The Strategy to Prevent Hemorrhage Associated With Anticoagulation in Renal Disease Management (STOP HARM) Trial (STOP-HARM)
Primary Purpose
Chronic Kidney Disease, Acute Bleeding, Cerebrovascular Stroke
Status
Withdrawn
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Watchman
Continued therapy with the prescribed oral anticoagulant
Sponsored by
About this trial
This is an interventional prevention trial for Chronic Kidney Disease
Eligibility Criteria
Inclusion Criteria:
- Age ≥18 years
- Severe chronic kidney disease: a. Receiving dialysis >90 days or b. Estimated glomerular filtration rate less than 30 ml/min/1.73m2 for >90 days as calculated by CKD-Epi
- History of persistent, paroxysmal or permanent atrial fibrillation documented by ECG within 12 months of randomization
- High risk of stroke: a. CHADS-VASC≥3 or, b. Prior ischemic stroke or TIA 2-24 months prior to randomization,
- Currently receiving chronic oral anticoagulation (vitamin K antagonist, Apixaban 2.5 mg bid or Rivaroxaban 15mg od) for atrial fibrillation
- Provides informed consent
Exclusion Criteria:
- Short life expectancy: a. > 90 years old or, b. Positive "surprise" question (Physician not surprised if patient died in the next 12 months)
- Stroke within the last 2 months
- Contraindications to withdrawal of anticoagulation (e.g. mechanical valve, recurrent venous thromboembolism)
- Contraindication to low-dose aspirin
- Contraindication to placement of Watchman device: a. Thrombus formation in left atrial appendage b. Severe mitral or aortic valvular disease c. Left atrial appendage diameter too small or too large to accommodate the device d. Pericardial effusion >2 mm e. Cardiac tumor
- Scheduled living related donor transplant
Sites / Locations
- Hamilton General Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Left atrial appendage occlusion
Continuation of prescribed anticoagulant
Arm Description
Patients receiving the Watchman device will have it placed via a percutaneous trans-septal approach under transesophageal echocardiographic and fluoroscopic guidance. Patients will be anticoagulated for at least 45 days after the procedure.
Patients continuing medical therapy will continue to take their previously prescribed oral anticoagulation (vitamin K antagonist, apixiban or rivaroxaban) for the duration of the study unless a medical reason to alter therapy occurs.
Outcomes
Primary Outcome Measures
Time from randomization to the first occurrence of major bleeding.
This evaluation will be based on a structured interview with the patient. In case of positive evaluation for the outcome more information will be obtained by hospital or physician.
Secondary Outcome Measures
Time from randomization to the first occurrence of ischemic stroke
This evaluation will be based on a structured interview with the patient. In case of positive evaluation for the outcome more information will be obtained by hospital or physician.
Time from randomization to the first occurrence of either ischemic stroke or non-central nervous system arterial embolism
This evaluation will be based on a structured interview with the patient. In case of positive evaluation for the outcome more information will be obtained by hospital or physician.
Time from randomization to the first occurrence of all-cause mortality
This evaluation will be based on a structured interview with the patient. In case of positive evaluation for the outcome more information will be obtained by hospital or physician.
Time from randomization to the first occurrence of a life threatening bleed
This evaluation will be based on a structured interview with the patient. In case of positive evaluation for the outcome more information will be obtained by hospital or physician.
Bleeding directly caused by implantation of Watchman Device
This evaluation will be based on a structured interview with the patient. In case of positive evaluation for the outcome more information will be obtained by hospital or physician.
Device complications directly caused by implantation of Watchman Device
This evaluation will be based on a structured interview with the patient. In case of positive evaluation for the outcome more information will be obtained by hospital or physician.
Health related quality of life (EQ-5D-5L)
This evaluation will be based on a structured interview with the patient.
Full Information
NCT ID
NCT02885545
First Posted
June 24, 2016
Last Updated
March 26, 2018
Sponsor
Population Health Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT02885545
Brief Title
The Strategy to Prevent Hemorrhage Associated With Anticoagulation in Renal Disease Management (STOP HARM) Trial
Acronym
STOP-HARM
Official Title
The Strategy to Prevent Hemorrhage Associated With Anticoagulation in Renal Disease Management (STOP HARM) Trial
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Withdrawn
Why Stopped
Failure to recruit any participants in more than one year of recruiting.
Study Start Date
September 2016 (Anticipated)
Primary Completion Date
March 5, 2018 (Actual)
Study Completion Date
March 5, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Population Health Research Institute
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Patients with severe chronic kidney disease (CKD) who develop atrial fibrillation are at high risk for stroke. The use of blood thinking medication in dialysis patients is controversial and warfarin carries a serious risk for major bleeding.
The Watchman device may be an ideal therapy for this population as after implantation it allows for the discontinuation of blood thinners, thereby reducing the risk of bleeding.
Detailed Description
An estimated 25 million North American's have chronic kidney disease (CKD) including 600,000 that require dialysis for end-stage renal disease.The importance of CKD is underscored by the poor survival, frequent hospitalizations and impaired health related quality of life of patients with CKD.
Stroke is an important cause of morbidity, mortality and suffering for patients with CKD. Stroke is approximately 5 to 10 times more common in patients with advanced CKD compared to non-CKD patients. Atrial fibrillation (AF), the most important risk factor for stroke, occurs in up to 20.4% of patients with advanced CKD. Observational studies suggest anywhere from an approximate 56% relative risk reduction to a 2-fold increase in the risk of stroke with warfarin. Furthermore, the risk of bleeding in patients with advanced CKD is roughly 5-fold higher than patients without CKD. Although OAC may not prevent strokes in patients with advanced CKD, it still increases the risk of major bleeding by 1.4 fold.
New stroke prevention strategies in patients with CKD and AF are urgently needed. An effective strategy must reduce the risk of thromboembolic events while not increasing the risk of bleeding substantially. Left atrial appendage occlusion (LAAO) with devices such as the Watchman, represent a unique opportunity to accomplish effective stroke prevention while mitigating the risk of bleeding in this patient population.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Disease, Acute Bleeding, Cerebrovascular Stroke
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Left atrial appendage occlusion
Arm Type
Experimental
Arm Description
Patients receiving the Watchman device will have it placed via a percutaneous trans-septal approach under transesophageal echocardiographic and fluoroscopic guidance. Patients will be anticoagulated for at least 45 days after the procedure.
Arm Title
Continuation of prescribed anticoagulant
Arm Type
Active Comparator
Arm Description
Patients continuing medical therapy will continue to take their previously prescribed oral anticoagulation (vitamin K antagonist, apixiban or rivaroxaban) for the duration of the study unless a medical reason to alter therapy occurs.
Intervention Type
Device
Intervention Name(s)
Watchman
Intervention Description
If the patient is randomized to the Intervention Arm of the study the Watchman device will be implanted into the left atrial appendage of the heart
Intervention Type
Drug
Intervention Name(s)
Continued therapy with the prescribed oral anticoagulant
Other Intervention Name(s)
Standard of care
Intervention Description
If the patient is randomized to the control arm of the study, they will continue taking the oral anticoagulant that has been prescribed (vitamin K antagonist, Apixiban 2.5mg bid or Rivaroxaban 15mg od)
Primary Outcome Measure Information:
Title
Time from randomization to the first occurrence of major bleeding.
Description
This evaluation will be based on a structured interview with the patient. In case of positive evaluation for the outcome more information will be obtained by hospital or physician.
Time Frame
Approximately 5 years
Secondary Outcome Measure Information:
Title
Time from randomization to the first occurrence of ischemic stroke
Description
This evaluation will be based on a structured interview with the patient. In case of positive evaluation for the outcome more information will be obtained by hospital or physician.
Time Frame
Approximately 5 years
Title
Time from randomization to the first occurrence of either ischemic stroke or non-central nervous system arterial embolism
Description
This evaluation will be based on a structured interview with the patient. In case of positive evaluation for the outcome more information will be obtained by hospital or physician.
Time Frame
Approximately 5 years
Title
Time from randomization to the first occurrence of all-cause mortality
Description
This evaluation will be based on a structured interview with the patient. In case of positive evaluation for the outcome more information will be obtained by hospital or physician.
Time Frame
Approximately 5 years
Title
Time from randomization to the first occurrence of a life threatening bleed
Description
This evaluation will be based on a structured interview with the patient. In case of positive evaluation for the outcome more information will be obtained by hospital or physician.
Time Frame
Approximately 5 years
Title
Bleeding directly caused by implantation of Watchman Device
Description
This evaluation will be based on a structured interview with the patient. In case of positive evaluation for the outcome more information will be obtained by hospital or physician.
Time Frame
30 days
Title
Device complications directly caused by implantation of Watchman Device
Description
This evaluation will be based on a structured interview with the patient. In case of positive evaluation for the outcome more information will be obtained by hospital or physician.
Time Frame
30 days
Title
Health related quality of life (EQ-5D-5L)
Description
This evaluation will be based on a structured interview with the patient.
Time Frame
Approximately 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥18 years
Severe chronic kidney disease: a. Receiving dialysis >90 days or b. Estimated glomerular filtration rate less than 30 ml/min/1.73m2 for >90 days as calculated by CKD-Epi
History of persistent, paroxysmal or permanent atrial fibrillation documented by ECG within 12 months of randomization
High risk of stroke: a. CHADS-VASC≥3 or, b. Prior ischemic stroke or TIA 2-24 months prior to randomization,
Currently receiving chronic oral anticoagulation (vitamin K antagonist, Apixaban 2.5 mg bid or Rivaroxaban 15mg od) for atrial fibrillation
Provides informed consent
Exclusion Criteria:
Short life expectancy: a. > 90 years old or, b. Positive "surprise" question (Physician not surprised if patient died in the next 12 months)
Stroke within the last 2 months
Contraindications to withdrawal of anticoagulation (e.g. mechanical valve, recurrent venous thromboembolism)
Contraindication to low-dose aspirin
Contraindication to placement of Watchman device: a. Thrombus formation in left atrial appendage b. Severe mitral or aortic valvular disease c. Left atrial appendage diameter too small or too large to accommodate the device d. Pericardial effusion >2 mm e. Cardiac tumor
Scheduled living related donor transplant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carlos Morillo, MD
Organizational Affiliation
Population Health Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hamilton General Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8L 2X2
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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The Strategy to Prevent Hemorrhage Associated With Anticoagulation in Renal Disease Management (STOP HARM) Trial
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