StrokePhase 3NCT00167765
Abciximab in Wake-up Stroke
A Phase 3 study testing Abciximab in people with Stroke, run by University of Zurich at 2 sites in 2 countries.
Trial summary
The purpose of the prospective, randomized, double blind, placebo-controlled multicenter pilot study is to evaluate the effectiveness of abciximab on rescuing the hypoperfused brain tissue, as assessed by MRI, and the relative safety of abciximab in patients with wake-up stroke. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke
- What is being tested?
- Abciximab
- How many people
- 50 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Mar 2005to May 2005
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient who awakes with an acute ischemic stroke in the anterior circulation.
- Planned start of study agent >3 hours and £6 hours from time of awakening and <1 hour after MRI mismatch diagnosis is established (cf. item 5 below).
- Pre-randomization NIHSS score of 4-20.
- Age >18 years.
- MRI showing a PWI-DWI mismatch defined by visual estimation, where the PWI lesion will be >130% of the DWI volume.
- Written informed consent, signed and dated by the subject (or subject's authorized representative, if allowed by local laws) and by the person obtaining the consent, indicating agreement to comply with all protocol-specified procedures.
Who cannot join
- General:
- Participation in another study with an investigational drug or device within the last 30 days.
- Prior participation in the present study, or planned participation in another trial.
- Symptoms suggestive of subarachnoid hemorrhage, even if MRI/CT scan is negative for hemorrhage.
- Women known to be pregnant, lactating, or having a positive or indeterminate pregnancy test.
- Stroke Related
Show all 43Show fewer
- Stupor or coma (NIHSS level of consciousness score ≥2 {item 1a}).
- High clinical suspicion of septic embolus.
- Rapidly improving symptoms.
- Thrombosis involving the cerebral veins.
- Brain Imaging Related
- Evidence of ICH by T2* MRI and/or noncontrast enhanced head CT.
- MRI and/or CT evidence of nonvascular cause for the neurological symptoms.
- DWI infarct size >50% of the MCA territory.
- Signs of mass effect causing shift of midline structures on CT scan.
- Contraindication to undergo MR imaging (eg pacemaker).
- Suspicion of occlusion of the ipsilateral ICA at MRA.
- Safety Related
- Persistent hypertension with systolic blood pressure (SBP) >185 mm Hg or diastolic blood pressure (DBP) >110 mm Hg (mean of 3 consecutive arm cuff readings over 20-30 minutes), not controlled by antihypertensive therapy or requiring nitroprusside for control.
- Anticipated need for major surgery within 72 hours after randomization (eg, carotid endarterectomy, hip fracture repair).
- Any intracranial surgery, serious head trauma (any head injury that required hospitalization), or stroke within the past 3 months.
- History of ICH at any time in the past.
- Major trauma at the time of stroke (eg, hip fracture).
- Presence or history of intracranial neoplasm or arteriovenous malformation.
- Intracranial aneurysm, unless surgically treated >3 months.
- Major hemorrhage in past 21 days.
- Major surgery, serious trauma, lumbar puncture, arterial puncture at a noncompressible site, or biopsy of a parenchymal organ in last 14 days. Major surgical procedures include but are not limited to the following: major thoracic or abdominopelvic surgery, neurosurgery, major limb surgery, carotid endarterectomy or other vascular surgery, and organ transplant. For unlisted procedures, the operating surgeon should be consulted to assess the risk
- Presumed or documented history of vasculitis.
- Known systemic bleeding disorder (eg, von Willebrand's disease, hemophilia, others).
- Platelet count <100'000 cells/µL.
- Congenital or acquired coagulopathy (eg, secondary to anticoagulants) causing either of the following:
- Activated partial thromboplastin time (aPTT) prolongation greater than 2 seconds above the upper limit of normal for local laboratory, except if due to isolated factor XII deficiency. The use of protamine sulfate to reverse the heparin effect is not allowed.
- International normalized ratio (INR) ³1.4. Subjects receiving warfarin prior to entry are eligible provided INR is <1.4 and warfarin can be safely discontinued for at least 36-48 h.
- Potentially Interfering with Outcome Assessment
- Prestroke Barthel Index (BI) <95 or modified Rankin scale score (mRS) >1.
- Life expectancy <3 months.
- Other serious illness (eg, severe hepatic, cardiac, or renal failure; acute myocardial infarction; or a complex disease that may confound treatment assessment).
- Drug Related
- Treatment with rt-PA, Ancrod, or intra-arterial thrombolytic for the qualifying stroke or administration of intra-arterial or systemic thrombolytic therapy in last 7 days.
- Treatment with rt-PA is indicated and commercially available and, in the judgment of the investigator and patient, the risk/benefit ratio is acceptable for treatment with rt-PA.
- Need for antiplatelet agent (eg, aspirin, ticlopidine, clopidogrel, dipyridamole), unfractionated or low molecular weight heparin, direct thrombin inhibitor, Factor Xa inhibitor, oral anticoagulant, or NSAID (excluding COX-2 inhibitor) before the post study-agent head CT scan. Treatment with aspirin prior to randomization is not an exclusion criterion.
- Allergy or hypersensitivity reaction (including anaphylaxis) or clinically significant reaction (including thrombocytopenia) to administration of abciximab or other murine proteins, if known.
- Treatment with unfractionated or low molecular weight heparin, direct thrombin inhibitor, or Factor Xa inhibitor within 48 hours before randomization, irrespective of the aPTT results or the heparin dose received (with the exception of minimal heparin use to maintain an open IV infusion line, <100 units/day).
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Switzerland1 site
University of Zurich, Department of Neurology
Zurich, Canton of Zurich, 8091
About this study
Official title: Does Abciximab Save Hypoperfused Ischemic Brain Tissue in Wake-Up Stroke: A Placebo-Controlled, Randomized, MR Imaging Study
The purpose of the prospective, randomized, double blind, placebo-controlled multicenter pilot study is to evaluate the effectiveness of abciximab on rescuing the hypoperfused brain tissue, as assessed by MRI, and the relative safety of abciximab in patients with wake-up stroke.
Read the detailed description
Intravenous (IV) administration of recombinant tissue plasminogen activator (rt-PA) is the only approved therapy in patients with acute ischemic stroke presenting within 3 hours of symptom onset. Approximately 17-30% of ischemic strokes are found on awakening. Since stroke onset cannot be determined for patients who awake with stroke, they are de facto ineligible for thrombolytic therapy. Nevertheless, it is possible that some patients suffered their stroke within a few hours prior to become awake, and may thus be good candidates for thrombolysis. Combined diffusion- (DWI) and perfusion- (PWI) weighted MR imaging (MRI) is able to identify hypoperfused but still viable brain tissue, the potentially salvageable ischemic penumbra (PWI-DWI mismatch). A recent study has examined 34 patients with wake-up stroke and a median National Institute of Health Stroke Scale (NIHSS) score of 13 (range 6 to 22) with DWI and PWI. The authors found that 73% of patients presenting with non-lacunar stroke within 3 hours of waking from sleep had a PWI-DWI mismatch with larger hypoperfused areas. This imaging pattern may be associated with potential benefit from thrombolysis beyond the current 3-hour window. Induced or spontaneous reperfusion of brain areas with initial PWI hypoperfusion has been associated with reduced infarction and a favourable clinical outcome. A phase IIa placebo-controlled safety and pilot efficacy trial of abciximab in patients with acute ischemic stroke treated within 24 hours from symptoms onset found that abciximab caused no symptomatic intracranial hemorrhage and showed a trend toward a higher rate of patients with minimal residual disability1. Thus, abciximab may be an attractive therapy option in patients with wake-up stroke and a PWI-DWI mismatch.
The purpose of the prospective, randomized, double blind, placebo-controlled multicenter pilot study is to evaluate the effectiveness of abciximab on rescuing the hypoperfused brain tissue, as assessed by MRI, and the relative safety of abciximab in patients with wake-up stroke.
- Conditions
- Stroke
- Being tested
- Abciximab
- Keywords
- stroke, ischemic, acute ischemic stroke
- Medical subject headings
- Stroke, Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AbciximabDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
To investigate whether abciximab compared with placebo is able to save brain tissue as assessed by MRI performed prior to inclusion in the study and 5-7 days after stroke onset:
(PWI1 - FLAIR2) / PWI1 ("brain salvage index": area at risk not progressed into final infarct size)and (FLAIR2 - DWI1) / DWI1 (relative growth of infarct size from admission to days 5-7).
Secondary outcomes (6)
To compare abciximab and placebo with regard to the:
Proportion of mRS responders at 90 ± 14 days (mRS responder is defined as: mRS at 90 ± 14 days = 0 if baseline NIHSS score was 4-7, mRS at 90 ± 14 days <1 if baseline NIHSS score was 8-14, and mRS at 90 ± 14 days <2 if baseline NIHSS score was 15),
Functional outcome (as measured by the mRS and NIHSS, and all cause mortality at 90 ± 14 days),
Incidence of fatal ICH, non-fatal symptomatic parenchymal hemorrhage, or other symptomatic ICH through discharge/day 5,
Proportion of subjects with non-intracranial bleeding through discharge/day 5,
Ratio (DWI2-DWI1)/DWI1 for detecting new infarcts.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2005 (estimated)
- Study startMar 2005
- Study completionMay 2005
Why it stopped: Higher hemorrhage rates of Abciximab in ABESST II trial
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Single group
- Masking
- Double blind
- Enrolment
- 50 participants
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Investigators
- Ralf W. Baumgartner, MD, Principal investigator, University of ZurichMario Siebler, MD, Principal investigator, Heinrich Heine University Dusseldorf
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00167765
- Sponsor's protocol ID
- H4S-SZ-O056
- Status last verified
- May 2007
- First submitted
- 9 Sep 2005
- Last updated
- 3 May 2007
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Abciximab Save Hypoperfused Ischemic Brain Tissue in Wake-Up Stroke: A Placebo-Controlled, Randomized, MR Imaging Study
- ClinicalTrials.gov ID
- NCT00167765
- Acronym / sponsor ID
- H4S-SZ-O056
- Conditions
- Stroke
- Keywords
- stroke, ischemic, acute ischemic stroke
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Higher hemorrhage rates of Abciximab in ABESST II trial
- Enrolment
- 50 participants
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Collaborators
- Eli Lilly and Company
- Study start
- Mar 2005
- Study completion
- May 2005 (actual)
- First posted
- 14 Sep 2005 (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 the prospective, randomized, double blind, placebo-controlled multicenter pilot study is to evaluate the effectiveness of abciximab on rescuing the hypoperfused brain tissue, as assessed by MRI, and the relative safety of abciximab in patients with wake-up stroke.
Detailed description
Intravenous (IV) administration of recombinant tissue plasminogen activator (rt-PA) is the only approved therapy in patients with acute ischemic stroke presenting within 3 hours of symptom onset. Approximately 17-30% of ischemic strokes are found on awakening. Since stroke onset cannot be determined for patients who awake with stroke, they are de facto ineligible for thrombolytic therapy. Nevertheless, it is possible that some patients suffered their stroke within a few hours prior to become awake, and may thus be good candidates for thrombolysis. Combined diffusion- (DWI) and perfusion- (PWI) weighted MR imaging (MRI) is able to identify hypoperfused but still viable brain tissue, the potentially salvageable ischemic penumbra (PWI-DWI mismatch). A recent study has examined 34 patients with wake-up stroke and a median National Institute of Health Stroke Scale (NIHSS) score of 13 (range 6 to 22) with DWI and PWI. The authors found that 73% of patients presenting with non-lacunar stroke within 3 hours of waking from sleep had a PWI-DWI mismatch with larger hypoperfused areas. This imaging pattern may be associated with potential benefit from thrombolysis beyond the current 3-hour window. Induced or spontaneous reperfusion of brain areas with initial PWI hypoperfusion has been associated with reduced infarction and a favourable clinical outcome. A phase IIa placebo-controlled safety and pilot efficacy trial of abciximab in patients with acute ischemic stroke treated within 24 hours from symptoms onset found that abciximab caused no symptomatic intracranial hemorrhage and showed a trend toward a higher rate of patients with minimal residual disability1. Thus, abciximab may be an attractive therapy option in patients with wake-up stroke and a PWI-DWI mismatch.
The purpose of the prospective, randomized, double blind, placebo-controlled multicenter pilot study is to evaluate the effectiveness of abciximab on rescuing the hypoperfused brain tissue, as assessed by MRI, and the relative safety of abciximab in patients with wake-up stroke.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patient who awakes with an acute ischemic stroke in the anterior circulation.
- Planned start of study agent >3 hours and £6 hours from time of awakening and <1 hour after MRI mismatch diagnosis is established (cf. item 5 below).
- Pre-randomization NIHSS score of 4-20.
- Age >18 years.
- MRI showing a PWI-DWI mismatch defined by visual estimation, where the PWI lesion will be >130% of the DWI volume.
Key exclusion criteria (43 listed)
- Participation in another study with an investigational drug or device within the last 30 days.
- Prior participation in the present study, or planned participation in another trial.
- Symptoms suggestive of subarachnoid hemorrhage, even if MRI/CT scan is negative for hemorrhage.
- Women known to be pregnant, lactating, or having a positive or indeterminate pregnancy test.
- Stroke Related
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 |
|---|---|---|
| Abciximab | Drug | – |
Primary outcome
To investigate whether abciximab compared with placebo is able to save brain tissue as assessed by MRI performed prior to inclusion in the study and 5-7 days after stroke onset:
(PWI1 - FLAIR2) / PWI1 ("brain salvage index": area at risk not progressed into final infarct size)and (FLAIR2 - DWI1) / DWI1 (relative growth of infarct size from admission to days 5-7).
6 secondary outcomes
To compare abciximab and placebo with regard to the:
Proportion of mRS responders at 90 ± 14 days (mRS responder is defined as: mRS at 90 ± 14 days = 0 if baseline NIHSS score was 4-7, mRS at 90 ± 14 days <1 if baseline NIHSS score was 8-14, and mRS at 90 ± 14 days <2 if baseline NIHSS score was 15),
Functional outcome (as measured by the mRS and NIHSS, and all cause mortality at 90 ± 14 days),
Incidence of fatal ICH, non-fatal symptomatic parenchymal hemorrhage, or other symptomatic ICH through discharge/day 5,
Proportion of subjects with non-intracranial bleeding through discharge/day 5,
Ratio (DWI2-DWI1)/DWI1 for detecting new infarcts.
Results and safety
The study was stopped early (reason given: Higher hemorrhage rates of Abciximab in ABESST II trial). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2007.
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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.
Ralf W. Baumgartner, MD principal investigator
University of Zurich
Mario Siebler, MD principal investigator
Heinrich Heine University Dusseldorf
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Abciximab in people with Stroke, run by University of Zurich at 2 sites in 2 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 6 inclusion and 43 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 3 May 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany, Switzerland. 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. 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: Higher hemorrhage rates of Abciximab in ABESST II trial). 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?
To investigate whether abciximab compared with placebo is able to save brain tissue as assessed by MRI performed prior to inclusion in the study and 5-7 days after stroke onset:. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 May 2007.