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

October 23, 2012 updated by: D-Pharm Ltd.

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

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.

Study Overview

Status

Terminated

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

446

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Innsbruck, Austria
        • Medizinische Universitat Innsbruck
      • Klagenfurt, Austria
        • Landeskrankenhaus Klagenfurt
      • Linz, Austria
        • Abt. Neurologie und Psychiatrie
      • St. Pölten, Austria
        • LKH St. Pölten Department of Neurology
      • Belo Horizonte, Brazil
        • Santa Casa de Misericordia de Belo Horizonte Departamento de Neurologia
      • Porto Alegre, Brazil
        • Hospital de Clínicas de Porto Alegre
      • Porto Alegre, Brazil
        • Hospital Moinhos de Vento
      • Porto Alegre, Brazil
        • Hospital Mae de Deus
      • Porto Alegre, Brazil
        • Santa Casa de Misericórdia de Porto Alegre Policlinica Santa Clara Sala de Neurologia
      • Ribeirão Preto, Brazil
        • Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto Unidade de Emergência Centro de Estudos
      • San Paulo, Brazil
        • UNIFESP
      • Santa Catarina, Brazil
        • Hospital São José de Joinville
      • Sao Paulo, Brazil
        • Hospital Santa Marcelina
      • Edmonton, Canada
        • University of Alberta Hospital
      • Edmonton, Canada
        • Grey Nun's Community Hospital
      • Hamilton, Canada
        • Hamilton Health Sciences Centre
      • Kingston, Canada
        • Kingston General Hospital
      • Lethbridge, Canada
        • Chinook Regional Hospital
      • Quebec, Canada
        • CHA- Hôpital de l'Enfant-Jésus
    • Ontario
      • Hamilton, Ontario, Canada
        • Hamilton Health Sciences Centre
      • Brno, Czech Republic
        • University Hospital Brno
      • Hradec Kralove, Czech Republic
        • University Hospital Hradec Kralove, Clinic of Neurology
      • Jihlava, Czech Republic
        • Hospital Jihlava Clinic of Neurology
      • Ostrava, Czech Republic
        • Hospital Vítkovice Clinic of Neurology
      • Pardubice, Czech Republic
        • County Hospital Pardubice Clinic of Neurology
      • Prague, Czech Republic
        • University Hospital Kralovske Vinohrady
      • Prague, Czech Republic
        • Clinic of Neurology, Stroke Center, Charles University
      • Prague, Czech Republic
        • University Hospital Motol Clinic of Neurology
      • Besancon, France
        • Chu Jean Minjoz Besancon
      • Bordeaux, France
        • Hopital Pellegrin-Tripode
      • Créteil, France
        • CHU Henri Mondor
      • Montpellier, France
        • Hopital Gui de Chauliac
      • Paris, France
        • Hôpital Bichat
      • Paris, France
        • Hôpital Lariboisière - Service Neurologie
      • Perpignan, France
        • Hopital Saint Jean
      • Bad Neustadt / Saale, Germany
        • Ärztlicher Direktor Neurologische Klinik, Neurologische Klink GmbH der Rhoen-Klinikum AG
      • Bergisch Gladbach, Germany
        • Marien-Krankenhaus gGmbH, Abteilung für Neurologie
      • Berlin, Germany
        • DRK Kliniken Berlin, Klinik fuer Neurologie
      • Berlin, Germany
        • Vivantes Klinikum Neukölln, Klinik für Neurologie, Stroke Unit
      • Bremen, Germany
        • Klinikum Bremen-Mitte
      • Bremerhaven, Germany
        • Klinikum Bremerhaven-Reinkenheide gGmbH, Neurologische Klinik
      • Chemnitz, Germany
        • Klinikum Chemnitz GmbH Chefarzt Klinik für Neurologie
      • Erfurt, Germany
        • HELIOS Klinikum Erfurt GmbH
      • Erlangen, Germany
        • Universitätsklinikum Erlangen, Neurologische Klinik
      • Essen, Germany
        • Universitätsklinikum Essen, Klinik und Poliklinik für Neurologie
      • Freiburg, Germany, 79106
        • Neurologische Universitätsklinik Freiburg, Neurozentrum
      • Fulda, Germany
        • Klinikum Fulda, Neurologische Klinik
      • Gelsenkirchen, Germany
        • Evangelische Kliniken Gelsenkirchen GmbH Klinik für Neurologie und Klinische Neurophysiologie
      • Gottingen, Germany
        • Georg-August-Universitat Gottingen Neurologische Klinik
      • Grifswald, Germany
        • Ernst Moritz Arndt University
      • Hamburg, Germany
        • Askepios Klinik Altona
      • Hamburg, Germany
        • Askepios Klinik Heidberg
      • Koln, Germany
        • Klinikum Köln Merheim, Department of Neurology
      • Leipzig, Germany
        • Universitätsklinikum Leipzig AöR, Klinik und Poliklinik für Neurologie
      • Magdeburg, Germany
        • Klinikum der Otto-von-Guericke-Universität Magdeburg, Neurologische Universitätsklinik
      • Mainz, Germany
        • Johannes Gutenberg Universitat, Klinik und Poliklinik fur Neurologie
      • Minden, Germany
        • Klinikum 1 Minden, Neurologische Klinik
      • Rostock, Germany
        • Universität Rostock Chefarzt Abteilung Neurologie
      • Teupitz, Germany
        • ASKLEPIOS Fachklinikum Teupitz
      • Trier, Germany
        • Krankenhaus der Bramherzigen Brüder
      • Ulm, Germany
        • Universitätsklinikum Ulm, Abteilung für Neurologie im RKU
      • Zwickau, Germany
        • Heinrich Braun Klinikum Zwickau
      • Budapest, Hungary
        • Fővárosi Önkormányzat Péterfy Sándor utcai Kórház- Rendelőintézet és Baleseti Központ
      • Budapest, Hungary
        • Állami Egészségügyi Központ
      • Debrecen, Hungary
        • University of Debrecen, Medical and Health Science Center
      • Debrecen, Hungary
        • Kenezy Korhaz Rendelointezet Egezsegugyi Szolgaltato Nonprofit Kft.
      • Gyor, Hungary
        • Aladár Petz County Teaching Hospital
      • Kistarcsa, Hungary
        • PM Flór Ferenc County Hospital
      • Miskolc, Hungary
        • Borsod-Abaúj-Zemplén County Hospital Miskolc
      • Pecs, Hungary
        • Pecsi Tudomanyegyetem Klinikai Kozpont
      • Zalaegerszeg, Hungary
        • Zala Megyei Kórház
      • Haifa, Israel
        • Bnai Zion Medical Center
      • Holon, Israel, 58100
        • Neurological Dept. Edith Wolfson Medical Center
      • Kfar Saba, Israel
        • Meir Medical Center
      • Tel Aviv, Israel
        • Sourasky Medical Center
      • Tel Hashomer, Israel
        • Chaim Sheba Medical Center
      • Aosta, Italy
        • Ospedale Regionale Valle d'Aosta
      • Cagliari, Italy
        • Dipartimento di Neuroscienze, Ospedale di Brotzu
      • Lombardia, Italy
        • Ospedale di Circolo di Varese
      • Milano, Italy
        • Istituto Scientifico San Raffaele - Stroke Unit
      • Pavia, Italy
        • Istituto Neurologico C. Mondino
      • Perugia, Italy
        • Università di Perugia, Division of Internal and Cardiovascular Medicine - Stroke Unit
      • Piacenza, Italy
        • Presidio Ospedaliero di Piacenza
      • Rome, Italy
        • Azienda Ospedaliera Sant'Andrea, Stroke Unit
      • Rome, Italy
        • Istituto Patologia Generale U.C.S.C
      • Rome, Italy
        • U.O.C. Stroke Unit
      • Rome, Italy
        • Università di Roma "La Sapienza" - Stroke Unit
      • Udine, Italy
        • Azienda Ospedaliera Universitaria "Santa Maria della Misericordia" Stroke Unit
      • Busan, Korea, Republic of
        • Inje University Busan Paik Hospital
      • Busan, Korea, Republic of
        • Dong-A Medical Center
      • Goyang, Korea, Republic of
        • Inje University Ilsan Paik Hospital
      • Gwangju, Korea, Republic of
        • Chonnam National University Hospital
      • Incheon, Korea, Republic of
        • Inha University Hospital
      • Seongnam, Korea, Republic of
        • Seoul National University Bundang Hospital
      • Seoul, Korea, Republic of
        • Asan Medical Center
      • Seoul, Korea, Republic of
        • The Catholic University of Korea Seoul St. Mary's Hospital
      • Seoul, Korea, Republic of
        • Severance Hospital
      • Eindhoven, Netherlands
        • Catharina Ziekenhuis Neurologie
      • Enschede, Netherlands
        • Medisch Spectrum Twente Hoofd Afdeling Vasculaire Neurologie
      • Heerlen, Netherlands
        • Atrium MC Parkstad
      • Zwolle, Netherlands
        • Isala Klinieken Ploikliniek Neurologie
      • Gdansk, Poland
        • Pomerania Traumatology Center, Regional Specialist Hospital im. Nicolaus Copernicus
      • Lublin, Poland
        • Medical University of Lublin, Department of Neurology, Stroke Unit
      • Sandomierz, Poland
        • Samodzielny Publiczny Zespol Zakladow Opieki Zdrowotnej w Sandomierzu
      • Skarżysko-Kamienna, Poland
        • Szpital Powiatowy im. Marii Curie - Skłodowskiej w Skarżysku-Kamiennej
      • Tychy, Poland
        • Wojewodzki Szpital Specjalistyczny Nr 1 im. Prof. Jozefa Gasinskiego
      • Warsaw, Poland
        • Instytut Psychiatrii i Neurologii Oddział Neurologiczny z Pododdziałem Udarowym
      • Warsaw, Poland
        • Medical University of Warsaw, Department of Neurology
      • Warsaw, Poland
        • Szpital Wolski im. dr Anny Gostyńskiej Samodzielny Publiczny Zakład Opieki Zdrowotnej, Oddział Neurologii
      • Warsaw, Poland
        • Wojskowy Instytut Medyczny, Oddział Neurologii
      • Amadora, Portugal
        • Hospital Professor Doutor Fernando Fonseca, EPE
      • Coimbra, Portugal
        • Centro Hospitalar de Coimbra EPE
      • Coimbra, Portugal
        • Hospitais da Universidadde de Coimbra, EPE
      • Lisboa, Portugal
        • Centro de Estudos Egas Moniz - Hospital de Santa Maria
      • Santa Maria da Feira, Portugal
        • Hospital de São Sebastião, EPE
      • Martin, Slovakia
        • Neurology Clinic, Faculty Hospital in Martin
      • Nitra, Slovakia
        • University Hospital Nitra
      • Spisska Nova Ves, Slovakia
        • Hospital un Poliklinic
      • Trnava, Slovakia
        • Faculty Hospital Trnava
      • Zilina, Slovakia
        • Neurology dept.,Hospital Zilina
      • Bloemfontein, South Africa
        • Fichmed
      • Cape Town, South Africa
        • Constantiaberg Medi-clinic
      • Gauteng, South Africa
        • Union Hospital
      • Western Cape, South Africa
        • Helderberg Research Institute
      • Western Cape, South Africa
        • Triervlei Trial Centre
      • Worcester, South Africa
        • Clinical Projects Research
      • Albacete, Spain
        • Hospital Universitario de Albacete
      • Barcelona, Spain
        • Hospital del Mar
      • Barcelona, Spain
        • Hospital Vall d'Hebron
      • Barcelona, Spain
        • Hospital De La Santa Ta Creu i Sant Pau
      • Barcelona, Spain
        • Hospital Germans Triasy Pujol
      • Madrid, Spain
        • Hospital Ramon y Cajal
      • Madrid, Spain
        • Hospital Gregorio Marañón
      • Madrid, Spain
        • Hospital Universitario Clinico San Carlos
      • Madrid, Spain
        • Hospital Universitario La Paz
      • Madrid, Spain
        • Hospital La Princesa
      • Santiago de Compostela, Spain
        • Hospital Clinico Universitario de Santiago
      • Valencia, Spain
        • Consorcio Hospital General Universitario Valencia
      • Valladolid, Spain
        • Hospital Clinico Universitario de Valladolid
      • Basel, Switzerland
        • Universitätsspital Basel, Neurologie
      • Zurich, Switzerland
        • Universitätsspital Zürich, Klinik für Neurologie
    • California
      • Oceanside, California, United States
        • Research Center of Southern California
    • Connecticut
      • Danbury, Connecticut, United States
        • Associated Neurologists, P.C.
    • Georgia
      • Savannah, Georgia, United States
        • Memorial Health University Medical Center
    • Kentucky
      • Lexington, Kentucky, United States
        • The University of Kentucky The Methodist Hospital
      • Louisville, Kentucky, United States
        • University of Louisville, Kentucky Neuroscience Research
    • Massachusetts
      • Boston, Massachusetts, United States
        • Tufts Medical Center
    • New Jersey
      • Trenton, New Jersey, United States
        • Capital Health Regional Medical Center Neuroscience Institute
    • North Carolina
      • Charlotte, North Carolina, United States
        • Presbitarian Hospital
    • Ohio
      • Youngstown, Ohio, United States
        • St. Elizabeth's Medical Center
    • Oregon
      • Tualatin, Oregon, United States
        • Legacy Meridian Park Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
        • Thomas Jefferson University
    • Texas
      • Houston, Texas, United States
        • The Methodist Hospital
    • Virginia
      • Roanoke, Virginia, United States
        • Carilion Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  1. M or F age 18 - 85, inclusive
  2. 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)
  3. 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.
  4. Screening NIHSS score of 10 to 16, inclusive
  5. Readily accessible peripheral venous access for clinical trial material (CTM) administration and blood sampling
  6. 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.
  7. 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:

  1. An intracerebral or subarachnoid hemorrhage per screening/baseline computerized tomography scan or susceptibility-weighted magnetic resonance imaging
  2. A candidate for either:

    1. thrombolytic therapy, or have been treated with thrombolytic therapy for the current stroke
    2. mechanical thromboembolectomy, or have been treated with mechanical thromboembolectomy for the current stroke
  3. 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
  4. Have seizure(s) anytime from stroke onset to screening/baseline NIHSS evaluation
  5. 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
  6. Likely to undergo a procedure involving cardiopulmonary bypass during the study period
  7. Suffered a myocardial infarction in the last 90 days
  8. 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)
  9. Rapid spontaneous improvement of neurological signs during screening/baseline assessments
  10. Premorbid neurological deficits and functional limitations assessed by a pre-stroke Modified Rankin Scale score of > 1
  11. 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
  12. Either severe hypertension or hypotension, as measured by at least 2 consecutive supine measurements taken 10 minutes apart prior to randomization.
  13. 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.
  14. Have a platelet count of <100,000/mm3 or, for patients on oral anticoagulants at study entry, INR of >4
  15. 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
  16. Positive urine pregnancy test at screening/baseline or be a lactating female
  17. Currently dependent on, or abusing, alcohol or one or more of the following: sympathomimetic amines, cannabis, cocaine, hallucinogens, inhalants, opioids, phencyclidine, sedatives and hypnotics
  18. 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
  19. Severe anemia as measured by a hemoglobin value of < 7 g/dl.
  20. In a dependent relationship with the physician or the study sponsor.
  21. Known hypersensitivity to any component of the investigational product.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Modified Rankin Scale (mRS) categorical analysis ("shift")
Time Frame: 90 days
90 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recovery, defined as a score of ≤ 1 on modified Rankin Score
Time Frame: 90 days
90 days
Safety and tolerability
Time Frame: 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)
throughout study - baseline until day 90
recovery as assessed by an NIHSS of not more than 1
Time Frame: 90 days
90 days
'home time'
Time Frame: 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
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2009

Primary Completion (Actual)

April 1, 2012

Study Completion (Actual)

April 1, 2012

Study Registration Dates

First Submitted

May 4, 2009

First Submitted That Met QC Criteria

May 5, 2009

First Posted (Estimate)

May 6, 2009

Study Record Updates

Last Update Posted (Estimate)

October 24, 2012

Last Update Submitted That Met QC Criteria

October 23, 2012

Last Verified

October 1, 2012

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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