CPASS: Canadian Pradaxa Acute Stroke Safety Study

• Sponsor: University of Alberta (Other)
• Overall Status: Completed
• CT.gov ID: NCT02415855
• Collaborator: Boehringer Ingelheim (Industry)
• Enrollment: 101
• Locations: 2
• Duration (Months): 38.6
• Patients Per Site: 50.5
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Ischemic Attack, Transient; Stroke	Drug: Dabigatran

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.

Study Design

• Study Type: Observational [Patient Registry]
• Actual Enrollment: 101 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Canadian Pradaxa Acute Stroke Safety Study
• Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: Mar 31, 2018
• Actual Study Completion Date: May 18, 2018

Outcome Measures

Primary Outcome Measures

1. Symptomatic Hemorrhagic Transformation Rate (PH2) [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

1. Any Parenchymal Haemorrhage (PH1 or PH2) [7 days post-enrollment]

   Any parenchymal haemorrhage (PH1 or PH2) on follow-up CT scan at 7±2 days post-enrolment.

2. Symptomatic Hemorrhagic Transformation Rate [30 days post enrolment]

   Symptomatic hemorrhagic transformation rate (defined as above) in patients treated with warfarin prior to the index stroke/TIA.

3. Recurrent TIA/Ischemic Stroke [30 days post enrolment]

   Monitoring and documentation of recurrent TIAs or Ischemic Stroke occuring in participants of both arms

4. Systemic Hemorrhagic Complication Rate [30 days post enrolment]

   Monitoring and documentation of the number of the rate of hemorrhagic complications for participants in either arm of the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	University of Alberta	Edmonton	Alberta	Canada	T6G 2B7
2	Ottawa Hospital Research Institute	Ottawa	Ontario	Canada	K1Y 4E9

Sponsors and Collaborators

• University of Alberta
• Boehringer Ingelheim

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 29, 2014

More Information

Publications

None provided.

• Responsible Party: University of Alberta
• ClinicalTrials.gov Identifier: NCT02415855
• Other Study ID Numbers: CSC2012-01
• First Posted: Apr 14, 2015
• Last Update Posted: Jun 19, 2020
• Last Verified: Jun 1, 2020

• Additional relevant MeSH terms: Stroke; Ischemic Attack, Transient; Dabigatran

Study Results

Participant Flow

Recruitment Details	Participants were approached after the treating physician's decision to treat with dabigatran within 14 days of stroke/TIA, independent of the registry.

Arm/Group Title	Dabigatran 110 mg BID	Dabigatran 150mg BID
Arm/Group Description	Participants with an estimated glomerular filtration rate 30-50 ml/min and/or age 80 years received Dabigatran 110 mg twice a day.	Participants who were under 80 yrs of age and who had an estimated glomerular filtration rate of greater than 50 ml/min were treated with dabigatran 150mg BID.
Period Title: Overall Study
STARTED	37	64
COMPLETED	34	62
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Dabigatran 110 mg BID	Dabigatran 150mg BID	Total
Arm/Group Description	Participants with an estimated glomerular filtration rate 30-50 ml/min and/or age 80 years received Dabigatran 110 mg twice a day.	Participants who were under 80 yrs of age and who had an estimated glomerular filtration rate of greater than 50 ml/min were treated with dabigatran 150mg BID.	Total of all reporting groups
Overall Participants	37	64	101
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	18 48.6%	30 46.9%	48 47.5%
>=65 years	19 51.4%	34 53.1%	53 52.5%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	72	72	72
Sex: Female, Male (Count of Participants)
Female	13 35.1%	22 34.4%	35 34.7%
Male	24 64.9%	42 65.6%	66 65.3%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (Count of Participants)
Canada	37 100%	64 100%	101 100%

Outcome Measures

1. Primary Outcome

Title	Symptomatic Hemorrhagic Transformation Rate (PH2)
Description	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.
Time Frame	30 days post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dabigatran 110 mg BID	Dabigatran 150mg BID
Arm/Group Description	Participants with an estimated glomerular filtration rate 30-50 ml/min and/or age 80 years received Dabigatran 110 mg twice a day.	Participants who were under 80 yrs of age and who had an estimated glomerular filtration rate of greater than 50 ml/min were treated with dabigatran 150mg BID.
Measure Participants	37	64
Count of Participants [Participants]	0 0%	0 0%

2. Secondary Outcome

Title	Any Parenchymal Haemorrhage (PH1 or PH2)
Description	Any parenchymal haemorrhage (PH1 or PH2) on follow-up CT scan at 7±2 days post-enrolment.
Time Frame	7 days post-enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dabigatran 110 mg BID	Dabigatran 150mg BID
Arm/Group Description	Participants with an estimated glomerular filtration rate 30-50 ml/min and/or age 80 years received Dabigatran 110 mg twice a day.	Participants who were under 80 yrs of age and who had an estimated glomerular filtration rate of greater than 50 ml/min were treated with dabigatran 150mg BID.
Measure Participants	37	64
Count of Participants [Participants]	3 8.1%	3 4.7%

3. Secondary Outcome

Title	Symptomatic Hemorrhagic Transformation Rate
Description	Symptomatic hemorrhagic transformation rate (defined as above) in patients treated with warfarin prior to the index stroke/TIA.
Time Frame	30 days post enrolment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dabigatran 110 mg BID	Dabigatran 150mg BID
Arm/Group Description	Participants with an estimated glomerular filtration rate 30-50 ml/min and/or age 80 years received Dabigatran 110 mg twice a day.	Participants who were under 80 yrs of age and who had an estimated glomerular filtration rate of greater than 50 ml/min were treated with dabigatran 150mg BID.
Measure Participants	37	64
Count of Participants [Participants]	0 0%	0 0%

4. Secondary Outcome

Title	Recurrent TIA/Ischemic Stroke
Description	Monitoring and documentation of recurrent TIAs or Ischemic Stroke occuring in participants of both arms
Time Frame	30 days post enrolment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dabigatran 110 mg BID	Dabigatran 150mg BID
Arm/Group Description	Participants with an estimated glomerular filtration rate 30-50 ml/min and/or age 80 years received Dabigatran 110 mg twice a day.	Participants who were under 80 yrs of age and who had an estimated glomerular filtration rate of greater than 50 ml/min were treated with dabigatran 150mg BID.
Measure Participants	37	64
Count of Participants [Participants]	2 5.4%	2 3.1%

5. Secondary Outcome

Title	Systemic Hemorrhagic Complication Rate
Description	Monitoring and documentation of the number of the rate of hemorrhagic complications for participants in either arm of the study.
Time Frame	30 days post enrolment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dabigatran 110 mg BID	Dabigatran 150mg BID
Arm/Group Description	Participants with an estimated glomerular filtration rate 30-50 ml/min and/or age 80 years received Dabigatran 110 mg twice a day.	Participants who were under 80 yrs of age and who had an estimated glomerular filtration rate of greater than 50 ml/min were treated with dabigatran 150mg BID.
Measure Participants	37	64
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	30 days from start of medication.
Arm/Group Title	Dabigatran 110 mg BID		Dabigatran 150mg BID
Arm/Group Description	Participants with an estimated glomerular filtration rate 30-50 ml/min and/or age 80 years received Dabigatran 110 mg twice a day.		Participants who were under 80 yrs of age and who had an estimated glomerular filtration rate of greater than 50 ml/min were treated with dabigatran 150mg BID.
All Cause Mortality
	Dabigatran 110 mg BID		Dabigatran 150mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/37 (2.7%)		0/64 (0%)
Serious Adverse Events
	Dabigatran 110 mg BID		Dabigatran 150mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/37 (2.7%)		0/64 (0%)
Nervous system disorders
Recurrent Stroke	1/37 (2.7%)	1	0/64 (0%)	0
Other (Not Including Serious) Adverse Events
	Dabigatran 110 mg BID		Dabigatran 150mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/37 (2.7%)		1/64 (1.6%)
Endocrine disorders
Bleeding per rectum	1/37 (2.7%)	1	0/64 (0%)	0
Nervous system disorders
Sensory loss/Paresthesias, weak arms and headaches	0/37 (0%)	0	1/64 (1.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.