Evaluation of the WATCHMAN Left Atrial Appendage (LAA) Cl... | NCT01182441

Evaluation of the WATCHMAN Left Atrial Appendage (LAA) Cl... | NCT01182441 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
WATCHMAN	Experimental	Subjects assigned to receive the WATCHMAN device.	Device: WATCHMAN Device
Warfarin	Active Comparator	Subjects assigned to warfarin therapy.	Drug: Warfarin

Name	Type	Description	Arm Group Labels	Other Names
WATCHMAN Device	Device	WATCHMAN Left Atrial Appendage Closure Technology	WATCHMAN

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Primary Safety Endpoint (Device Group Only)	7-Day procedure rate of death, ischemic stroke, systemic embolism and complications requiring major cardiovascular or endovascular intervention.	7-Day
Composite of Stroke, Systemic Embolism, and Death (Cardiovascular and Unknown)	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.	18 month rate
Composite of Ischemic Stroke or Systemic Embolism	Composite of ischemic stroke or systemic embolism excluding events that occurred in the first 7 days following randomization	Day 8 to 18-months

Contacts/Locations Module

Name	Affiliation	Role
David R. Holmes, M.D.	Mayo Clinic	Principal Investigator
Vivek Y. Reddy, M.D.	Icahn School of Medicine at Mount Sinai	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Mercy Gilbert Medical Center		Gilbert	Arizona	85297	United States
Arizona Heart Rhythm Research Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
35902169	Derived	Dukkipati SR, Holmes DR Jr, Doshi SK, Kar S, Singh SM, Gibson D, Price MJ, Natale A, Mansour M, Sievert H, Houle VM, Allocco DJ, Reddy VY. Impact of Peridevice Leak on 5-Year Outcomes After Left Atrial Appendage Closure. J Am Coll Cardiol. 2022 Aug 2;80(5):469-483. doi: 10.1016/j.jacc.2022.04.062.
35512918	Derived

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	WATCHMAN	Subjects assigned to receive the WATCHMAN device. WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology
FG001	Warfarin	Subjects assigned to warfarin therapy. Warfarin: Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Comment	Reasons
Patient Still in Follow-up		FG000152 subjects FG00172 subjects
Death		FG00037 subjects FG00125 subjects
Implant Attempt Unsuccessful		FG00013 subjects FG0010 subjects
Lost to Follow-up		FG0005 subjects FG0018 subjects
Withdrawal by Subject		FG0006 subjects FG00113 subjects
Implant Not Attempted		FG0004 subjects FG0010 subjects
Adverse Event		FG0002 subjects FG0010 subjects
Physician Decision		FG0001 subjects FG0011 subjects

Arm/Group Information

ID	Title	Description
BG000	WATCHMAN	Subjects assigned to receive the WATCHMAN device. WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology
BG001	Warfarin	Subjects assigned to warfarin therapy. Warfarin: Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00074.0± 7.4 BG00174.9± 7.2 BG00274.3± 7.4

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00087 BG00135 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Asian

Title	Measurements
	BG0001 BG0011 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG000269 BG001138 BG002

CHADS2 Stroke Risk Score

The CHADS2 score is used to estimate the risk of stroke in patients with non-rheumatic atrial fibrillation. To calculate the CHADS2 score, one point was assigned each for the presence of Congestive heart failure, history of Hypertension, Age 75 years or older, and Diabetes, and two points assigned for prior Stroke or TIA.

The range for this stroke scale is 0, with an annual stroke risk of 1.9%, to 6, which represents the highest risk of stroke for these patients using this scale and an annual stroke risk of 18.2% (JAMA. 285 (22): 2864-70).

Mean

Standard Deviation

scores on a scale

Title

Denominators

Categories

Title	Measurements
	BG0002.6± 1.0 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Primary Safety Endpoint (Device Group Only)

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

Posted

Count of Participants

Participants

7-Day

ID	Title	Description
OG000	WATCHMAN	Subjects assigned to receive the WATCHMAN device. WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology

Units	Counts
Participants	OG000269

Title

Denominators

Categories

Title	Measurements
	OG0006

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	Bayesian calculations were used to incorporate the data from PROTECT AF CAP Registry through a conjugate beta-binomial model. A one-sided upper 95% credible interval for the event rate was calculated based off this posterior distribution.					probability of experiencing an event	2.2			1-Sided	95		2.652					Superiority	Success for this endpoint was achieved if the probability of experiencing an event was statistically less than the performance goal, defined as 2.67%, with an upper bound of the one-sided 95% credible interval less than the performance goal.

Primary

Composite of Stroke, Systemic Embolism, and Death (Cardiovascular and Unknown)

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.

Posted

Number

Probability of events within 18 months

18 month rate

ID	Title	Description
OG000	WATCHMAN	Subjects assigned to receive the WATCHMAN device. WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology
OG001	Warfarin	Subjects assigned to warfarin therapy. Warfarin: Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0

Units	Counts
Participants

Primary

Composite of Ischemic Stroke or Systemic Embolism

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

Posted

Number

Probability of events within 18-months

Day 8 to 18-months

ID	Title	Description
OG000	WATCHMAN	Subjects assigned to receive the WATCHMAN device. WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology
OG001	Warfarin	Subjects assigned to warfarin therapy. Warfarin: Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	WATCHMAN	Subjects assigned to receive the WATCHMAN device. WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology	37	269	86	269	38	269
EG001	Warfarin	Subjects assigned to warfarin therapy. Warfarin: Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0	25	138	44	138	10	138

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
AV fistula	Vascular disorders	Systematic Assessment	EG0001 events1 affected269 at risk EG0010 events0 affected138 at risk
Anemia requiring transfusion	Blood and lymphatic system disorders	Systematic Assessment	EG0003 events3 affected269 at risk EG0010 events0 affected138 at risk
Bleeding, other	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected269 at risk EG0012 events2 affected138 at risk
Cardiac perforation	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected269 at risk EG0010 events0 affected138 at risk
Cranial bleed	General disorders	Systematic Assessment	EG0001 events1 affected269 at risk EG0010 events0 affected138 at risk
Death	General disorders	Systematic Assessment	EG00036 events36 affected269 at risk EG00124 events24 affected138 at risk
Device embolization	Injury, poisoning and procedural complications	Systematic Assessment	EG0002 events2 affected269 at risk EG0010 events0 affected138 at risk
Device thrombus	General disorders	Systematic Assessment	EG0001 events1 affected269 at risk EG0010 events0 affected138 at risk
Epistaxis	Ear and labyrinth disorders	Systematic Assessment	EG0002 events2 affected269 at risk EG0012 events2 affected138 at risk
Gastrointestinal bleeding	Gastrointestinal disorders	Systematic Assessment	EG00019 events19 affected269 at risk EG00112 events12 affected138 at risk
Hematoma	Blood and lymphatic system disorders	Systematic Assessment	EG0002 events2 affected269 at risk EG0011 events1 affected138 at risk
Hematuria	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected269 at risk EG0012 events2 affected138 at risk
Infection	Infections and infestations	Systematic Assessment	EG0003 events3 affected269 at risk EG0010 events0 affected138 at risk
Major bleeding requiring transfusion	Blood and lymphatic system disorders	Systematic Assessment	EG0006 events6 affected269 at risk EG0012 events2 affected138 at risk
Other study related	General disorders	Systematic Assessment	EG0007 events6 affected269 at risk EG0011 events1 affected138 at risk
Pericardial effusion with cardiac tamponade	Injury, poisoning and procedural complications	Systematic Assessment	EG0004 events4 affected269 at risk EG0010 events0 affected138 at risk
Pseudoaneurysm	Vascular disorders	Systematic Assessment	EG0001 events1 affected269 at risk EG0010 events0 affected138 at risk
Rectal bleeding	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected269 at risk EG0010 events0 affected138 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 events2 affected269 at risk EG0010 events0 affected138 at risk
Respiratory insufficiency	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected269 at risk EG0010 events0 affected138 at risk
Hemorrhagic stroke	Cardiac disorders	Systematic Assessment	EG0002 events2 affected269 at risk EG0013 events3 affected138 at risk
Ischemic stroke	Cardiac disorders	Systematic Assessment	EG00016 events15 affected269 at risk EG0014 events4 affected138 at risk
Subdural hematoma	Blood and lymphatic system disorders	Systematic Assessment	EG0002 events2 affected269 at risk EG0010 events0 affected138 at risk
Systemic embolism	Cardiac disorders	Systematic Assessment	EG0001 events1 affected269 at risk EG0010 events0 affected138 at risk
Transient ischemic attack	Cardiac disorders	Systematic Assessment	EG0006 events5 affected269 at risk EG0012 events2 affected138 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Anemia requiring transfusion	Blood and lymphatic system disorders	Systematic Assessment	EG0005 events4 affected269 at risk EG0010 events0 affected138 at risk
Bleeding, other	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected269 at risk EG0012 events2 affected138 at risk
Device thrombus	General disorders	Systematic Assessment	EG00016 events15 affected269 at risk EG0010 events0 affected138 at risk
Epistaxis	Ear and labyrinth disorders	Systematic Assessment	EG0005 events5 affected269 at risk EG0012 events1 affected138 at risk
Gastrointestinal bleeding	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected269 at risk EG0013 events2 affected138 at risk
Hematuria	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected269 at risk EG0013 events3 affected138 at risk
Oral bleeding	General disorders	Systematic Assessment	EG0002 events2 affected269 at risk EG0010 events0 affected138 at risk
Other study related	General disorders	Systematic Assessment	EG0002 events2 affected269 at risk EG0010 events0 affected138 at risk
Pericardial effusion, non-serious	Cardiac disorders	Systematic Assessment	EG0002 events2 affected269 at risk EG0010 events0 affected138 at risk
Pseudoaneurysm	Vascular disorders	Systematic Assessment	EG0002 events2 affected269 at risk EG0010 events0 affected138 at risk
Rectal bleeding	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected269 at risk EG0010 events0 affected138 at risk
Transient ischemic attack	Cardiac disorders	Systematic Assessment	EG0002 events2 affected269 at risk EG0012 events2 affected138 at risk

Ancestor Terms

ID	Term
D001145	Arrhythmias, Cardiac
D006331	Heart Diseases
D002318	Cardiovascular Diseases
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D002561	Cerebrovascular Disorders
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D014652	Vascular Diseases

Ancestor Terms

ID	Term
D015110	4-Hydroxycoumarins
D003374	Coumarins
D001578	Benzopyrans
D011714	Pyrans
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A Bayesian piecewise exponential model was used to model the 18-month event rates. Historical priors for each interval model were based on PROTECT AF. Hazards were modeled for 0-7 day, 7-60 day, 60-182 day, and 182+ day intervals. Event rates were estimated separately by treatment group and event type. The posterior distribution for the 18-month event rate ratio (WATCHMAN vs. Warfarin), and the corresponding equitailed 95% credible interval, were determined via Monte Carlo simulations.					Risk Ratio (RR)	1.07			2-Sided	95	0.57	1.89					Non-Inferiority	This endpoint is met if the 95% Credible Interval for the rate ratio of WATCHMAN versus Warfarin is entirely less than 1.75.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A Bayesian piecewise exponential model was used to model the 18-month event rates. Historical priors for each interval were based on PROTECT AF. Hazards were modeled for 0-7 day, 7-60 day, 60-182 day, and 182+ day intervals. Event rates were estimated separately for the WATCHMAN and Warfarin groups. The posterior distribution for the 18-month event rate ratio (WATCHMAN vs. Warfarin), and the corresponding equitailed 95% credible interval, were determined via Monte Carlo simulations.					Risk Difference (RD)	0.0053			2-Sided	95	-0.0190	0.0273					Non-Inferiority	This endpoint is met if either the 95% Credible Interval for the risk ratio < 2.0 or the 95% Credible Interval for the risk difference is < 0.0275.
OG000 OG001	A Bayesian piecewise exponential model was used to model the 18-month event rates. Historical priors for each interval were based on PROTECT AF. Hazards were modeled for 0-7 day, 7-60 day, 60-182 day, and 182+ day intervals. Event rates were estimated separately for the WATCHMAN and Warfarin groups. The posterior distribution for the 18-month event rate ratio (WATCHMAN vs. Warfarin), and the corresponding equitailed 95% credible interval, were determined via Monte Carlo simulations.					Risk Ratio (RR)	1.6			2-Sided	95	0.5	4.2					Non-Inferiority	This endpoint is met if either the 95% Credible Interval for the risk ratio < 2.0 or the 95% Credible Interval for the risk difference is < 0.0275.