Acute Ischemic StrokePhase 3MACSINCT00893867
Efficacy and Safety Study of DP-b99 in Treating Acute Ischemic Stroke
A Phase 3 study testing DP-b99 in people with Acute Ischemic Stroke, run by D-Pharm Ltd. at 154 sites in 18 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Acute Ischemic Stroke
- What is being tested?
- DP-b99
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 446 participants
- Where
- 154 sitesin 18 countries
- Study dates
- Dec 2009to Apr 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 10Show fewer
- 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
Who cannot join
- 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
Show all 23Show fewer
- 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.
Trial locations and contacts
154 sites in 18 countries.
154 sites in 18 countries
Germany27 sites
Ärztlicher Direktor Neurologische Klinik, Neurologische Klink GmbH der Rhoen-Klinikum AG
Bad Neustadt / Saale
Marien-Krankenhaus gGmbH, Abteilung für Neurologie
Bergisch Gladbach
DRK Kliniken Berlin, Klinik fuer Neurologie
Berlin
Vivantes Klinikum Neukölln, Klinik für Neurologie, Stroke Unit
Berlin
Klinikum Bremen-Mitte
Bremen
Klinikum Bremerhaven-Reinkenheide gGmbH, Neurologische Klinik
Bremerhaven
Klinikum Chemnitz GmbH Chefarzt Klinik für Neurologie
Chemnitz
Klinikum Köln Merheim, Department of Neurology
Cologne
Helios Klinikum Erfurt GmbH
Erfurt
Universitätsklinikum Erlangen, Neurologische klinik
Erlangen
Universitätsklinikum Essen, Klinik und Poliklinik für Neurologie
Essen
Neurologische Universitätsklinik Freiburg, Neurozentrum
Freiburg im Breisgau, 79106
Klinikum Fulda, Neurologische Klinik
Fulda
Evangelische Kliniken Gelsenkirchen GmbH Klinik für Neurologie und Klinische Neurophysiologie
Gelsenkirchen
Georg-August-Universitat Gottingen Neurologische Klinik
Göttingen
Ernst Moritz Arndt University
Grifswald
Askepios Klinik Altona
Hamburg
Askepios Klinik Heidberg
Hamburg
Universitätsklinikum Leipzig AöR, Klinik und Poliklinik für Neurologie
Leipzig
Klinikum der Otto-von-Guericke-Universität Magdeburg, Neurologische Universitätsklinik
Magdeburg
Johannes Gutenberg Universitat, Klinik und Poliklinik fur Neurologie
Mainz
Klinikum 1 Minden, Neurologische Klinik
Minden
Universität Rostock Chefarzt Abteilung Neurologie
Rostock
ASKLEPIOS Fachklinikum Teupitz
Teupitz
Krankenhaus der Bramherzigen Brüder
Trier
Universitätsklinikum Ulm, Abteilung für Neurologie im RKU
Ulm
Heinrich Braun Klinikum Zwickau
Zwickau
United States13 sites
Tufts Medical Center
Boston, Massachusetts
Presbitarian Hospital
Charlotte, North Carolina
Associated Neurologists, P.C.
Danbury, Connecticut
The Methodist Hospital
Houston, Texas
The University of Kentucky The Methodist Hospital
Lexington, Kentucky
University of Louisville, Kentucky Neuroscience Research
Louisville, Kentucky
Research Center of Southern California
Oceanside, California
Thomas Jefferson University
Philadelphia, Pennsylvania
Carilion Clinic
Roanoke, Virginia
Memorial Health University Medical Center
Savannah, Georgia
Capital Health Regional Medical Center Neuroscience Institute
Trenton, New Jersey
Legacy Meridian Park Medical Center
Tualatin, Oregon
St. Elizabeth's Medical Center
Youngstown, Ohio
Spain13 sites
Hospital Universitario de Albacete
Albacete
Hospital De La Santa Ta Creu i Sant Pau
Barcelona
Hospital del Mar
Barcelona
Hospital Germans Triasy Pujol
Barcelona
Hospital Vall D'hebron
Barcelona
Hospital Gregorio Maranon
Madrid
Hospital La Princesa
Madrid
Hospital Ramon y Cajal
Madrid
Hospital Universitario Clinico San Carlos
Madrid
Hospital Universitario La Paz
Madrid
Hospital Clinico Universitario de Santiago
Santiago de Compostela
Consorcio Hospital General Universitario Valencia
Valencia
Hospital Clinico Universitario De Valladolid
Valladolid
Italy12 sites
Ospedale Regionale Valle d'Aosta
Aosta
Dipartimento di Neuroscienze, Ospedale di Brotzu
Cagliari
Ospedale di Circolo di Varese
Lombardia
Istituto Scientifico San Raffaele - Stroke Unit
Milan
Istituto Neurologico C. Mondino
Pavia
Università di Perugia, Division of Internal and Cardiovascular Medicine - Stroke Unit
Perugia
Presidio Ospedaliero di Piacenza
Piacenza
Azienda Ospedaliera Sant'Andrea, Stroke Unit
Rome
Istituto Patologia Generale U.C.S.C
Rome
U.O.C. Stroke Unit
Rome
Università di Roma "La Sapienza" - Stroke Unit
Rome
Azienda Ospedaliera Universitaria "Santa Maria della Misericordia" Stroke Unit
Udine
Brazil9 sites
Santa Casa de Misericordia de Belo Horizonte Departamento de Neurologia
Belo Horizonte
Hospital de Clinicas de Porto Alegre
Porto Alegre
Hospital Moinhos de Vento
Porto Alegre
Hospital Mãe de Deus
Porto Alegre
Santa Casa de Misericórdia de Porto Alegre Policlinica Santa Clara Sala de Neurologia
Porto Alegre
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto Unidade de Emergência Centro de Estudos
Ribeirão Preto
Hospital São José de Joinville
Santa Catarina
Hospital Santa Marcelina
São Paulo
UNIFESP
São Paulo
Hungary9 sites
Fővárosi Önkormányzat Péterfy Sándor utcai Kórház- Rendelőintézet és Baleseti Központ
Budapest
Állami Egészségügyi Központ
Budapest
Kenezy Korhaz Rendelointezet Egezsegugyi Szolgaltato Nonprofit Kft.
Debrecen
University of Debrecen, Medical and Health Science Center
Debrecen
Aladár Petz County Teaching Hospital
Győr
PM Flór Ferenc County Hospital
Kistarcsa
Borsod-Abaúj-Zemplén County Hospital Miskolc
Miskolc
Pécsi Tudományegyetem Klinikai Központ
Pécs
Zala Megyei Kórház
Zalaegerszeg
Poland9 sites
Pomerania Traumatology Center, Regional Specialist Hospital im. Nicolaus Copernicus
Gdansk
Medical University of Lublin, Department of Neurology, Stroke Unit
Lublin
Samodzielny Publiczny Zespol Zakladow Opieki Zdrowotnej w Sandomierzu
Sandomierz
Szpital Powiatowy im. Marii Curie - Skłodowskiej w Skarżysku-Kamiennej
Skarżysko-Kamienna
Wojewodzki Szpital Specjalistyczny Nr 1 im. Prof. Jozefa Gasinskiego
Tychy
Instytut Psychiatrii i Neurologii Oddział Neurologiczny z Pododdziałem Udarowym
Warsaw
Medical University of Warsaw, Department of Neurology
Warsaw
Szpital Wolski im. dr Anny Gostyńskiej Samodzielny Publiczny Zakład Opieki Zdrowotnej, Oddział Neurologii
Warsaw
Wojskowy Instytut Medyczny, Oddział Neurologii
Warsaw
South Korea9 sites
Dong-A Medical Center
Busan
Inje University BUSAN Paik Hospital
Busan
Inje University ILSAN Paik Hospital
Goyang
Chonnam National University Hospital
Gwangju
Inha University Hospital
Incheon
Seoul National University Bundang Hospital
Seongnam
ASAN Medical Center
Seoul
Severance Hospital
Seoul
The Catholic University of Korea Seoul St. Mary's hospital
Seoul
Czechia8 sites
University Hospital Brno
Brno
University Hospital Hradec Kralove, Clinic of Neurology
Hradec Králové
Hospital Jihlava Clinic of Neurology
Jihlava
Hospital Vítkovice Clinic of Neurology
Ostrava
County Hospital Pardubice Clinic of Neurology
Pardubice
Clinic of Neurology, Stroke Center, Charles University
Prague
University Hospital Kralovske Vinohrady
Prague
University Hospital Motol Clinic of Neurology
Prague
Canada7 sites
Grey Nun's Community Hospital
Edmonton
University of Alberta Hospital
Edmonton
Hamilton Health Sciences Centre
Hamilton, Ontario
Hamilton Health Sciences Centre
Hamilton
Kingston General Hospital
Kingston
Chinook Regional Hospital
Lethbridge
CHA- Hôpital de l'Enfant-Jésus
Québec
France7 sites
CHU Jean Minjoz Besançon
Besançon
Hopital Pellegrin-Tripode
Bordeaux
CHU Henri Mondor
Créteil
Hopital Gui de Chauliac
Montpellier
Hôpital Bichat
Paris
Hôpital Lariboisière - Service Neurologie
Paris
Hôpital Saint Jean
Perpignan
South Africa6 sites
Fichmed
Bloemfontein
Constantiaberg Medi-clinic
Cape Town
Union Hospital
Gauteng
Helderberg Research Institute
Western Cape
Triervlei Trial Centre
Western Cape
Clinical Projects Research
Worcester
Israel5 sites
Bnai Zion Medical Center
Haifa
Neurological Dept. Edith Wolfson Medical Center
Holon, 58100
Meir Medical Center
Kfar Saba
Sourasky Medical Center
Tel Aviv
Chaim Sheba Medical Center
Tel HaShomer
Portugal5 sites
Hospital Professor Doutor Fernando Fonseca, EPE
Amadora
Centro Hospitalar de Coimbra EPE
Coimbra
Hospitais da Universidadde de Coimbra, EPE
Coimbra
Centro de Estudos Egas Moniz - Hospital de Santa Maria
Lisbon
Hospital de São Sebastião, EPE
Santa Maria da Feira
Slovakia5 sites
Neurology Clinic, Faculty Hospital in Martin
Martin
University Hospital Nitra
Nitra
Hospital un Poliklinic
Spišská Nová Ves
Faculty Hospital Trnava
Trnava
Neurology dept.,Hospital Zilina
Žilina
Austria4 sites
Medizinische Universität Innsbruck
Innsbruck
Landeskrankenhaus Klagenfurt
Klagenfurt
Abt. Neurologie und Psychiatrie
Linz
LKH St. Pölten Department of Neurology
Sankt Pölten
Netherlands4 sites
Catharina Ziekenhuis Neurologie
Eindhoven
Medisch Spectrum Twente Hoofd Afdeling Vasculaire Neurologie
Enschede
Atrium MC Parkstad
Heerlen
Isala Klinieken Ploikliniek Neurologie
Zwolle
Switzerland2 sites
Universitätsspital Basel, Neurologie
Basel
Universitätsspital Zürich, Klinik für Neurologie
Zurich
About this study
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
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.
Read the 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.
- Conditions
- Acute Ischemic Stroke
- Being tested
- DP-b99, Placebo
- Keywords
- acute ischemic stroke, neuroprotective agent
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DP-b99Drug
1mg/kg/day over 4 consecutive days given intravenously and initiated up to 9 hours following acute stroke onset.
PlaceboDrug
1mg/kg/day over 4 consecutive days given intravenously and initiated up to 9 hours following acute stroke onset.
| Study group | Role | What they receive |
|---|---|---|
| DP-b99 | Experimental | Not described Receives: Drug: DP-b99 |
| Mannitol | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modified Rankin Scale (mRS) categorical analysis ("shift")
Measured: 90 days
Secondary outcomes (4)
Recovery, defined as a score of ≤ 1 on modified Rankin Score
Measured: 90 days
Safety and tolerability
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)
Measured: throughout study - baseline until day 90
recovery as assessed by an NIHSS of not more than 1
Measured: 90 days
'home time'
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
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2009 (estimated)
- Study startDec 2009
- Primary completionApr 2012
- Study completionApr 2012
Why it stopped: The result of a pre-planned interim futility analysis
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Acute Ischemic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 446 participants (actual)
Sponsor and investigators
- Lead sponsor
- D-Pharm Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ashfaq Shuaib, MD, Principal investigator, University of Alberta Hospital, Edmonton, CanadaVasco Salgado, MD, Principal investigator, Hospital Professor Doutor Fernando Fonseca, EPE, Amadora, PortugalPhilippe Lyrer, Prof. Dr., Principal investigator, Universitätsspital Basel, Neurologie, Basel, SwitzerlandTobien Schreuder, MD, Principal investigator, Atrium MC Parkstad, Heerlen, NetherlandsMaria S Rocha, MD, Principal investigator, Hospital Santa Marcelina, Sao Paulo, BrasilHugues Chabriat, Prof., Principal investigator, Hôpital Lariboisière - Service Neurologie, Paris, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00893867
- Sponsor's protocol ID
- Ptcl-01373
- Acronym
- MACSI
- Status last verified
- Oct 2012
- First submitted
- 4 May 2009
- Last updated
- 24 Oct 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Diener HC, Schneider D, Lampl Y, Bornstein NM, Kozak A, Rosenberg G. DP-b99, a membrane-activated metal ion chelator, as neuroprotective therapy in ischemic stroke. Stroke. 2008 Jun;39(6):1774-8. doi: 10.1161/STROKEAHA.107.506378. Epub 2008 Apr 10.
PubMed 18403736Rosenberg G, Angel I, Kozak A. Clinical pharmacology of DP-b99 in healthy volunteers: first administration to humans. Br J Clin Pharmacol. 2005 Jul;60(1):7-16. doi: 10.1111/j.1365-2125.2005.02378.x.
PubMed 15963088Barkalifa R, Hershfinkel M, Friedman JE, Kozak A, Sekler I. The lipophilic zinc chelator DP-b99 prevents zinc induced neuronal death. Eur J Pharmacol. 2009 Sep 15;618(1-3):15-21. doi: 10.1016/j.ejphar.2009.07.019. Epub 2009 Jul 19.
PubMed 19622352Rosenberg G, Bornstein N, Diener HC, Gorelick PB, Shuaib A, Lees K; MACSI investigators. The Membrane-Activated Chelator Stroke Intervention (MACSI) Trial of DP-b99 in acute ischemic stroke: a randomized, double-blind, placebo-controlled, multinational pivotal phase III study. Int J Stroke. 2011 Aug;6(4):362-7. doi: 10.1111/j.1747-4949.2011.00608.x. Epub 2011 Jun 6.
PubMed 21645269Rosenberg G, Marshall LS, Caraco Y. The neuroprotective agent DP-b99 does not interact with s-warfarin in vivo despite significant CYP2C9 inhibition in vitro. Basic Clin Pharmacol Toxicol. 2011 Apr;108(4):289-92. doi: 10.1111/j.1742-7843.2010.00654.x. Epub 2010 Dec 16. No abstract available.
PubMed 21414144
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00893867
- Acronym / sponsor ID
- MACSI / Ptcl-01373
- Conditions
- Acute Ischemic Stroke
- Keywords
- acute ischemic stroke, neuroprotective agent
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The result of a pre-planned interim futility analysis
- Enrolment
- 446 participants (actual)
- Lead sponsor
- D-Pharm Ltd.Industry (pharma, biotech, devices)
- Study start
- Dec 2009
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 6 May 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DP-b99 | Experimental | Drug: DP-b99 |
| Mannitol | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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):
- 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
Key exclusion criteria (23 listed)
- An intracerebral or subarachnoid hemorrhage per screening/baseline computerized tomography scan or susceptibility-weighted magnetic resonance imaging
- A candidate for either:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DP-b991mg/kg/day over 4 consecutive days given intravenously and initiated up to 9 hours following acute stroke onset. | Drug | DP-b99 |
| Placebo1mg/kg/day over 4 consecutive days given intravenously and initiated up to 9 hours following acute stroke onset. | Drug | Mannitol |
Primary outcome
Modified Rankin Scale (mRS) categorical analysis ("shift")
Time frame: 90 days
4 secondary outcomes
Recovery, defined as a score of ≤ 1 on modified Rankin Score
Time frame: 90 days
Safety and tolerability
Time frame: throughout study - baseline until day 90
recovery as assessed by an NIHSS of not more than 1
Time frame: 90 days
'home time'
Time frame: 90 days
Results and safety
The study was stopped early (reason given: The result of a pre-planned interim futility analysis). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2012.
- Background: PubMed 18403736Diener HC, Schneider D, Lampl Y, Bornstein NM, Kozak A, Rosenberg G. DP-b99, a membrane-activated metal ion chelator, as neuroprotective therapy in ischemic stroke. Stroke. 2008 Jun;39(6):1774-8. doi: 10.1161/STROKEAHA.107.506378. Epub 2008 Apr 10.
- Background: PubMed 15963088Rosenberg G, Angel I, Kozak A. Clinical pharmacology of DP-b99 in healthy volunteers: first administration to humans. Br J Clin Pharmacol. 2005 Jul;60(1):7-16. doi: 10.1111/j.1365-2125.2005.02378.x.
- Background: PubMed 19622352Barkalifa R, Hershfinkel M, Friedman JE, Kozak A, Sekler I. The lipophilic zinc chelator DP-b99 prevents zinc induced neuronal death. Eur J Pharmacol. 2009 Sep 15;618(1-3):15-21. doi: 10.1016/j.ejphar.2009.07.019. Epub 2009 Jul 19.
- Background: PubMed 21645269Rosenberg G, Bornstein N, Diener HC, Gorelick PB, Shuaib A, Lees K; MACSI investigators. The Membrane-Activated Chelator Stroke Intervention (MACSI) Trial of DP-b99 in acute ischemic stroke: a randomized, double-blind, placebo-controlled, multinational pivotal phase III study. Int J Stroke. 2011 Aug;6(4):362-7. doi: 10.1111/j.1747-4949.2011.00608.x. Epub 2011 Jun 6.
- Background: PubMed 21414144Rosenberg G, Marshall LS, Caraco Y. The neuroprotective agent DP-b99 does not interact with s-warfarin in vivo despite significant CYP2C9 inhibition in vitro. Basic Clin Pharmacol Toxicol. 2011 Apr;108(4):289-92. doi: 10.1111/j.1742-7843.2010.00654.x. Epub 2010 Dec 16. No abstract available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ashfaq Shuaib, MD principal investigator
University of Alberta Hospital, Edmonton, Canada
Vasco Salgado, MD principal investigator
Hospital Professor Doutor Fernando Fonseca, EPE, Amadora, Portugal
Philippe Lyrer, Prof. Dr. principal investigator
Universitätsspital Basel, Neurologie, Basel, Switzerland
154 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing DP-b99 in people with Acute Ischemic Stroke, run by D-Pharm Ltd. at 154 sites in 18 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 154 sites in Germany, United States, Spain, Italy, Brazil and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The result of a pre-planned interim futility analysis). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Modified Rankin Scale (mRS) categorical analysis ("shift") (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00893867, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2012.