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Trial record 83 of 733 for:    warfarin

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

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ClinicalTrials.gov Identifier: NCT01182441
Recruitment Status : Completed
First Posted : August 16, 2010
Results First Posted : July 26, 2018
Last Update Posted : July 26, 2018
Sponsor:
Information provided by (Responsible Party):
Boston Scientific Corporation

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Atrial Fibrillation
Stroke
Interventions Device: WATCHMAN Device
Drug: Warfarin
Enrollment 407
Recruitment Details  
Pre-assignment Details  
Arm/Group Title WATCHMAN Warfarin
Hide Arm/Group Description

Subjects assigned to receive the WATCHMAN device.

WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology

Subjects assigned to warfarin therapy.

Warfarin: Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0

Period Title: Overall Study
Started 269 138
Completed 49 19
Not Completed 220 119
Reason Not Completed
Patient Still in Follow-up             152             72
Death             37             25
Implant Attempt Unsuccessful             13             0
Lost to Follow-up             5             8
Withdrawal by Subject             6             13
Implant Not Attempted             4             0
Adverse Event             2             0
Physician Decision             1             1
Arm/Group Title WATCHMAN Warfarin Total
Hide Arm/Group Description

Subjects assigned to receive the WATCHMAN device.

WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology

Subjects assigned to warfarin therapy.

Warfarin: Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0

Total of all reporting groups
Overall Number of Baseline Participants 269 138 407
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 269 participants 138 participants 407 participants
74.0  (7.4) 74.9  (7.2) 74.3  (7.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 269 participants 138 participants 407 participants
Female
87
  32.3%
35
  25.4%
122
  30.0%
Male
182
  67.7%
103
  74.6%
285
  70.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 269 participants 138 participants 407 participants
Asian
1
   0.4%
1
   0.7%
2
   0.5%
Black/Aftrican American
6
   2.2%
1
   0.7%
7
   1.7%
Caucasian
253
  94.1%
131
  94.9%
384
  94.3%
Hispanic/Latino
6
   2.2%
5
   3.6%
11
   2.7%
Native American Indian/Alaskan Native
1
   0.4%
0
   0.0%
1
   0.2%
Other
2
   0.7%
0
   0.0%
2
   0.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 269 participants 138 participants 407 participants
269 138 407
CHADS2 Stroke Risk Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 269 participants 138 participants 407 participants
2.6  (1.0) 2.6  (1.0) 2.6  (1.0)
[1]
Measure Description:

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).

1.Primary Outcome
Title Primary Safety Endpoint (Device Group Only)
Hide Description 7-Day procedure rate of death, ischemic stroke, systemic embolism and complications requiring major cardiovascular or endovascular intervention.
Time Frame 7-Day
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title WATCHMAN
Hide Arm/Group Description:

Subjects assigned to receive the WATCHMAN device.

WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology

Overall Number of Participants Analyzed 269
Measure Type: Count of Participants
Unit of Measure: Participants
6
   2.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection WATCHMAN
Comments 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.
Type of Statistical Test Superiority
Comments 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.
Method of Estimation Estimation Parameter probability of experiencing an event
Estimated Value 2.2
Confidence Interval (1-Sided) 95%
2.652
Estimation Comments [Not Specified]
2.Primary Outcome
Title Composite of Stroke, Systemic Embolism, and Death (Cardiovascular and Unknown)
Hide Description 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.
Time Frame 18 month rate
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title WATCHMAN Warfarin
Hide Arm/Group Description:

Subjects assigned to receive the WATCHMAN device.

WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology

Subjects assigned to warfarin therapy.

Warfarin: Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0

Overall Number of Participants Analyzed 269 138
Measure Type: Number
Unit of Measure: Probability of events within 18 months
0.064 0.063
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection WATCHMAN, Warfarin
Comments 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.
Type of Statistical Test Non-Inferiority
Comments This endpoint is met if the 95% Credible Interval for the rate ratio of WATCHMAN versus Warfarin is entirely less than 1.75.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.57 to 1.89
Estimation Comments [Not Specified]
3.Primary Outcome
Title Composite of Ischemic Stroke or Systemic Embolism
Hide Description Composite of ischemic stroke or systemic embolism excluding events that occurred in the first 7 days following randomization
Time Frame Day 8 to 18-months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title WATCHMAN Warfarin
Hide Arm/Group Description:

Subjects assigned to receive the WATCHMAN device.

WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology

Subjects assigned to warfarin therapy.

Warfarin: Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0

Overall Number of Participants Analyzed 269 138
Measure Type: Number
Unit of Measure: Probability of events within 18-months
0.0253 0.0200
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection WATCHMAN, Warfarin
Comments 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.
Type of Statistical Test Non-Inferiority
Comments 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.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.0053
Confidence Interval (2-Sided) 95%
-0.0190 to 0.0273
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection WATCHMAN, Warfarin
Comments 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.
Type of Statistical Test Non-Inferiority
Comments 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.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.6
Confidence Interval (2-Sided) 95%
0.5 to 4.2
Estimation Comments [Not Specified]
Time Frame Randomization through 5-years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title WATCHMAN Warfarin
Hide Arm/Group Description

Subjects assigned to receive the WATCHMAN device.

WATCHMAN Device: WATCHMAN Left Atrial Appendage Closure Technology

Subjects assigned to warfarin therapy.

Warfarin: Warfarin dosage prescribed by study physician to adequately maintain an INR of 2.0-3.0

All-Cause Mortality
WATCHMAN Warfarin
Affected / at Risk (%) Affected / at Risk (%)
Total   37/269 (13.75%)      25/138 (18.12%)    
Show Serious Adverse Events Hide Serious Adverse Events
WATCHMAN Warfarin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   86/269 (31.97%)      44/138 (31.88%)    
Blood and lymphatic system disorders     
Anemia requiring transfusion   3/269 (1.12%)  3 0/138 (0.00%)  0
Bleeding, other   0/269 (0.00%)  0 2/138 (1.45%)  2
Hematoma   2/269 (0.74%)  2 1/138 (0.72%)  1
Major bleeding requiring transfusion   6/269 (2.23%)  6 2/138 (1.45%)  2
Subdural hematoma   2/269 (0.74%)  2 0/138 (0.00%)  0
Cardiac disorders     
Hemorrhagic stroke   2/269 (0.74%)  2 3/138 (2.17%)  3
Ischemic stroke   15/269 (5.58%)  16 4/138 (2.90%)  4
Systemic embolism   1/269 (0.37%)  1 0/138 (0.00%)  0
Transient ischemic attack   5/269 (1.86%)  6 2/138 (1.45%)  2
Ear and labyrinth disorders     
Epistaxis   2/269 (0.74%)  2 2/138 (1.45%)  2
Gastrointestinal disorders     
Gastrointestinal bleeding   19/269 (7.06%)  19 12/138 (8.70%)  12
Hematuria   1/269 (0.37%)  1 2/138 (1.45%)  2
Rectal bleeding   2/269 (0.74%)  2 0/138 (0.00%)  0
General disorders     
Cranial bleed   1/269 (0.37%)  1 0/138 (0.00%)  0
Death   36/269 (13.38%)  36 24/138 (17.39%)  24
Device thrombus   1/269 (0.37%)  1 0/138 (0.00%)  0
Other study related   6/269 (2.23%)  7 1/138 (0.72%)  1
Infections and infestations     
Infection   3/269 (1.12%)  3 0/138 (0.00%)  0
Injury, poisoning and procedural complications     
Cardiac perforation   1/269 (0.37%)  1 0/138 (0.00%)  0
Device embolization   2/269 (0.74%)  2 0/138 (0.00%)  0
Pericardial effusion with cardiac tamponade   4/269 (1.49%)  4 0/138 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Respiratory failure   2/269 (0.74%)  2 0/138 (0.00%)  0
Respiratory insufficiency   1/269 (0.37%)  1 0/138 (0.00%)  0
Vascular disorders     
AV fistula   1/269 (0.37%)  1 0/138 (0.00%)  0
Pseudoaneurysm   1/269 (0.37%)  1 0/138 (0.00%)  0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
WATCHMAN Warfarin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   38/269 (14.13%)      10/138 (7.25%)    
Blood and lymphatic system disorders     
Anemia requiring transfusion   4/269 (1.49%)  5 0/138 (0.00%)  0
Bleeding, other   0/269 (0.00%)  0 2/138 (1.45%)  2
Cardiac disorders     
Pericardial effusion, non-serious   2/269 (0.74%)  2 0/138 (0.00%)  0
Transient ischemic attack   2/269 (0.74%)  2 2/138 (1.45%)  2
Ear and labyrinth disorders     
Epistaxis   5/269 (1.86%)  5 1/138 (0.72%)  2
Gastrointestinal disorders     
Gastrointestinal bleeding   2/269 (0.74%)  2 2/138 (1.45%)  3
Hematuria   1/269 (0.37%)  1 3/138 (2.17%)  3
Rectal bleeding   2/269 (0.74%)  2 0/138 (0.00%)  0
General disorders     
Device thrombus   15/269 (5.58%)  16 0/138 (0.00%)  0
Oral bleeding   2/269 (0.74%)  2 0/138 (0.00%)  0
Other study related   2/269 (0.74%)  2 0/138 (0.00%)  0
Vascular disorders     
Pseudoaneurysm   2/269 (0.74%)  2 0/138 (0.00%)  0
Indicates events were collected by systematic assessment
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: WATCHMAN Trial Manager
Organization: Boston Scientific
Phone: 1-800-227-3422
Layout table for additonal information
Responsible Party: Boston Scientific Corporation
ClinicalTrials.gov Identifier: NCT01182441     History of Changes
Other Study ID Numbers: CT1004
First Submitted: August 12, 2010
First Posted: August 16, 2010
Results First Submitted: April 3, 2017
Results First Posted: July 26, 2018
Last Update Posted: July 26, 2018