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Canadian Pradaxa Acute Stroke Safety Study (CPASS)

This study is currently recruiting participants.
Verified October 2017 by Ken Butcher, University of Alberta
Sponsor:
ClinicalTrials.gov Identifier:
NCT02415855
First Posted: April 14, 2015
Last Update Posted: October 26, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
Ken Butcher, University of Alberta
  Purpose

Study Design:

This is a multicentre, prospective, open-label, single arm, phase IV registry study. No additional procedures are included in the study. Standard clinical data will be collected. This will include a physical examination and NIHSS score assessment at baseline. In addition, all neuro-imaging will be collected. Standard imaging includes a non-contrast CT brain at baseline and 7±2 days post-treatment. Repeat NIHSS score assessment at the time of the 7 day CT scan. Repeat clinical and NIHSS score assessment 30 days post-enrolment will also be collected when performed as part of standard care.

Study Objectives:

  1. Demonstrate the safety of early dabigatran initiation after minor stroke/TIA in patients with atrial fibrillation.
  2. Determine the frequency of asymptomatic hemorrhagic transformation after 7 days of dabigatran treatment following stroke/TIA
  3. Determine the effect of asymptomatic hemorrhagic transformation on functional and neurological outcome at 30 days.

Condition Intervention
Ischemic Attack, Transient Stroke Drug: Dabigatran

Study Type: Observational [Patient Registry]
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 30 Days
Official Title: Canadian Pradaxa Acute Stroke Safety Study

Resource links provided by NLM:


Further study details as provided by Ken Butcher, University of Alberta:

Primary Outcome Measures:
  • Symptomatic Hemorrhagic Transformation Rate (PH2) [ Time Frame: 30 days post-treatment ]
    Symptomatic Hemorrhagic Transformation Rate (PH2) associated with clinical deterioration, defined as worsening of NIHSS score of 4 or more points within 30 days of initiating dabigatran therapy.


Secondary Outcome Measures:
  • Any parenchymal haemorrhage (PH1 or PH2) [ Time Frame: 7 days post-enrollemnt ]
    Any parenchymal haemorrhage (PH1 or PH2) on follow-up CT scan at 7±2 days post-enrolment.

  • Symptomatic hemorrhagic transformation rate [ Time Frame: 30 days post enrolment ]
    Symptomatic hemorrhagic transformation rate (defined as above) in patients treated with warfarin prior to the index stroke/TIA.

  • Recurrent TIA/Ischemic Stroke [ Time Frame: 30 days post enrolment ]
  • Systemic hemorrhagic complication rate [ Time Frame: 30 days post enrolment ]

Estimated Enrollment: 500
Study Start Date: March 2015
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Dabigatran
    Other Name: Pradaxa
Detailed Description:

Study Aim and Design:

The primary aim of the CPASS registry is to demonstrate the safety of early anticoagulation with dabigatran following cardioembolic stroke. CPASS is a prospective open label single arm observational study. Safety will be established by demonstrating low rates of hemorrhage in this setting.

Administrative Structure:

CPASS is a Canadian Stroke Consortium led study. The study coordinating centre is at the University of Alberta. Case report forms and data monitoring will be completed electronically, using an online EDC system. All imaging data will be read centrally at the Stroke Imaging Laboratory at the University of Alberta.

Study Design Considerations:

A randomized controlled design was considered (dabigatran versus warfarin). This is considered impractical for a number of reasons. Novel oral anticoagulants are recommended as first line agents for stroke prevention in AF patients by the Canadian Cardiovascular Society.19 These agents are associated with improved safety with respect to bleeding complications. This makes randomization of a patient to warfarin who would otherwise be prescribed dabigatran somewhat ethically dubious. In addition, a randomized design would necessitate a very large study, which would not be completed in a reasonable period of time. A registry design allows us to address the question of safety in a systematic fashion. A safety threshold has been defined for any anticoagulant use early after stroke, based on the rates of warfarin-associated intracranial hemorrhage, which have been reported to be 0.5 to 2.5 per 100 patient years.20-24 The registry design therefore permits determination of whether or not dabigatran is within this threshold. Finally, the systematic collection of clinical and imaging data will allow us to determine any risk factors for hemorrhagic transformation associated with early anticoagulation.

Prescribed Study Treatments:

Patients in whom dabigatran is initiated within 14 days of TIA/stroke symptom onset will be included in the registry. Patients will be treated either at a dose of 110 mg BID or 150 mg BID. The dose and timing of initiation of therapy within that 14 day window will be determined by the treating physician. The factors related to physician choice of initiation time (relative to symptom onset) will be recorded.

Visit Schedule / Clinical Data Collection:

Standard clinical assessments and data will be collected. This will include baseline National Institutes of Health Stroke Scale NIHSS, Glasgow Coma Scale (GCS) and vital signs, which will be recorded in a case report form. Stroke risk factors, past medical history and medications, baseline complete blood count, coagulation profile and renal function tests will also be recorded. CHADS2 and CHADSVaSC scores will also be recorded. Clinical endpoints will be ischemic stroke or intracranial hemorrhage within 30 days of anticoagulant initiation. All cerebral ischemic and intracranial hemorrhagic endpoints will be centrally adjudicated from anonymized clinical records, with the intracranial hemorrhages classified as described above. A data collection form will be filled out for each subject at 30 days post-enrolment indicating clinical status and occurrence of outcome events.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Minor Stroke (NIHSS Score ≤ 3) and Transient Ischemic Attack Patients ≥ 18 years of age, with a known history of or demonstrated atrial fibrillation (paroxysmal or persistent), who can be treated with dabigatran following stroke.
Criteria

Inclusion Criteria:

  1. All patients will be ≥ 18 years of age.
  2. Minor ischemic stroke, defined as NIHSS score ≤ 3. Transient Ischemic Attack (TIA), defined as acute focal neurological deficits, with complete resolution of symptoms within 24 h of onset. In cases where onset time cannot be established, it will be considered to be the time when the patient was last known to be well.
  3. Atrial Fibrillation (AF, paroxysmal or persistent). AF must be confirmed with ECG/Holter monitor, or by history All patients prescribed dabigatran according to the Canadian product label by the treating physician following their stroke/TIA. The decision to treat with dabigatran and the timing of the first dose will be determined by the attending physician, independent of the registry. All patients will have a CT scan or MRI, with findings consistent with an ischemic etiology of symptoms.
  4. Ability to obtain informed consent obtained from patient or legally authorized representative.

Exclusion Criteria:

  1. Acute or chronic renal failure, defined as eGFR <30 ml/min (Cockcroft Gault formula).
  2. Known hypersensitivity to dabigatran or any other contraindication to dabigatran therapy, as per Canadian label information.
  3. Prior treatment with dabigatran or any other novel oral anticoagulant (including all Factor Xa antagonists). Treatment with warfarin prior to the stroke/TIA is acceptable, but enrolment cannot begin until the INR is ≤1.5.
  4. Prior symptomatic ischemic stroke (TIA is not an exclusion criterion)
  5. Any significant ongoing systemic bleeding risk, i.e. active GI/GU bleeding or recent major surgery.
  6. Clinically significant recent past history or clinical presentation of ICH, subarachnoid haemorrhage (SAH), arterio-venous (AV) malformation, aneurysm, or cerebral neoplasm. At the discretion of each Investigator.
  7. Hereditary or acquired hemorrhagic diathesis.
  8. Anticipated inability to comply with follow up.
  9. Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02415855


Contacts
Contact: Ken Butcher, MD, PhD 780-248-1927 ken.butcher@ualberta.ca

Locations
Canada, Alberta
University of Alberta Recruiting
Edmonton, Alberta, Canada, T6G 2B7
Contact: Ken S Butcher, MD, PhD    780-248-1927    ken.butcher@ualberta.ca   
Principal Investigator: Ken S Butcher, MD, PhD         
Canada, Ontario
Ottawa Hospital Research Institute Recruiting
Ottawa, Ontario, Canada, K1Y 4E9
Contact: Dar Dowlatshahi, MD    613-761-4709    ddowlat@toh.on.ca   
Principal Investigator: Dar Dowlatshahi, MD         
Sponsors and Collaborators
University of Alberta
Boehringer Ingelheim
  More Information

Responsible Party: Ken Butcher, Assistant Professor, University of Alberta
ClinicalTrials.gov Identifier: NCT02415855     History of Changes
Other Study ID Numbers: CSC2012-01
First Submitted: April 9, 2015
First Posted: April 14, 2015
Last Update Posted: October 26, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Stroke
Ischemic Attack, Transient
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Ischemia
Dabigatran
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants