Trial Outcomes & Findings for Evaluation of the WATCHMAN Left Atrial Appendage (LAA) Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy (NCT NCT01182441)

NCT ID: NCT01182441

Last Updated: 2018-07-26

Results Overview

7-Day procedure rate of death, ischemic stroke, systemic embolism and complications requiring major cardiovascular or endovascular intervention.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 407 participants
• Primary outcome timeframe: 7-Day
• Results posted on: 2018-07-26

Participant Flow

Participant milestones

Measure	WATCHMAN Subjects assigned to receive the WATCHMAN device. WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology	Warfarin Subjects assigned to warfarin therapy. Warfarin: Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0
Overall Study STARTED	269	138
Overall Study COMPLETED	49	19
Overall Study NOT COMPLETED	220	119

Reasons for withdrawal

Measure	WATCHMAN Subjects assigned to receive the WATCHMAN device. WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology	Warfarin Subjects assigned to warfarin therapy. Warfarin: Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0
Overall Study Patient Still in Follow-up	152	72
Overall Study Death	37	25
Overall Study Implant Attempt Unsuccessful	13	0
Overall Study Lost to Follow-up	5	8
Overall Study Withdrawal by Subject	6	13
Overall Study Implant Not Attempted	4	0
Overall Study Adverse Event	2	0
Overall Study Physician Decision	1	1

Baseline Characteristics

Evaluation of the WATCHMAN Left Atrial Appendage (LAA) Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy

Baseline characteristics by cohort

Measure	WATCHMAN n=269 Participants Subjects assigned to receive the WATCHMAN device. WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology	Warfarin n=138 Participants Subjects assigned to warfarin therapy. Warfarin: Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0	Total n=407 Participants Total of all reporting groups
Age, Continuous	74.0 years STANDARD_DEVIATION 7.4 • n=5 Participants	74.9 years STANDARD_DEVIATION 7.2 • n=7 Participants	74.3 years STANDARD_DEVIATION 7.4 • n=5 Participants
Sex: Female, Male Female	87 Participants n=5 Participants	35 Participants n=7 Participants	122 Participants n=5 Participants
Sex: Female, Male Male	182 Participants n=5 Participants	103 Participants n=7 Participants	285 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Black/Aftrican American	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	253 Participants n=5 Participants	131 Participants n=7 Participants	384 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic/Latino	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Native American Indian/Alaskan Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	269 participants n=5 Participants	138 participants n=7 Participants	407 participants n=5 Participants
CHADS2 Stroke Risk Score	2.6 scores on a scale STANDARD_DEVIATION 1.0 • n=5 Participants	2.6 scores on a scale STANDARD_DEVIATION 1.0 • n=7 Participants	2.6 scores on a scale STANDARD_DEVIATION 1.0 • n=5 Participants

PRIMARY outcome

Timeframe: 7-Day

7-Day procedure rate of death, ischemic stroke, systemic embolism and complications requiring major cardiovascular or endovascular intervention.

Outcome measures

Measure	WATCHMAN n=269 Participants Subjects assigned to receive the WATCHMAN device. WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology	Warfarin Subjects assigned to warfarin therapy. Warfarin: Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0
Primary Safety Endpoint (Device Group Only)	6 Participants	—

PRIMARY outcome

Timeframe: 18 month rate

The endpoint was analyzed using a Bayesian piecewise exponential model with the historical priors based on data from the previous pivotal study PROTECT AF. This was a non-inferiority design with comparison of rate ratio of 18-month event rates of the Device and Control groups. The 18-month rate represents the probability of an event occurring within 18 months, and the 18-month rate ratio is a mean of the rate ratios. The primary endpoint was based on a calculation of the probability of events at 18 months but the statistical piecewise hazards model does not require the observation of any subjects out to 18-months.

Outcome measures

Measure	WATCHMAN n=269 Participants Subjects assigned to receive the WATCHMAN device. WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology	Warfarin n=138 Participants Subjects assigned to warfarin therapy. Warfarin: Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0
Composite of Stroke, Systemic Embolism, and Death (Cardiovascular and Unknown)	0.064 Probability of events within 18 months	0.063 Probability of events within 18 months

PRIMARY outcome

Timeframe: Day 8 to 18-months

Composite of ischemic stroke or systemic embolism excluding events that occurred in the first 7 days following randomization

Outcome measures

Measure	WATCHMAN n=269 Participants Subjects assigned to receive the WATCHMAN device. WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology	Warfarin n=138 Participants Subjects assigned to warfarin therapy. Warfarin: Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0
Composite of Ischemic Stroke or Systemic Embolism	0.0253 Probability of events within 18-months	0.0200 Probability of events within 18-months

Adverse Events

WATCHMAN

Serious events: 86 serious events

Other events: 38 other events

Deaths: 37 deaths

Warfarin

Serious events: 44 serious events

Other events: 10 other events

Deaths: 25 deaths

Serious adverse events

Measure	WATCHMAN n=269 participants at risk Subjects assigned to receive the WATCHMAN device. WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology	Warfarin n=138 participants at risk Subjects assigned to warfarin therapy. Warfarin: Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0
Vascular disorders AV fistula	0.37% 1/269 • Number of events 1 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
Blood and lymphatic system disorders Anemia requiring transfusion	1.1% 3/269 • Number of events 3 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
Blood and lymphatic system disorders Bleeding, other	0.00% 0/269 • Randomization through 5-years	1.4% 2/138 • Number of events 2 • Randomization through 5-years
Injury, poisoning and procedural complications Cardiac perforation	0.37% 1/269 • Number of events 1 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
General disorders Cranial bleed	0.37% 1/269 • Number of events 1 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
General disorders Death	13.4% 36/269 • Number of events 36 • Randomization through 5-years	17.4% 24/138 • Number of events 24 • Randomization through 5-years
Injury, poisoning and procedural complications Device embolization	0.74% 2/269 • Number of events 2 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
General disorders Device thrombus	0.37% 1/269 • Number of events 1 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
Ear and labyrinth disorders Epistaxis	0.74% 2/269 • Number of events 2 • Randomization through 5-years	1.4% 2/138 • Number of events 2 • Randomization through 5-years
Gastrointestinal disorders Gastrointestinal bleeding	7.1% 19/269 • Number of events 19 • Randomization through 5-years	8.7% 12/138 • Number of events 12 • Randomization through 5-years
Blood and lymphatic system disorders Hematoma	0.74% 2/269 • Number of events 2 • Randomization through 5-years	0.72% 1/138 • Number of events 1 • Randomization through 5-years
Gastrointestinal disorders Hematuria	0.37% 1/269 • Number of events 1 • Randomization through 5-years	1.4% 2/138 • Number of events 2 • Randomization through 5-years
Infections and infestations Infection	1.1% 3/269 • Number of events 3 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
Blood and lymphatic system disorders Major bleeding requiring transfusion	2.2% 6/269 • Number of events 6 • Randomization through 5-years	1.4% 2/138 • Number of events 2 • Randomization through 5-years
General disorders Other study related	2.2% 6/269 • Number of events 7 • Randomization through 5-years	0.72% 1/138 • Number of events 1 • Randomization through 5-years
Injury, poisoning and procedural complications Pericardial effusion with cardiac tamponade	1.5% 4/269 • Number of events 4 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
Vascular disorders Pseudoaneurysm	0.37% 1/269 • Number of events 1 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
Gastrointestinal disorders Rectal bleeding	0.74% 2/269 • Number of events 2 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.74% 2/269 • Number of events 2 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
Respiratory, thoracic and mediastinal disorders Respiratory insufficiency	0.37% 1/269 • Number of events 1 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
Cardiac disorders Hemorrhagic stroke	0.74% 2/269 • Number of events 2 • Randomization through 5-years	2.2% 3/138 • Number of events 3 • Randomization through 5-years
Cardiac disorders Ischemic stroke	5.6% 15/269 • Number of events 16 • Randomization through 5-years	2.9% 4/138 • Number of events 4 • Randomization through 5-years
Blood and lymphatic system disorders Subdural hematoma	0.74% 2/269 • Number of events 2 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
Cardiac disorders Systemic embolism	0.37% 1/269 • Number of events 1 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
Cardiac disorders Transient ischemic attack	1.9% 5/269 • Number of events 6 • Randomization through 5-years	1.4% 2/138 • Number of events 2 • Randomization through 5-years

Other adverse events

Measure	WATCHMAN n=269 participants at risk Subjects assigned to receive the WATCHMAN device. WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology	Warfarin n=138 participants at risk Subjects assigned to warfarin therapy. Warfarin: Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0
Blood and lymphatic system disorders Anemia requiring transfusion	1.5% 4/269 • Number of events 5 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
Blood and lymphatic system disorders Bleeding, other	0.00% 0/269 • Randomization through 5-years	1.4% 2/138 • Number of events 2 • Randomization through 5-years
General disorders Device thrombus	5.6% 15/269 • Number of events 16 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
Ear and labyrinth disorders Epistaxis	1.9% 5/269 • Number of events 5 • Randomization through 5-years	0.72% 1/138 • Number of events 2 • Randomization through 5-years
Gastrointestinal disorders Gastrointestinal bleeding	0.74% 2/269 • Number of events 2 • Randomization through 5-years	1.4% 2/138 • Number of events 3 • Randomization through 5-years
Gastrointestinal disorders Hematuria	0.37% 1/269 • Number of events 1 • Randomization through 5-years	2.2% 3/138 • Number of events 3 • Randomization through 5-years
General disorders Oral bleeding	0.74% 2/269 • Number of events 2 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
General disorders Other study related	0.74% 2/269 • Number of events 2 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
Cardiac disorders Pericardial effusion, non-serious	0.74% 2/269 • Number of events 2 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
Vascular disorders Pseudoaneurysm	0.74% 2/269 • Number of events 2 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
Gastrointestinal disorders Rectal bleeding	0.74% 2/269 • Number of events 2 • Randomization through 5-years	0.00% 0/138 • Randomization through 5-years
Cardiac disorders Transient ischemic attack	0.74% 2/269 • Number of events 2 • Randomization through 5-years	1.4% 2/138 • Number of events 2 • Randomization through 5-years

Additional Information

WATCHMAN Trial Manager

Boston Scientific

Phone: 1-800-227-3422

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place