Clinical trial NCT00868283: The Safety and Efficacy of Cerebrolysin in Patients With Acute Ischemic Stroke
Official title: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Cerebrolysin in Patients With Acute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Ischemic Stroke
Lead sponsor: Ever Neuro Pharma GmbH
Sponsor class: INDUSTRY
Collaborators: name: Excel PharmaStudies, Inc.
name: idv Datenanalyse und Versuchsplanung
First posted: 2009-03-24
Enrollment: 1071
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study investigated the clinical efficacy and safety of a 10-day course of therapy with daily intravenous administration of 30mL Cerebrolysin based on a comparison with Placebo in patients with acute ischemic stroke. 1070 patients were randomized in this trial in 2 parallel groups, one receiving Cerebrolysin, the control group receiving Placebo. Study drug will be given once daily by intravenous infusion for 10 consecutive days. Acetylsalicylic acid will be given orally, once daily throughout the study duration of 90 days as basic treatment. The clinical observation period for each patient will be 3 months and will include six clinical evaluation visits at Baseline (day 1) and on study days 2, 5, 10, 30 and 90.


Eligibility criteria: Inclusion Criteria:

* Age between 18 and 85 years
* Focal neurological deficit
* Clinical diagnosis of acute hemispheric ischemic stroke
* CT or MRI results compatible with clinical diagnosis of acute hemispheric stroke
* NIH Stroke Scale Score between 6 and 22, both inclusive
* Functionally independent prior to stroke with a pre-stroke Rankin Score of 0 or 1
* Randomization and first treatment with the trial medication within 12h after stroke onset
* Informed consent given by the patient and/or the patient's legally acceptable representative

Exclusion Criteria:

* Evidence on CT/MRI of acute or chronic intracerebral hemorrhage, SAH, AVM, cerebral aneurysm, or neoplasm
* Signs of herniation, increased intracranial pressure or likely etiology other than brain ischemia at baseline CT scan
* Patients with a substantial decrease of consciousness or alertness at the time of randomization, defined as score of 2 or more one of the NIH Stroke Scale questions 1a.
* Neurological signs and symptoms that improve rapidly during screening and are likely to resolve completely within 24h
* Severe coexisting systemic disease that significantly limits life expectancy
* Systolic blood pressure over 220 mmHg or diastolic blood pressure over 120 mmHg on repeated measurement (interval of 30 min) prior to study entry
* Severe congestive heart failure or presentation with acute myocardial infarction at study entry
* Epilepsy or epileptic seizures at onset of stroke
* Pre-existing disorders or conditions that would impair interpretation of neurological assessment (eg. severe dementia, severe psychiatric illnesses, etc).
* Concomitant treatment with other neuroprotective or nootropic drugs (e.g. piracetam, citicoline, investigational neuroprotective substances)
* Patients which cannot tolerate or have contraindication to aspirin or Cerebrolysin treatment
* Concomitant treatment with substances that have a dilative effect on blood vessels like naftidrofuryl, cinnarizine, flunarizine or nimodipine
* Pregnancy and lactation period; for women with child-bearing potential a negative pregnancy test is required
* Participation in a clinical trial with an investigational drug in the past 4 weeks

Primary outcomes:
measure: Modified Rankin Scale
timeFrame: 90 days after start of treatment
measure: Barthel Index
timeFrame: 90 days after start of treatment
measure: NIH Stroke Scale
timeFrame: 90 days after start of treatment
Secondary outcomes:
measure: SF-12
timeFrame: 90 days after start of treatment
measure: Overall mortality
timeFrame: Throughout the study
Other outcomes:
Locations:
city: Mudanjiang
country: China
facility: Mudanjiang 1st people Hospital
state: Heilongjiang
city: Mudanjiang
country: China
facility: Mudanjiang 2nd people Hospital
state: Heilongjiang
city: Anhui
country: China
facility: Anhui Shengli Hospital
city: Anshan
country: China
facility: Anshan hospital
city: Baotou
country: China
facility: Baotou Center Hospital
city: Baotou
country: China
facility: Third hospital, affiliated Neimenggu Medical University (Bao Gang hospital)
city: Beijing
country: China
facility: Beijing PLA General Hospital
city: Beijing
country: China
facility: First hospital, affiliated Peking University
city: Beijing
country: China
facility: Friendship Hospital, affiliated Capital Medical University
city: Beijing
country: China
facility: Peking Anzhen Hospital
city: Beijing
country: China
facility: Sino-Japanese Friendship Hospital
city: Canton
country: China
facility: Guangzhou 2nd People's Hospital
city: Changchun
country: China
facility: First hospital, affiliated Bethune Medical University
city: Changchun
country: China
facility: Second Hospital Affiliated Bethune Medical University
city: Changsha
country: China
facility: Xiangya Hospital, affiliated Hunan Medical University
city: Chengdu
country: China
facility: Chengdu 2nd People's Hospital
city: Chengdu
country: China
facility: First Hospital, affiliated Huaxi Medical University
city: Chengdu
country: China
facility: Sichuan Province People's Hospital
city: Chongqing
country: China
facility: Second Hospital, affiliated Chongqing Med. University
city: Dalian
country: China
facility: Dalian Center Hospital
city: Dalian
country: China
facility: Dalian third people Hospital
city: Dalian
country: China
facility: Second Hospital, affiliated Wenzhou Med. University
city: Fuzhou
country: China
facility: First hospital, affiliated Fujian Medical University
city: Fuzhou
country: China
facility: FuJian Shengli Hospital
city: Guandong
country: China
facility: First Hospital, affiliated Shantou Medical University
city: Guangzhou
country: China
facility: Guangzhou red cross hospital
city: Hangzhou
country: China
facility: First Hospital, affiliated Medical college Zhejing University
city: Harbin
country: China
facility: The 4st Hospital affiliated Harbin Medical University
city: Kunming
country: China
facility: Second Hospital, affiliated Kunming Med. University
city: Mudanjiang
country: China
facility: Yinchuan People's Hospital
city: Nanjing
country: China
facility: Nanjing PLA General Hospital
city: Nanjing
country: China
facility: Zhongda Hospital
city: Qingdao
country: China
facility: First Hospital, affiliated Qingdao Medical University
city: Shanghai
country: China
facility: Huashan Hospital, affiliated Fudan University
city: Shanghai
country: China
facility: Renji Hospital, affiliated Second Medical University
city: Shanghai
country: China
facility: Ruijin Hospital, affiliated Jiaotong University
city: Shanghai
country: China
facility: Shanghai 6th People's Hospital
city: Shanghai
country: China
facility: Xinhua hospital of Shanghai Jiaotong University School of Medicine
city: Shanghai
country: China
facility: Zhongshan Hospital, affiliated Fudan University
city: Shijiazhuang
country: China
facility: Hebei Province People's Hospital
city: Tianjin
country: China
facility: Tianjin First Medical Center
city: Tianjin
country: China
facility: Tianjin Union Medicine Centre
city: Wuhan
country: China
facility: Union Hospital, affiliated Huazhong science and technology University
city: Yinchuan
country: China
facility: First hospital, affiliated NingXia Mededical University
city: Zhengzhou
country: China
facility: First hospital, affiliated Henan Medical University
city: Hong Kong
country: Hong Kong
facility: Chinese University of Hong Kong
city: Seoul
country: Korea, Republic of
facility: Asan medical center
city: Seoul
country: Korea, Republic of
facility: East-west neo medical center
city: Seoul
country: Korea, Republic of
facility: Kyung-hee University Hospital
Study officials:
affiliation: EVER Neuro Pharma
name: Philipp Novak, PhD
role: STUDY_DIRECTOR
affiliation: Huashan Hospital, affiliated Fudan University
name: Zhen Hong, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hong Z, Moessler H, Bornstein N, Brainin M, Heiss WD; CASTA-Investigators. A double-blind, placebo-controlled, randomized trial to evaluate the safety and efficacy of Cerebrolysin in patients with acute ischaemic stroke in Asia--CASTA. Int J Stroke. 2009 Oct;4(5):406-12. doi: 10.1111/j.1747-4949.2009.00340.x.
citation: Heiss WD, Brainin M, Bornstein NM, Tuomilehto J, Hong Z; Cerebrolysin Acute Stroke Treatment in Asia (CASTA) Investigators. Cerebrolysin in patients with acute ischemic stroke in Asia: results of a double-blind, placebo-controlled randomized trial. Stroke. 2012 Mar;43(3):630-6. doi: 10.1161/STROKEAHA.111.628537. Epub 2012 Jan 26.
citation: Bornstein NM, Guekht A, Vester J, Heiss WD, Gusev E, Homberg V, Rahlfs VW, Bajenaru O, Popescu BO, Muresanu D. Safety and efficacy of Cerebrolysin in early post-stroke recovery: a meta-analysis of nine randomized clinical trials. Neurol Sci. 2018 Apr;39(4):629-640. doi: 10.1007/s10072-017-3214-0. Epub 2017 Dec 16.