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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00657150




Registration number
NCT00657150
Ethics application status
Date submitted
27/03/2008
Date registered
14/04/2008
Date last updated
2/07/2014

Titles & IDs
Public title
Dabigatran Etexilate Compared With Enoxaparin in Prevention of Venous Thromboembolism (VTE) Following Total Hip Arthroplasty
Scientific title
A Phase III Randomised, Parallel Group, Double-blind, Active Controlled Study to Investigate the Efficacy and Safety of Orally Administered 220 mg Dabigatran Etexilate Capsules (110 mg Administered on the Day of Surgery Followed by 220 mg Once Daily) Compared to Subcutaneous 40 mg Enoxaparin Once Daily for 28-35 Days, in Prevention of Venous Thromboembolism in Patients With Primary Elective Total Hip Arthroplasty Surgery. (RE-NOVATE II)
Secondary ID [1] 0 0
2007-002630-11
Secondary ID [2] 0 0
1160.64
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Venous Thromboembolism 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Blood 0 0 0 0
Clotting disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Enoxaparin
Treatment: Drugs - Dabigatran etexilate

Experimental: Dabigatran etexilate - 220 mg once daily

Active Comparator: Enoxaparin - 40 mg once daily


Treatment: Drugs: Enoxaparin
40 mg once daily

Treatment: Drugs: Dabigatran etexilate
220 mg once daily

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Total Venous Thromboembolic Event and All-cause Mortality During Treatment Period - 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 scintigraphy, 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.
Timepoint [1] 0 0
28-35 days
Secondary outcome [1] 0 0
Number of Participants With Major Venous Thromboembolic Event and Venous Thromboembolic Event-related Mortality During Treatment Period - Major Venous Thromboembolic Event (VTE) is defined as proximal DVT and PE, as adjudicated by the VTE events committee
Timepoint [1] 0 0
28-35 days
Secondary outcome [2] 0 0
Number of Participants With Proximal Deep Vein Thrombosis During Treatment Period - Proximal Deep Vein Thrombosis as adjudicated by the VTE events committee
Timepoint [2] 0 0
28-35 days
Secondary outcome [3] 0 0
Number of Participants With Total Deep Vein Thrombosis During Treatment Period - Total Deep Vein Thrombosis as adjudicated by the VTE events committee
Timepoint [3] 0 0
28-35 days
Secondary outcome [4] 0 0
Number of Participants With Symptomatic Deep Vein Thrombosis During Treatment Period - Symptomatic Deep Vein Thrombosis, confirmed by venous duplex, ultrasound, venography or autopsy, and as adjudicated by the VTE events committee
Timepoint [4] 0 0
28-35 days
Secondary outcome [5] 0 0
Number of Participants With Pulmonary Embolism During Treatment Period - Pulmonary embolism confirmed by pulmonary V-Q scintigraphy, chest x-ray, pulmonary angiography, spiral CT or autopsy, and as adjudicated by the VTE events committee
Timepoint [5] 0 0
28-35 days
Secondary outcome [6] 0 0
Number of Participants Who Died During Treatment Period - All cause death, as adjudicated by the VTE events committee
Timepoint [6] 0 0
28-35 days
Secondary outcome [7] 0 0
Number of Participants With Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period - 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 scintigraphy, chest x-ray, pulmonary angiography, spiral CT or autopsy).
Timepoint [7] 0 0
3 months
Secondary outcome [8] 0 0
Number of Participants With Bleeding Events (Defined According to Modified McMaster Criteria) During Treatment Period - Major bleeding events were defined as
fatal
clinically overt associated with loss of haemoglobin >=20g/L in excess of what was expected
clinically overt leading to the transfusion of >=2 units packed cells or whole blood in excess of what was expected
symptomatic retroperitoneal, intracranial, intraocular or intraspinal
requiring treatment cessation
leading to re-operation
Clinically-relevant was defined as
spontaneous skin hematoma >=25 cm²
wound hematoma >=100 cm²
spontaneous nose bleed >5 min
macroscopic hematuria spontaneous or >24 hours if associated with an intervention
spontaneous rectal bleeding
gingival bleeding >5 min
any other bleeding event considered clinically relevant by the investigator
Any bleeding events were defined as major, clinically-relevant and minor bleeding events. Minor bleeding events were defined as all other bleeding events that did not fulfil the criteria from above.
Timepoint [8] 0 0
28-35 days
Secondary outcome [9] 0 0
Blood Transfusion - Number of treated and operated patients with required blood transfusion on day of surgery.
Timepoint [9] 0 0
Day 1
Secondary outcome [10] 0 0
Volume of Blood Loss - Volume of blood loss for treated and operated patients during surgery.
Timepoint [10] 0 0
Day 1
Secondary outcome [11] 0 0
Laboratory Analyses - Frequency of patients with possible clinically significant abnormalities.
Timepoint [11] 0 0
First administration to end of study

Eligibility
Key inclusion criteria
Inclusion criteria:

- Patients scheduled to undergo primary, unilateral, elective total hip arthroplasty.

- Male or female 18 years of age or older.

- Patients giving written informed consent for study participation.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Patients weighing less than 40 kg.

- History of bleeding diathesis.

- Patients who in the investigators judgement are perceived as having an excessive risk
of bleeding, for example, constitutional or acquired coagulation disorders or because
of anticipated need of quinidine, verapamil or other restricted medication during the
treatment period (see Section 4.2.2).

- Major surgery or trauma (e.g., hip fracture) within 3 months of enrolment.

- Recent unstable cardiovascular disease (in the investigators opinion) such as
uncontrolled hypertension, that is ongoing at the time of enrolment or history of
myocardial infarction within 3 months of enrolment.

- Any history of haemorrhagic stroke or any of the following intracranial pathologies:
bleeding, neoplasm, Atriovenous (AV) malformation or aneurysm.

- Ongoing treatment for Venous Thromboembolism (VTE).

- Clinically relevant bleeding (gastrointestinal, pulmonary, intraocular or urogenital
bleeding) within 6 months of enrolment.

- Gastric or duodenal ulcer within one year of enrolment.

- Liver disease expected to have any potential impact on survival (ie, hepatitis B or C,
cirrhosis). This does not include Gilberts syndrome or hepatitis A with complete
recovery.

- Active liver disease or liver disease decreasing survival (e.g, acute hepatitis,
chronic active hepatitis, cirrhosis) or Alanine Aminotransferase (ALT) >3 x ULN.

- Known severe renal insufficiency (CrCl <30 ml/min). Note: CrCl should be calculated
only if serum creatinine is elevated or renal insufficiency is suspected. See Appendix
10.1 for calculation.

- Elevated creatinine that, in the investigators opinion, contraindicates venography.

- Treatment with anticoagulants, clopidogrel, ticlopidine, abciximab, aspirin >162.5
mg/day or NSAID with t 1/2 >12 hours within 7 days prior to hip replacement surgery OR
anticipated need while the patient is receiving study medication and prior to 24 hours
after the last administration of any blinded study medication (COX-2 selective
inhibitors are allowed).

- Anticipated required use of intermittent pneumatic compression and electric
stimulation of lower limb.

- Pre-menopausal women (last menstruation within 1 year prior to signing informed
consent) who:

- Are pregnant.

- Are nursing.

- Are of child-bearing potential and are NOT practicing acceptable methods of birth
control, or do NOT plan to continue practicing an acceptable method throughout
the study. Acceptable methods of birth control include intrauterine device; oral,
implantable or injectable contraceptives and surgical sterility.

- Known allergy to radio opaque contrast media.

- History of thrombocytopenia, including heparin-induced thrombocytopenia, or a platelet
count <100,000 cells/microliter at randomisation.

- Allergy to heparins or dabigatran etexilate.

- Active malignant disease or current cytostatic treatment. Patients should be disease
free for at least 5 years.

- Participation in a clinical trial within 30 days of randomisation.

- Leg amputee.

- Known alcohol or drug abuse which would interfere with completion of the study.

- Contraindications to enoxaparin.

- Previous participation in this study.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
1160.64.2003 Boehringer Ingelheim Investigational Site - Daws Park
Recruitment hospital [2] 0 0
1160.64.2002 Boehringer Ingelheim Investigational Site - Box HIll
Recruitment hospital [3] 0 0
1160.64.2001 Boehringer Ingelheim Investigational Site - Windsor
Recruitment hospital [4] 0 0
1160.64.2004 Boehringer Ingelheim Investigational Site - Nedlands
Recruitment postcode(s) [1] 0 0
- Daws Park
Recruitment postcode(s) [2] 0 0
- Box HIll
Recruitment postcode(s) [3] 0 0
- Windsor
Recruitment postcode(s) [4] 0 0
- Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Montana
Country [6] 0 0
United States of America
State/province [6] 0 0
South Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
Austria
State/province [9] 0 0
Graz
Country [10] 0 0
Austria
State/province [10] 0 0
Linz
Country [11] 0 0
Austria
State/province [11] 0 0
Wels
Country [12] 0 0
Austria
State/province [12] 0 0
Wien
Country [13] 0 0
Belgium
State/province [13] 0 0
Brussel
Country [14] 0 0
Belgium
State/province [14] 0 0
Deurne
Country [15] 0 0
Belgium
State/province [15] 0 0
Lanaken
Country [16] 0 0
Belgium
State/province [16] 0 0
Leuven
Country [17] 0 0
Canada
State/province [17] 0 0
Alberta
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Czech Republic
State/province [19] 0 0
Chomutov
Country [20] 0 0
Czech Republic
State/province [20] 0 0
Jihlava
Country [21] 0 0
Czech Republic
State/province [21] 0 0
Kolin
Country [22] 0 0
Czech Republic
State/province [22] 0 0
Plzen
Country [23] 0 0
Czech Republic
State/province [23] 0 0
Prague 8
Country [24] 0 0
Denmark
State/province [24] 0 0
Frederiksberg
Country [25] 0 0
Denmark
State/province [25] 0 0
Herlev
Country [26] 0 0
Denmark
State/province [26] 0 0
Hørsholm
Country [27] 0 0
Denmark
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Silkeborg
Country [28] 0 0
Finland
State/province [28] 0 0
Jyväskylä
Country [29] 0 0
Finland
State/province [29] 0 0
Oulu
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Finland
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Tampere
Country [31] 0 0
Germany
State/province [31] 0 0
Garmisch-Partenkirchen
Country [32] 0 0
Germany
State/province [32] 0 0
Mainz
Country [33] 0 0
Germany
State/province [33] 0 0
Markgröningen
Country [34] 0 0
Germany
State/province [34] 0 0
Rheinfelden
Country [35] 0 0
Hungary
State/province [35] 0 0
Gyula
Country [36] 0 0
Hungary
State/province [36] 0 0
Kecskemét
Country [37] 0 0
Hungary
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Szeged
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Hungary
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Székesfehérvár
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India
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Ahmedabad
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India
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Andhra Pradesh
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India
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Andhra Predesh
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India
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Bangalore
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India
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Baroda
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India
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Mangalore
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India
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Mohali
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India
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New Delhi
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India
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Pune
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India
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Ramdaspeth Nagpur
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India
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Secunderabad
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India
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Vadodara
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Bologna
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Italy
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Parma
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Italy
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Pavia
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Italy
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Reggio Emilia
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Italy
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Roma
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Italy
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Torino
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Netherlands
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Amsterdam
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Netherlands
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Hilversum
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Netherlands
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Hoofddorp
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Leiden
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Sittard
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Netherlands
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Zwolle
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New Zealand
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Takapuna Auckland
Country [64] 0 0
Norway
State/province [64] 0 0
Bodø
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Norway
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Elverum
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Norway
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Lillehammer
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Norway
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Tynset
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Norway
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Ålesund
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Poland
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Krakow
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Poland
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Lodz
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Poland
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Piekary Slaskie
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Warsaw
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South Africa
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Bryanston
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South Africa
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Cape Western Province
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South Africa
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Plumstead
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Spain
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Alcorcón (Madrid)
Country [77] 0 0
Spain
State/province [77] 0 0
Barcelona
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Spain
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Fuenlabrada
Country [79] 0 0
Spain
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Madrid
Country [80] 0 0
Spain
State/province [80] 0 0
Valencia
Country [81] 0 0
Sweden
State/province [81] 0 0
Göteborg
Country [82] 0 0
Sweden
State/province [82] 0 0
Halmstad
Country [83] 0 0
Sweden
State/province [83] 0 0
Hässleholm
Country [84] 0 0
Sweden
State/province [84] 0 0
Kalmar
Country [85] 0 0
Sweden
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Kungälv
Country [86] 0 0
Sweden
State/province [86] 0 0
Lidköping
Country [87] 0 0
Sweden
State/province [87] 0 0
Motala
Country [88] 0 0
Sweden
State/province [88] 0 0
Stockholm
Country [89] 0 0
Sweden
State/province [89] 0 0
Uppsala
Country [90] 0 0
Sweden
State/province [90] 0 0
Varberg

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of the trial is to demonstrate non-inferiority of 220 mg oral
dabigatran etexilate compared to 40 mg subcutaneous enoxaparin administered once daily.
Safety and efficacy will be compared between the treatment groups.
Trial website
https://clinicaltrials.gov/show/NCT00657150
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Boehringer Ingelheim
Address 0 0
Boehringer Ingelheim
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications