MACSI: Efficacy and Safety Study of DP-b99 in Treating Acute Ischemic Stroke

Sponsor

D-Pharm Ltd. (Industry)

Overall Status

Terminated

CT.gov ID

NCT00893867

Collaborator

(none)

446

Enrollment

154

Locations

Arms

Duration (Months)

2.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this trial is to determine if intravenous administration of the metal ion trapping agent DP-b99 up to 9 hours following acute ischemic stroke onset, and then for 3 additional days (4 consecutive days in total) is effective in improving long term outcome. Patients will be followed up for 3 months after the stroke.

Condition or Disease	Intervention/Treatment	Phase
Acute Ischemic Stroke	Drug: DP-b99 Drug: Placebo	Phase 3

Detailed Description

This will be a randomized, double-blind, placebo-controlled, multicenter, multi-national, parallel-arm, pivotal study comparing a placebo group to a DP-b99 group treated with intravenous 1.0 mg/kg/d for 4 consecutive days, in acute ischemic stroke patients with an entry National Institutes of Health Stroke Scale (NIHSS) score of 10-16 and a clinical syndrome that includes at least 1 of the following: language dysfunction, visual field defect or Extinction and Inattention (formerly Neglect) (as reflected by at least 1 point on any of the corresponding items of the NIHSS: 9, 3 or 11). An interim analysis for futility will be performed after Day 90 (or last available observation) primary endpoint data have been collected on about 45% of subjects planned to be enrolled. Clinical trial material (CTM) will be administered within 9 hours after the onset of acute ischemic stroke symptoms. Subjects will be randomized at a ratio of 1:1 to receive either DP-b99 or placebo. A data and safety monitoring board (DSMB) will assess the accumulating safety data periodically and will oversee the interim futility analysis.

Study Design

Study Type:

Interventional

Actual Enrollment :

446 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Double Blind, Randomized, Placebo-controlled, Parallel Group, Multicenter Phase 3 Pivotal Study to Assess the Safety and Efficacy of 1mg/kg/Day Intravenous DP-b99 Over 4 Consecutive Days Versus Placebo When Initiated Within Nine Hours of Acute Ischemic Stroke Onset

Study Start Date :

Dec 1, 2009

Actual Primary Completion Date :

Apr 1, 2012

Actual Study Completion Date :

Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DP-b99	Drug: DP-b99 1mg/kg/day over 4 consecutive days given intravenously and initiated up to 9 hours following acute stroke onset.
Placebo Comparator: Mannitol	Drug: Placebo 1mg/kg/day over 4 consecutive days given intravenously and initiated up to 9 hours following acute stroke onset.

Arm

Intervention/Treatment

Experimental: DP-b99

Drug: DP-b99

1mg/kg/day over 4 consecutive days given intravenously and initiated up to 9 hours following acute stroke onset.

Placebo Comparator: Mannitol

Drug: Placebo

1mg/kg/day over 4 consecutive days given intravenously and initiated up to 9 hours following acute stroke onset.

Outcome Measures

Primary Outcome Measures

Modified Rankin Scale (mRS) categorical analysis ("shift") [90 days]

Secondary Outcome Measures

Recovery, defined as a score of ≤ 1 on modified Rankin Score [90 days]
Safety and tolerability [throughout study - baseline until day 90]
the numbers of patients with treatment-emergent adverse events, results of physical examination, 12-lead electrocardiogram, vital signs and laboratory tests (complete blood count, chemistry and urinalysis)
recovery as assessed by an NIHSS of not more than 1 [90 days]
'home time' [90 days]
exploratory endpoint of 'home time', which measures the length of time (as number of nights)spent at home/relatives' home between hospital discharge and day 90

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

M or F age 18 - 85, inclusive
Suffered an acute, likely hemispheric, ischemic stroke, defined as acute, focal, neurological deficit(s), secondary to a presumed vascular event, which must include at least one of the following components (as reflected by at least 1 point on any of the corresponding items of the NIHSS: 3, 9 or 11):

Visual
Best Language
Extinction and Inattention (formerly Neglect)

Suffered the onset of an acute ischemic stroke that can be evaluated and treatment initiated within 9 hours after the onset of acute ischemic stroke symptoms.
Screening NIHSS score of 10 to 16, inclusive
Readily accessible peripheral venous access for clinical trial material (CTM) administration and blood sampling
Ability to understand the requirements of the study and be willing to provide written informed consent as evidenced by signature on an informed consent document approved by an institutional review board or independent ethics committee, and agree to abide by the study restrictions and return for the required assessments.
Provided written authorization for use and disclosure of protected health information in accordance with the Health Insurance Portability and Accountability Act in the United States and the Personal Information Protection and Electronic Documents Act in Canada

Exclusion Criteria:

An intracerebral or subarachnoid hemorrhage per screening/baseline computerized tomography scan or susceptibility-weighted magnetic resonance imaging
A candidate for either:
thrombolytic therapy, or have been treated with thrombolytic therapy for the current stroke
mechanical thromboembolectomy, or have been treated with mechanical thromboembolectomy for the current stroke
Delirious, comatose or stuporous or demented, or having a mental impairment that in the investigator's opinion renders the subject incapable to participate in the study
Have seizure(s) anytime from stroke onset to screening/baseline NIHSS evaluation
Neurological or non-neurological comorbidities that in the investigator's opinion may lead, independent of the current stroke, to further deterioration in the subject's neurological status during the trial period, or may render the study's neurological assessments inconclusive for the purpose of evaluating solely the stroke's effects
Likely to undergo a procedure involving cardiopulmonary bypass during the study period
Suffered a myocardial infarction in the last 90 days
Any medical condition that in the investigator's opinion may threaten the subject's ability to complete the study (e.g., concurrent significant or life-threatening diseases, such as malignancies or end stage organ failure)
Rapid spontaneous improvement of neurological signs during screening/baseline assessments
Premorbid neurological deficits and functional limitations assessed by a pre-stroke Modified Rankin Scale score of > 1
Suffered a stroke within 90 days of the screening/baseline assessments that is either diagnostically confirmed or assumed to be in the same cerebral territory as is the current acute stroke
Either severe hypertension or hypotension, as measured by at least 2 consecutive supine measurements taken 10 minutes apart prior to randomization.
Significant current renal or hepatic disease(s): a serum creatinine concentration of

2.5 mg/dL; alanine aminotransferase, aspartate aminotransferase, or gamma-glutamyl transferase values that are three times greater than the upper limit of normal.

Have a platelet count of <100,000/mm3 or, for patients on oral anticoagulants at study entry, INR of >4
Female of childbearing potential who is not willing to use adequate and effective birth control measures for the duration of the trial. Effective birth control measures include hormonal contraception, a barrier method such as a diaphragm, intrauterine device and/or condom with spermicide
Positive urine pregnancy test at screening/baseline or be a lactating female
Currently dependent on, or abusing, alcohol or one or more of the following: sympathomimetic amines, cannabis, cocaine, hallucinogens, inhalants, opioids, phencyclidine, sedatives and hypnotics
Received an investigational drug or product or participated in an investigational drug study within a period of 30 days prior to receiving study medication or have previously participated in a clinical trial involving DP-b99
Severe anemia as measured by a hemoglobin value of < 7 g/dl.
In a dependent relationship with the physician or the study sponsor.
Known hypersensitivity to any component of the investigational product.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Center of Southern California	Oceanside	California	United States
2	Associated Neurologists, P.C.	Danbury	Connecticut	United States
3	Memorial Health University Medical Center	Savannah	Georgia	United States
4	The University of Kentucky The Methodist Hospital	Lexington	Kentucky	United States
5	University of Louisville, Kentucky Neuroscience Research	Louisville	Kentucky	United States
6	Tufts Medical Center	Boston	Massachusetts	United States
7	Capital Health Regional Medical Center Neuroscience Institute	Trenton	New Jersey	United States
8	Presbitarian Hospital	Charlotte	North Carolina	United States
9	St. Elizabeth's Medical Center	Youngstown	Ohio	United States
10	Legacy Meridian Park Medical Center	Tualatin	Oregon	United States
11	Thomas Jefferson University	Philadelphia	Pennsylvania	United States
12	The Methodist Hospital	Houston	Texas	United States
13	Carilion Clinic	Roanoke	Virginia	United States
14	Medizinische Universität Innsbruck	Innsbruck		Austria
15	Landeskrankenhaus Klagenfurt	Klagenfurt		Austria
16	Abt. Neurologie und Psychiatrie	Linz		Austria
17	LKH St. Pölten Department of Neurology	St. Pölten		Austria
18	Santa Casa de Misericordia de Belo Horizonte Departamento de Neurologia	Belo Horizonte		Brazil
19	Hospital de Clinicas de Porto Alegre	Porto Alegre		Brazil
20	Hospital Moinhos de Vento	Porto Alegre		Brazil
21	Hospital Mãe de Deus	Porto Alegre		Brazil
22	Santa Casa de Misericórdia de Porto Alegre Policlinica Santa Clara Sala de Neurologia	Porto Alegre		Brazil
23	Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto Unidade de Emergência Centro de Estudos	Ribeirão Preto		Brazil
24	UNIFESP	San Paulo		Brazil
25	Hospital São José de Joinville	Santa Catarina		Brazil
26	Hospital Santa Marcelina	Sao Paulo		Brazil
27	Hamilton Health Sciences Centre	Hamilton	Ontario	Canada
28	Grey Nun's Community Hospital	Edmonton		Canada
29	University of Alberta Hospital	Edmonton		Canada
30	Hamilton Health Sciences Centre	Hamilton		Canada
31	Kingston General Hospital	Kingston		Canada
32	Chinook Regional Hospital	Lethbridge		Canada
33	CHA- Hôpital de l'Enfant-Jésus	Quebec		Canada
34	University Hospital Brno	Brno		Czech Republic
35	University Hospital Hradec Kralove, Clinic of Neurology	Hradec Kralove		Czech Republic
36	Hospital Jihlava Clinic of Neurology	Jihlava		Czech Republic
37	Hospital Vítkovice Clinic of Neurology	Ostrava		Czech Republic
38	County Hospital Pardubice Clinic of Neurology	Pardubice		Czech Republic
39	Clinic of Neurology, Stroke Center, Charles University	Prague		Czech Republic
40	University Hospital Kralovske Vinohrady	Prague		Czech Republic
41	University Hospital Motol Clinic of Neurology	Prague		Czech Republic
42	CHU Jean Minjoz Besançon	Besancon		France
43	Hopital Pellegrin-Tripode	Bordeaux		France
44	CHU Henri Mondor	Créteil		France
45	Hopital Gui de Chauliac	Montpellier		France
46	Hôpital Bichat	Paris		France
47	Hôpital Lariboisière - Service Neurologie	Paris		France
48	Hôpital Saint Jean	Perpignan		France
49	Ärztlicher Direktor Neurologische Klinik, Neurologische Klink GmbH der Rhoen-Klinikum AG	Bad Neustadt / Saale		Germany
50	Marien-Krankenhaus gGmbH, Abteilung für Neurologie	Bergisch Gladbach		Germany
51	DRK Kliniken Berlin, Klinik fuer Neurologie	Berlin		Germany
52	Vivantes Klinikum Neukölln, Klinik für Neurologie, Stroke Unit	Berlin		Germany
53	Klinikum Bremen-Mitte	Bremen		Germany
54	Klinikum Bremerhaven-Reinkenheide gGmbH, Neurologische Klinik	Bremerhaven		Germany
55	Klinikum Chemnitz GmbH Chefarzt Klinik für Neurologie	Chemnitz		Germany
56	Helios Klinikum Erfurt GmbH	Erfurt		Germany
57	Universitätsklinikum Erlangen, Neurologische klinik	Erlangen		Germany
58	Universitätsklinikum Essen, Klinik und Poliklinik für Neurologie	Essen		Germany
59	Neurologische Universitätsklinik Freiburg, Neurozentrum	Freiburg		Germany	79106
60	Klinikum Fulda, Neurologische Klinik	Fulda		Germany
61	Evangelische Kliniken Gelsenkirchen GmbH Klinik für Neurologie und Klinische Neurophysiologie	Gelsenkirchen		Germany
62	Georg-August-Universitat Gottingen Neurologische Klinik	Gottingen		Germany
63	Ernst Moritz Arndt University	Grifswald		Germany
64	Askepios Klinik Altona	Hamburg		Germany
65	Askepios Klinik Heidberg	Hamburg		Germany
66	Klinikum Köln Merheim, Department of Neurology	Koln		Germany
67	Universitätsklinikum Leipzig AöR, Klinik und Poliklinik für Neurologie	Leipzig		Germany
68	Klinikum der Otto-von-Guericke-Universität Magdeburg, Neurologische Universitätsklinik	Magdeburg		Germany
69	Johannes Gutenberg Universitat, Klinik und Poliklinik fur Neurologie	Mainz		Germany
70	Klinikum 1 Minden, Neurologische Klinik	Minden		Germany
71	Universität Rostock Chefarzt Abteilung Neurologie	Rostock		Germany
72	ASKLEPIOS Fachklinikum Teupitz	Teupitz		Germany
73	Krankenhaus der Bramherzigen Brüder	Trier		Germany
74	Universitätsklinikum Ulm, Abteilung für Neurologie im RKU	Ulm		Germany
75	Heinrich Braun Klinikum Zwickau	Zwickau		Germany
76	Fővárosi Önkormányzat Péterfy Sándor utcai Kórház- Rendelőintézet és Baleseti Központ	Budapest		Hungary
77	Állami Egészségügyi Központ	Budapest		Hungary
78	Kenezy Korhaz Rendelointezet Egezsegugyi Szolgaltato Nonprofit Kft.	Debrecen		Hungary
79	University of Debrecen, Medical and Health Science Center	Debrecen		Hungary
80	Aladár Petz County Teaching Hospital	Gyor		Hungary
81	PM Flór Ferenc County Hospital	Kistarcsa		Hungary
82	Borsod-Abaúj-Zemplén County Hospital Miskolc	Miskolc		Hungary
83	Pécsi Tudományegyetem Klinikai Központ	Pecs		Hungary
84	Zala Megyei Kórház	Zalaegerszeg		Hungary
85	Bnai Zion Medical Center	Haifa		Israel
86	Neurological Dept. Edith Wolfson Medical Center	Holon		Israel	58100
87	Meir Medical Center	Kfar Saba		Israel
88	Sourasky Medical Center	Tel Aviv		Israel
89	Chaim Sheba Medical Center	Tel Hashomer		Israel
90	Ospedale Regionale Valle d'Aosta	Aosta		Italy
91	Dipartimento di Neuroscienze, Ospedale di Brotzu	Cagliari		Italy
92	Ospedale di Circolo di Varese	Lombardia		Italy
93	Istituto Scientifico San Raffaele - Stroke Unit	Milano		Italy
94	Istituto Neurologico C. Mondino	Pavia		Italy
95	Università di Perugia, Division of Internal and Cardiovascular Medicine - Stroke Unit	Perugia		Italy
96	Presidio Ospedaliero di Piacenza	Piacenza		Italy
97	Azienda Ospedaliera Sant'Andrea, Stroke Unit	Rome		Italy
98	Istituto Patologia Generale U.C.S.C	Rome		Italy
99	U.O.C. Stroke Unit	Rome		Italy
100	Università di Roma "La Sapienza" - Stroke Unit	Rome		Italy
101	Azienda Ospedaliera Universitaria "Santa Maria della Misericordia" Stroke Unit	Udine		Italy
102	Dong-A Medical Center	Busan		Korea, Republic of
103	Inje University BUSAN Paik Hospital	Busan		Korea, Republic of
104	Inje University ILSAN Paik Hospital	Goyang		Korea, Republic of
105	Chonnam National University Hospital	Gwangju		Korea, Republic of
106	Inha University Hospital	Incheon		Korea, Republic of
107	Seoul National University Bundang Hospital	Seongnam		Korea, Republic of
108	ASAN Medical Center	Seoul		Korea, Republic of
109	Severance Hospital	Seoul		Korea, Republic of
110	The Catholic University of Korea Seoul St. Mary's hospital	Seoul		Korea, Republic of
111	Catharina Ziekenhuis Neurologie	Eindhoven		Netherlands
112	Medisch Spectrum Twente Hoofd Afdeling Vasculaire Neurologie	Enschede		Netherlands
113	Atrium MC Parkstad	Heerlen		Netherlands
114	Isala Klinieken Ploikliniek Neurologie	Zwolle		Netherlands
115	Pomerania Traumatology Center, Regional Specialist Hospital im. Nicolaus Copernicus	Gdansk		Poland
116	Medical University of Lublin, Department of Neurology, Stroke Unit	Lublin		Poland
117	Samodzielny Publiczny Zespol Zakladow Opieki Zdrowotnej w Sandomierzu	Sandomierz		Poland
118	Szpital Powiatowy im. Marii Curie - Skłodowskiej w Skarżysku-Kamiennej	Skarżysko-Kamienna		Poland
119	Wojewodzki Szpital Specjalistyczny Nr 1 im. Prof. Jozefa Gasinskiego	Tychy		Poland
120	Instytut Psychiatrii i Neurologii Oddział Neurologiczny z Pododdziałem Udarowym	Warsaw		Poland
121	Medical University of Warsaw, Department of Neurology	Warsaw		Poland
122	Szpital Wolski im. dr Anny Gostyńskiej Samodzielny Publiczny Zakład Opieki Zdrowotnej, Oddział Neurologii	Warsaw		Poland
123	Wojskowy Instytut Medyczny, Oddział Neurologii	Warsaw		Poland
124	Hospital Professor Doutor Fernando Fonseca, EPE	Amadora		Portugal
125	Centro Hospitalar de Coimbra EPE	Coimbra		Portugal
126	Hospitais da Universidadde de Coimbra, EPE	Coimbra		Portugal
127	Centro de Estudos Egas Moniz - Hospital de Santa Maria	Lisboa		Portugal
128	Hospital de São Sebastião, EPE	Santa Maria da Feira		Portugal
129	Neurology Clinic, Faculty Hospital in Martin	Martin		Slovakia
130	University Hospital Nitra	Nitra		Slovakia
131	Hospital un Poliklinic	Spisska Nova Ves		Slovakia
132	Faculty Hospital Trnava	Trnava		Slovakia
133	Neurology dept.,Hospital Zilina	Zilina		Slovakia
134	Fichmed	Bloemfontein		South Africa
135	Constantiaberg Medi-clinic	Cape Town		South Africa
136	Union Hospital	Gauteng		South Africa
137	Helderberg Research Institute	Western Cape		South Africa
138	Triervlei Trial Centre	Western Cape		South Africa
139	Clinical Projects Research	Worcester		South Africa
140	Hospital Universitario de Albacete	Albacete		Spain
141	Hospital De La Santa Ta Creu i Sant Pau	Barcelona		Spain
142	Hospital del Mar	Barcelona		Spain
143	Hospital Germans Triasy Pujol	Barcelona		Spain
144	Hospital Vall D'hebron	Barcelona		Spain
145	Hospital Gregorio Maranon	Madrid		Spain
146	Hospital La Princesa	Madrid		Spain
147	Hospital Ramon y Cajal	Madrid		Spain
148	Hospital Universitario Clinico San Carlos	Madrid		Spain
149	Hospital Universitario La Paz	Madrid		Spain
150	Hospital Clinico Universitario de Santiago	Santiago de Compostela		Spain
151	Consorcio Hospital General Universitario Valencia	Valencia		Spain
152	Hospital Clinico Universitario De Valladolid	Valladolid		Spain
153	Universitätsspital Basel, Neurologie	Basel		Switzerland
154	Universitätsspital Zürich, Klinik für Neurologie	Zurich		Switzerland

Sponsors and Collaborators

D-Pharm Ltd.

Investigators

Principal Investigator: Ashfaq Shuaib, MD, University of Alberta Hospital, Edmonton, Canada
Principal Investigator: Vasco Salgado, MD, Hospital Professor Doutor Fernando Fonseca, EPE, Amadora, Portugal
Principal Investigator: Philippe Lyrer, Prof. Dr., Universitätsspital Basel, Neurologie, Basel, Switzerland
Principal Investigator: Tobien Schreuder, MD, Atrium MC Parkstad, Heerlen, Netherlands
Principal Investigator: Maria S Rocha, MD, Hospital Santa Marcelina, Sao Paulo, Brasil
Principal Investigator: Hugues Chabriat, Prof., Hôpital Lariboisière - Service Neurologie, Paris, France