Clinical trial NCT00168818: Dabigatran Etexilate in Extended Venous Thromboembolism (VTE) Prevention After Hip Replacement Surgery
Official title: A Phase III Randomised, Parallel Group, Double-blind, Active Controlled Study to Investigate the Efficacy and Safety of Two Different Dose Regimens of Orally Administered Dabigatran Etexilate Capsules [150 or 220 mg Once Daily Starting With Half Dose (75 or 110 mg) on the Day of Surgery] Compared to Subcutaneous Enoxaparin 40 mg Once Daily for 28-35 Days, in Prevention of Venous Thromboembolism in Patients With Primary Elective Total Hip Replacement Surgery. RE-NOVATE (Extended Thromboembolism Prevention After Hip Surgery)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Thromboembolism
Arthroplasty, Replacement, Hip
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2005-09-15
Enrollment: 3494
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The objective of this study is to determine the comparative efficacy and safety of two oral regimens of dabigatran etexilate, compared to a standard subcutaneous regimen of enoxaparin, in prevention of venous thromboembolism in patients with primary elective total hip replacement surgery.


Eligibility criteria: Inclusion criteria

Inclusion criteria (selected):

* Patients (18 years or older) scheduled to undergo a primary, unilateral, elective total hip replacement
* Written Informed Consent

Exclusion criteria

Exclusion criteria (selected):

* Patients with an excessive risk of bleeding, for example because of history of bleeding diathesis major surgery or trauma within the last 3 months history of haemorrhagic stroke or any of the following intracranial pathologies: bleeding, neoplasm, AV malformation or aneurysm clinically relevant bleeding or gastric / duodenal ulcer within the last 6 months treatment with anticoagulants within 7 days prior to joint replacement surgery or anticipated need during the study treatment period thrombocytopenia.
* Active malignant disease or current cytostatic treatment
* Known severe renal insufficiency
* Liver disease expected to have any potential impact on survival, or elevated AST or ALT \> 2x upper limit of normal
* Recent unstable cardiovascular disease or history of myocardial infarction within the last 3 months
* Pre-menopausal women who are pregnant or nursing, or are of child-bearing potential and are not practising or do not plan to continue practising acceptable methods of birth control
* Allergy to radio opaque contrast media or iodine, heparins (incl. heparin induced thrombocytopenia) or dabigatran
* Contraindications to enoxaparin
* Participation in a clinical trial during the last 30 days

Primary outcomes:
measure: Total Venous Thromboembolic Event and All-cause Mortality During Treatment Period
timeFrame: First administration until 31-38 days
Secondary outcomes:
measure: Major Venous Thromboembolic Event and Venous Thromboembolic Event-related Mortality During Treatment Period
timeFrame: First administration until 31-38 days
measure: Proximal Deep Vein Thrombosis During Treatment Period
timeFrame: First administration until 31-38 days
measure: Total Deep Vein Thrombosis During Treatment Period
timeFrame: First administration until 31-38 days
measure: Symptomatic Deep Vein Thrombosis During Treatment Period
timeFrame: First administration until 31-38 days
measure: Pulmonary Embolism During Treatment Period
timeFrame: First administration until 31-38 days
measure: Death During Treatment Period
timeFrame: First administration until 31-38 days
measure: Total Venous Thromboembolic Event (VTE) and All-cause Mortality During the Follow-up Period
timeFrame: end of treatment to day 91±7
measure: Number of Participants With Bleeding Events (Defined According to Modified McMaster Criteria) During Treatment Period
timeFrame: First administration until 31-38 days
measure: Blood Transfusion
timeFrame: Day 1
measure: Volume of Blood Loss
timeFrame: Day 1
measure: Laboratory Analyses
timeFrame: First administration to end of study
Other outcomes:
Locations:
city: Garren
country: Australia
facility: 1160.48.06108 Canberra Hospital
state: Australian Capital Territory
city: Kogarah
country: Australia
facility: 1160.48.06106 St George Public Hospital
state: New South Wales
city: Lismore
country: Australia
facility: 1160.48.06110 Suite 13 level 4
state: New South Wales
city: Bedford Park
country: Australia
facility: 1160.48.06105 Flinders Medical Centre
state: South Australia
city: Box Hill
country: Australia
facility: 1160.48.06104 Ecru
state: Victoria
city: Clayton
country: Australia
facility: 1160.48.06102 Monash Medical Centre
state: Victoria
city: Malvern
country: Australia
facility: 1160.48.06101 Emeritus Research
state: Victoria
city: Ringwood East
country: Australia
facility: 1160.48.06103 Maroondah Hospital
state: Victoria
city: Windsor
country: Australia
facility: 1160.48.06113
state: Victoria
city: Perth
country: Australia
facility: 1160.48.06111 Haemophillia & Thrombosis Service
state: Western Australia
city: Linz
country: Austria
facility: 1160.48.04304 Boehringer Ingelheim Investigational Site
city: Wels
country: Austria
facility: 1160.48.04303 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 1160.48.04302 Boehringer Ingelheim Investigational Site
city: Wr. Neustadt
country: Austria
facility: 1160.48.04301 Boehringer Ingelheim Investigational Site
city: Brussels
country: Belgium
facility: 1160.48.03207 UVC Brugmann
city: Gent
country: Belgium
facility: 1160.48.03206 Campus Sint-Lucas
city: Gent
country: Belgium
facility: 1160.48.03208 UZ Gent
city: Hasselt
country: Belgium
facility: 1160.48.03202 Boehringer Ingelheim Investigational Site
city: Herentals
country: Belgium
facility: 1160.48.03203 AZ Sint Elisabeth
city: Lanaken
country: Belgium
facility: 1160.48.03205 Ziekenhuis Oost-Limburg
city: Leuven
country: Belgium
facility: 1160.48.03201 UZ Gasthuisberg
city: Brno-Bohunice
country: Czech Republic
facility: 1160.48.42004 Boehringer Ingelheim Investigational Site
city: Chomutov
country: Czech Republic
facility: 1160.48.42010 Boehringer Ingelheim Investigational Site
city: Havlickuv Brod
country: Czech Republic
facility: 1160.48.42009 Boehringer Ingelheim Investigational Site
city: Jihlava
country: Czech Republic
facility: 1160.48.42008 Boehringer Ingelheim Investigational Site
city: Kladno
country: Czech Republic
facility: 1160.48.42002 Boehringer Ingelheim Investigational Site
city: Kolin
country: Czech Republic
facility: 1160.48.42006 Boehringer Ingelheim Investigational Site
city: Ostrava
country: Czech Republic
facility: 1160.48.42003 Boehringer Ingelheim Investigational Site
city: Plzen
country: Czech Republic
facility: 1160.48.42001 Boehringer Ingelheim Investigational Site
city: Pradubice
country: Czech Republic
facility: 1160.48.42007 Boehringer Ingelheim Investigational Site
city: Prague 8
country: Czech Republic
facility: 1160.48.42005 Boehringer Ingelheim Investigational Site
city: Hellerup
country: Denmark
facility: 1160.48.04571 Boehringer Ingelheim Investigational Site
city: Hørsholm
country: Denmark
facility: 1160.48.04570 Boehringer Ingelheim Investigational Site
city: København NV
country: Denmark
facility: 1160.48.04573 Boehringer Ingelheim Investigational Site
city: København S
country: Denmark
facility: 1160.48.04574 Boehringer Ingelheim Investigational Site
city: Silkeborg
country: Denmark
facility: 1160.48.04575 Boehringer Ingelheim Investigational Site
city: Helsinki
country: Finland
facility: 1160.48.35803 Boehringer Ingelheim Investigational Site
city: Jyväskylä
country: Finland
facility: 1160.48.35802 Boehringer Ingelheim Investigational Site
city: Oulu
country: Finland
facility: 1160.48.35801 Boehringer Ingelheim Investigational Site
city: Seinäjoki
country: Finland
facility: 1160.48.35804 Boehringer Ingelheim Investigational Site
city: Tampere
country: Finland
facility: 1160.48.35805 Boehringer Ingelheim Investigational Site
city: Amiens cedex 1
country: France
facility: 1160.48.03304 Boehringer Ingelheim Investigational Site
city: Roubaix cedex
country: France
facility: 1160.48.03303 Boehringer Ingelheim Investigational Site
city: Soyaux
country: France
facility: 1160.48.03302 Boehringer Ingelheim Investigational Site
city: Strasbourg
country: France
facility: 1160.48.03308 Boehringer Ingelheim Investigational Site
city: Bad Mergentheim
country: Germany
facility: 1160.48.04906 Caritaskrankenhaus
city: Erlangen
country: Germany
facility: 1160.48.04910 F.-A.-Universität Erlangen-Nürnberg
city: Frankfurt
country: Germany
facility: 1160.48.04904 Orthopädische Universitätsklinik
city: Garmisch-Partenkirchen
country: Germany
facility: 1160.48.04902 Klinikum Garmisch-Partenkirchen
city: Kamp-Lintfort
country: Germany
facility: 1160.48.04914 St. Bernhard-Hospital
city: Mainz
country: Germany
facility: 1160.48.04907 Johannes Gutenberg-Universität Mainz
city: Markgröningen
country: Germany
facility: 1160.48.04912 Orthopädische Klinik Markgröningen gGmbH
city: Rheinfelden
country: Germany
facility: 1160.48.04901 Kreiskrankenhaus
city: Schwandorf
country: Germany
facility: 1160.48.04915 Orthopädische Klinik Lindenlohe
city: Sommerfeld
country: Germany
facility: 1160.48.04903 Hellmuth-Ulrici-Kliniken
city: Wiesbaden
country: Germany
facility: 1160.48.04905 Aukammklinik
city: Budapest
country: Hungary
facility: 1160.48.03603 Boehringer Ingelheim Investigational Site
city: Budapest
country: Hungary
facility: 1160.48.03606 Boehringer Ingelheim Investigational Site
city: Békéscsaba
country: Hungary
facility: 1160.48.03607 Boehringer Ingelheim Investigational Site
city: Gyula
country: Hungary
facility: 1160.48.03601 Boehringer Ingelheim Investigational Site
city: Kecskemét
country: Hungary
facility: 1160.48.03604 Boehringer Ingelheim Investigational Site
city: Szeged
country: Hungary
facility: 1160.48.03602 Boehringer Ingelheim Investigational Site
city: Székesfehérvár
country: Hungary
facility: 1160.48.03605 Boehringer Ingelheim Investigational Site
city: Bergamo
country: Italy
facility: 1160.48.03903 Boehringer Ingelheim Investigational Site
city: Bologna
country: Italy
facility: 1160.48.03904 Boehringer Ingelheim Investigational Site
city: Milano
country: Italy
facility: 1160.48.03902 Boehringer Ingelheim Investigational Site
city: Pavia
country: Italy
facility: 1160.48.03901 Boehringer Ingelheim Investigational Site
city: Amsterdam
country: Netherlands
facility: 1160.48.03102 Boehringer Ingelheim Investigational Site
city: Heemstede
country: Netherlands
facility: 1160.48.03101 Boehringer Ingelheim Investigational Site
city: Helmond
country: Netherlands
facility: 1160.48.03107 Boehringer Ingelheim Investigational Site
city: Hilversum
country: Netherlands
facility: 1160.48.03103 Boehringer Ingelheim Investigational Site
city: Nijmegen
country: Netherlands
facility: 1160.48.03104 Boehringer Ingelheim Investigational Site
city: Sittard
country: Netherlands
facility: 1160.48.03105 Boehringer Ingelheim Investigational Site
city: Bodø
country: Norway
facility: 1160.48.04701 Boehringer Ingelheim Investigational Site
city: Bærum Postterminal
country: Norway
facility: 1160.48.04704 Boehringer Ingelheim Investigational Site
city: Bærum Postterminal
country: Norway
facility: 1160.48.04707 Boehringer Ingelheim Investigational Site
city: Elverum
country: Norway
facility: 1160.48.04706 Boehringer Ingelheim Investigational Site
city: Skien
country: Norway
facility: 1160.48.04702 Boehringer Ingelheim Investigational Site
city: Ålesund
country: Norway
facility: 1160.48.04703 Boehringer Ingelheim Investigational Site
city: Bialystok
country: Poland
facility: 1160.48.04810 Boehringer Ingelheim Investigational Site
city: Kielce
country: Poland
facility: 1160.48.04804 Boehringer Ingelheim Investigational Site
city: Krakow
country: Poland
facility: 1160.48.04806 Boehringer Ingelheim Investigational Site
city: Krakow
country: Poland
facility: 1160.48.04807 Boehringer Ingelheim Investigational Site
city: Krakow
country: Poland
facility: 1160.48.04812 Boehringer Ingelheim Investigational Site
city: Lodz
country: Poland
facility: 1160.48.04820 Boehringer Ingelheim Investigational Site
city: Mielec
country: Poland
facility: 1160.48.04814 Boehringer Ingelheim Investigational Site
city: Piekary Slaskie
country: Poland
facility: 1160.48.04808 Boehringer Ingelheim Investigational Site
city: Rzeszow
country: Poland
facility: 1160.48.04817 Boehringer Ingelheim Investigational Site
city: Warsaw
country: Poland
facility: 1160.48.04801 Boehringer Ingelheim Investigational Site
city: Warsaw
country: Poland
facility: 1160.48.04802 Boehringer Ingelheim Investigational Site
city: Warsaw
country: Poland
facility: 1160.48.04803 Boehringer Ingelheim Investigational Site
city: Bryanston
country: South Africa
facility: 1160.48.02701 Boehringer Ingelheim Investigational Site
city: Johannesburg
country: South Africa
facility: 1160.48.02704 Boehringer Ingelheim Investigational Site
city: Randburg
country: South Africa
facility: 1160.48.02703 Boehringer Ingelheim Investigational Site
city: Sandton
country: South Africa
facility: 1160.48.02702 Boehringer Ingelheim Investigational Site
city: Alcorcón (Madrid)
country: Spain
facility: 1160.48.03405 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1160.48.03403 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1160.48.03411 Boehringer Ingelheim Investigational Site
city: Hospitalet (Barcelona)
country: Spain
facility: 1160.48.03407 Boehringer Ingelheim Investigational Site
city: Jaén
country: Spain
facility: 1160.48.03409 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1160.48.03401 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1160.48.03402 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1160.48.03404 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1160.48.03406 Boehringer Ingelheim Investigational Site
city: Móstoles (Madrid)
country: Spain
facility: 1160.48.03408 Boehringer Ingelheim Investigational Site
city: Valencia
country: Spain
facility: 1160.48.03410 Boehringer Ingelheim Investigational Site
city: Falköping
country: Sweden
facility: 1160.48.04602 Boehringer Ingelheim Investigational Site
city: Göteborg
country: Sweden
facility: 1160.48.04601 Boehringer Ingelheim Investigational Site
city: Halmstad
country: Sweden
facility: 1160.48.04607 Boehringer Ingelheim Investigational Site
city: Kalmar
country: Sweden
facility: 1160.48.04606 Boehringer Ingelheim Investigational Site
city: Kungälv
country: Sweden
facility: 1160.48.04603 Boehringer Ingelheim Investigational Site
city: Lidköping
country: Sweden
facility: 1160.48.04608 Boehringer Ingelheim Investigational Site
city: Linköping
country: Sweden
facility: 1160.48.04605 Boehringer Ingelheim Investigational Site
city: Mölndal
country: Sweden
facility: 1160.48.04604 Boehringer Ingelheim Investigational Site
city: Stockholm
country: Sweden
facility: 1160.48.04610 Boehringer Ingelheim Investigational Site
city: Varberg
country: Sweden
facility: 1160.48.04609 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Eriksson BI, Dahl OE, Rosencher N, Clemens A, Hantel S, Feuring M, Kreuzer J, Huo M, Friedman RJ. Oral dabigatran etexilate versus enoxaparin for venous thromboembolism prevention after total hip arthroplasty: pooled analysis of two phase 3 randomized trials. Thromb J. 2015 Nov 17;13:36. doi: 10.1186/s12959-015-0067-8. eCollection 2015.
citation: Eriksson BI, Dahl OE, Rosencher N, Clemens A, Hantel S, Kurth AA. Efficacy of delayed thromboprophylaxis with dabigatran: pooled analysis. Thromb Res. 2012 Dec;130(6):871-6. doi: 10.1016/j.thromres.2012.08.315. Epub 2012 Sep 17.
citation: Rosencher N, Noack H, Feuring M, Clemens A, Friedman RJ, Eriksson BI. Type of anaesthesia and the safety and efficacy of thromboprophylaxis with enoxaparin or dabigatran etexilate in major orthopaedic surgery: pooled analysis of three randomized controlled trials. Thromb J. 2012 Jun 18;10(1):9. doi: 10.1186/1477-9560-10-9.
citation: Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, Prins MH, Hettiarachchi R, Hantel S, Schnee J, Buller HR; RE-NOVATE Study Group. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet. 2007 Sep 15;370(9591):949-56. doi: 10.1016/S0140-6736(07)61445-7.