The Strategy to Prevent Hemorrhage Associated With Anticoagulation in Renal Disease Management (STOP HARM) Trial (STOP-HARM)

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.

Study Overview

• Status: Withdrawn
• Conditions: Chronic Kidney Disease; Cerebrovascular Stroke; Acute Bleeding
• Intervention / Treatment: Device: Watchman; Drug: Continued therapy with the prescribed oral anticoagulant

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.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥18 years
2. 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
3. History of persistent, paroxysmal or permanent atrial fibrillation documented by ECG within 12 months of randomization
4. High risk of stroke: a. CHADS-VASC≥3 or, b. Prior ischemic stroke or TIA 2-24 months prior to randomization,
5. Currently receiving chronic oral anticoagulation (vitamin K antagonist, Apixaban 2.5 mg bid or Rivaroxaban 15mg od) for atrial fibrillation
6. Provides informed consent

Exclusion Criteria:

1. Short life expectancy: a. > 90 years old or, b. Positive "surprise" question (Physician not surprised if patient died in the next 12 months)
2. Stroke within the last 2 months
3. Contraindications to withdrawal of anticoagulation (e.g. mechanical valve, recurrent venous thromboembolism)
4. Contraindication to low-dose aspirin
5. 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
6. Scheduled living related donor transplant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Left atrial appendage occlusion; 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.	Device: Watchman; 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
Active Comparator: Continuation of prescribed anticoagulant; 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.	Drug: Continued therapy with the prescribed oral anticoagulant; 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); Other Names: Standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Approximately 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Approximately 5 years
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.	Approximately 5 years
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.	Approximately 5 years
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.	Approximately 5 years
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.	30 days
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.	30 days
Health related quality of life (EQ-5D-5L)	This evaluation will be based on a structured interview with the patient.	Approximately 5 years

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Investigators: Principal Investigator: Carlos Morillo, MD, Population Health Research Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2016
• Primary Completion (Actual): March 5, 2018
• Study Completion (Actual): March 5, 2018

Study Registration Dates

• First Submitted: June 24, 2016
• First Submitted That Met QC Criteria: August 26, 2016
• First Posted (Estimate): August 31, 2016

Study Record Updates

• Last Update Posted (Actual): March 29, 2018
• Last Update Submitted That Met QC Criteria: March 26, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Urologic Diseases; Renal Insufficiency; Stroke; Kidney Diseases; Renal Insufficiency, Chronic; Hemorrhage; Anticoagulants
• Other Study ID Numbers: STOP HARM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided