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Dabigatran Etexilate in Extended Venous Thromboembolism (VTE) Prevention After Hip Replacement Surgery

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00168818
First received: September 12, 2005
Last updated: July 10, 2012
Last verified: July 2012
History of Changes
Results First Received: November 18, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double-Blind;   Primary Purpose: Prevention
Conditions: Thromboembolism
Arthroplasty, Replacement, Hip
Interventions: Drug: dabigatran etexilate
Drug: enoxaparin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The treatment period is from first administration of study medication, until 3 days after last administration of study medication. Treatment duration is planned for 28 - 35 days. The study period is from first administration of study medication until day 84 - 91.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Whilst 3494 patients were enrolled/randomised to treatment prior to surgery in this trial, only 3463 started treatment. Therefore, 31 patients were randomised but not treated (treatment was planned to start post surgery).

Reporting Groups
  Description
Dabigatran 220mg qd (once daily) oral
Dabigatran 150mg qd (once daily) oral
Enoxaparin 40mg qd (once daily) subcutaneous

Participant Flow for 2 periods

 Period 1:   Overall Study
    Dabigatran 220mg     Dabigatran 150mg     Enoxaparin  
STARTED     1146     1163     1154  
COMPLETED     1029     1054     1030  
NOT COMPLETED     117     109     124  
Adverse Event                 23                 29                 31  
Protocol Violation                 16                 11                 11  
Lost to Follow-up                 13                 4                 15  
Withdrawal by Subject                 43                 41                 37  
not specified                 22                 24                 30  

Period 2:   Treatment
    Dabigatran 220mg     Dabigatran 150mg     Enoxaparin  
STARTED     1146     1163     1154  
COMPLETED     1013     1012     1021  
NOT COMPLETED     133     151     133  
Adverse Event                 77                 89                 68  
Protocol Violation                 8                 11                 11  
Lost to Follow-up                 0                 2                 1  
Withdrawal by Subject                 25                 20                 22  
not specified                 23                 29                 31  



  Baseline Characteristics
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Reporting Groups
  Description
Dabigatran 220mg qd (once daily) oral
Dabigatran 150mg qd (once daily) oral
Enoxaparin 40mg qd (once daily) subcutaneous
Total Total of all reporting groups

Baseline Measures
    Dabigatran 220mg     Dabigatran 150mg     Enoxaparin     Total  
Number of Participants  
[units: participants]
 		  1146     1163     1154     3463  
Age  
[units: Years]
Mean ± Standard Deviation 		  64.6  ± 10.4     63.4  ± 11.1     63.8  ± 10.8     63.9  ± 10.8  
Gender  
[units: Participants]
 		       
Female     636     667     651     1954  
Male     510     496     503     1509  
Body Mass Index  
[units: kg/m^2]
Mean ± Standard Deviation 		  27.7  ± 4.6     27.8  ± 4.6     27.5  ± 4.3     27.7  ± 4.5  



  Outcome Measures
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1.  Primary:   Total Venous Thromboembolic Event and All-cause Mortality During Treatment Period   [ Time Frame: 28 - 35 days ]
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Measure Type Primary
Measure Title Total Venous Thromboembolic Event and All-cause Mortality During Treatment Period
Measure Description

Total Venous Thromboembolic Event (VTE) includes both proximal and distal deep vein thrombosis (DVT) (detected by routine venography), symptomatic DVT (confirmed by venous duplex, ultrasound, venography or autopsy) and pulmonary embolism (PE) (confirmed by pulmonary V-Q scintagraphy, chest x-ray, pulmonary angiography, spiral CT or autopsy).

All of these components and all deaths were centrally adjudicated by the VTE events committee, which was not aware of the treatment allocation of the patients.
Time Frame 28 - 35 days  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set (all patients who had surgery and were randomised, received treatment, had an evaluable venogram for distal and proximal Deep Vein Thrombosis, or symptomatic Deep Vein Thrombosis, Pulmonary Embolism, or had died)

Reporting Groups
  Description
Dabigatran 220mg qd (once daily) oral
Dabigatran 150mg qd (once daily) oral
Enoxaparin 40mg qd (once daily) subcutaneous

Measured Values
    Dabigatran 220mg     Dabigatran 150mg     Enoxaparin  
Number of Participants Analyzed  
[units: participants]
 		  880     874     897  
Total Venous Thromboembolic Event and All-cause Mortality During Treatment Period  
[units: Participants]
 		  53     75     60  


Statistical Analysis 1 for Total Venous Thromboembolic Event and All-cause Mortality During Treatment Period
Groups [1] Dabigatran 220mg vs. Enoxaparin
Non-Inferiority/Equivalence Test [2] Yes
Method [3] Normal approximation
P Value [4] 0.5648
Risk Difference (Percentage) [5] -0.7
95% Confidence Interval ( -2.9 to 1.6 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Risk difference versus Enoxaparin
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Non-inferiority Analysis with NI margin 7.7%
[3] Other relevant information, such as adjustments or degrees of freedom:
  Normal approximation of independent binomial distribution without stratification
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  for superiority
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Total Venous Thromboembolic Event and All-cause Mortality During Treatment Period
Groups [1] Dabigatran 150mg vs. Enoxaparin
Non-Inferiority/Equivalence Test [2] Yes
Method [3] Normal approximation
P Value [4] 0.1339
Risk Difference (Percentage) [5] 1.9
95% Confidence Interval ( -0.6 to 4.4 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Risk difference versus Enoxaparin
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Non-inferiority Analysis with NI margin 7.7%
[3] Other relevant information, such as adjustments or degrees of freedom:
  Normal approximation of independent binomial distribution without stratification
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  for superiority
[5] Other relevant estimation information:
  No text entered.



2.  Secondary:   Major Venous Thromboembolic Event and Venous Thromboembolic Event-related Mortality During Treatment Period   [ Time Frame: 28 - 35 days ]
  Show Outcome Measure 2

3.  Secondary:   Proximal Deep Vein Thrombosis During Treatment Period   [ Time Frame: 28 - 35 days ]
  Show Outcome Measure 3

4.  Secondary:   Total Deep Vein Thrombosis During Treatment Period   [ Time Frame: 28 - 35 days ]
  Show Outcome Measure 4

5.  Secondary:   Symptomatic Deep Vein Thrombosis During Treatment Period   [ Time Frame: 28 - 35 days ]
  Show Outcome Measure 5

6.  Secondary:   Pulmonary Embolism During Treatment Period   [ Time Frame: 28 - 35 days ]
  Show Outcome Measure 6

7.  Secondary:   Death During Treatment Period   [ Time Frame: 28 - 35 days ]
  Show Outcome Measure 7

8.  Secondary:   Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period   [ Time Frame: 3 months ]
  Show Outcome Measure 8

9.  Secondary:   Major Bleeding Events During Treatment Period   [ Time Frame: 28 - 35 days ]
  Show Outcome Measure 9


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim Pharmaceuticals
phone: 1-800-243-0127
e-mail: clintriage.rdg@boehringer-ingelheim.com


No publications provided by Boehringer Ingelheim Pharmaceuticals

Publications automatically indexed to this study:


Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00168818     History of Changes
Other Study ID Numbers: 1160.48, 2004-001988-21
Study First Received: September 12, 2005
Results First Received: November 18, 2010
Last Updated: July 10, 2012
Health Authority: Australia: Therapeutic Goods Administration
Austria:
Belgium: Federal Agency for Medicines and Health Products
Czech Republic: SUKL
Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency
France: Agence Francaise de Securite Sanitaire des Produits de Sante
Germany: Bundesamt fuer Strahlenschutz
Hungary:
Italy: Comitato di Bioetica IRCCS Policlinico San Matteo Viale Golgi, 19 - 27100 PAVIA
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Norway: Norwegian Medicines Agency
Poland: CEBK
South Africa: Medicines Control Council
Spain: Agencia Española de Medicamentos y Productos Santarios
Sweden: MPA