drug allergies
Hypersensitivity to one of the components of the drug
Severe renal impairment
Systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, or aggressive management (IV medication) necessary to reduce BP to these limits
Recent (less than 10 days) traumatic external heart massage, obstetrical delivery, recent puncture of a non-compressible blood-vessel (e.g. subclavian or jugular vein puncture)
Chronic intoxication or chronic substance use disorder with pharmaceuticals, drugs, alcohol or industrial poisons
Symptoms of ischemic attack began more than 3 hours prior to start of thrombolytic therapy or if time of symptom onset is unknown
Minor neurological deficit or symptoms rapidly improving before start of infusion
Severe stroke as assessed clinically (e.g. NIHSS >25) and/or by appropriate imaging techniques
Epilepsy or epileptic seizure at onset of stroke
Symptoms suggestive of subarachnoid haemorrhage, even if the CT-scan is normal
Known history of or suspected intracranial haemorrhage
Suspected subarachnoid haemorrhage or condition after subarachnoid hemorrhage from aneurysm
Any history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery)
Haemorrhagic retinopathy, e.g. in diabetes (vision disturbances may indicate haemorrhagic retinopathy)
Administration of heparin within the previous 48 hours and a thromboplastin time exceeding the upper limit of normal for laboratory
Patients receiving oral anticoagulants, e.g. warfarin sodium
Special attention should be given to possible additive effects when used in conjunction with anti-depressants or MAO-inhibitors
Cerebrolysin should not be mixed with balanced amino acid solutions in an infusion

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Universitätsklinik Innsbruck, Dept. of Neurology	Innsbruck	Austria	6020
2	LKH Klagenfurt, Abteilung für Neurologie	Klagenfurt	Austria	9020
3	AKH Linz, Abteilung Neurologie & Psychiatrie	Linz	Austria	4021
4	Außenstelle Landesklinikum Donauregion Gugging	Maria Gugging	Austria	3400
5	Krankenhaus der Barmherzigen Brüder/Abteilung für Neurologie	Wien	Austria	1020
6	Klinicka Bolnicki Centar, Klinika za Nevrologiju	Rijeka	Croatia	51000
7	Clinical Hospital Split, Dept. of Neurology	Split	Croatia	21000
8	Medical School of Zagreb	Zagreb	Croatia	10000
9	University Hospital Sorrores Misericoridae	Zagreb	Croatia	10000
10	St. Ann's Hospital, Dept. of Neurology	Brno	Czech Republic	65691
11	Blessed Mary Anthony Hospital, Dept. of Neurology	Ostrava Vitkovice	Czech Republic	70384
12	Clinic of Neurology, Faculty Hospital Ostrava	Ostrava	Czech Republic	70852
13	University Hospital Plzen	Plzen	Czech Republic	30460
14	University Hospital, Comenius University, Dept. of Neurology	Bratislava	Slovakia	81369
15	Clinical Hospital Centre Ljubljana	Ljubljana	Slovenia	1525

Sponsors and Collaborators

Ever Neuro Pharma GmbH
JSW-Research Forschungslabor GmbH, Parkring 12, 8074 Grambach

Investigators

Study Director: Manfred Windisch, PhD, JSW Research Forschungslabor GmbH
Principal Investigator: Wilfried Lang, MD, Krankenhaus der Barmherzigen Brüder, 1020 Wien