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

Thromboembolism Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00168818
• Other study ID #: 1160.48
• Secondary ID: 2004-001988-21
• Status: Completed
• Phase: Phase 3
• First received: September 12, 2005
• Last updated: May 8, 2014
• Start date: November 2004

Study information

• Verified date: February 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Therapeutic Goods AdministrationAustria:Belgium: Federal Agency for Medicines and Health Products, FAMHPCzech Republic: SUKLDenmark: Danish Medicines AgencyFinland: Finnish Medicines AgencyFrance: Agence Francaise de Securite Sanitaire des Produits de SanteGermany: Bundesamt fuer StrahlenschutzHungary:Italy: Comitato di Bioetica IRCCS Policlinico San Matteo Viale Golgi, 19 - 27100 PAVIANetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Norway: Norwegian Medicines AgencyPoland: CEBKSouth Africa: Medicines Control CouncilSpain: Agencia Española de Medicamentos y Productos SantariosSweden: MPA
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3494
• Est. primary completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Arthroplasty, Replacement, Hip
• Thromboembolism
• Venous Thromboembolism

Intervention

Drug:
• dabigatran etexilate
daily dose 150 mg once daily, half a dose on the day of surgery
• dabigatran etexilate
daily dose 150 mg once daily, half a dose on the day of surgery
• enoxaparin
40 mg once daily

Locations

Country	Name	City	State
Australia	1160.48.06105 Flinders Medical Centre	Bedford Park	South Australia
Australia	1160.48.06104 Ecru	Box Hill	Victoria
Australia	1160.48.06102 Monash Medical Centre	Clayton	Victoria
Australia	1160.48.06108 Canberra Hospital	Garren	Australian Capital Territory
Australia	1160.48.06106 St George Public Hospital	Kogarah	New South Wales
Australia	1160.48.06110 Suite 13 level 4	Lismore	New South Wales
Australia	1160.48.06101 Emeritus Research	Malvern	Victoria
Australia	1160.48.06111 Haemophillia & Thrombosis Service	Perth	Western Australia
Australia	1160.48.06103 Maroondah Hospital	Ringwood East	Victoria
Australia	1160.48.06113	Windsor	Victoria
Austria	1160.48.04304 Boehringer Ingelheim Investigational Site	Linz
Austria	1160.48.04303 Boehringer Ingelheim Investigational Site	Wels
Austria	1160.48.04302 Boehringer Ingelheim Investigational Site	Wien
Austria	1160.48.04301 Boehringer Ingelheim Investigational Site	Wr. Neustadt
Belgium	1160.48.03207 UVC Brugmann	Brussels
Belgium	1160.48.03206 Campus Sint-Lucas	Gent
Belgium	1160.48.03208 UZ Gent	Gent
Belgium	1160.48.03202 Boehringer Ingelheim Investigational Site	Hasselt
Belgium	1160.48.03203 AZ Sint Elisabeth	Herentals
Belgium	1160.48.03205 Ziekenhuis Oost-Limburg	Lanaken
Belgium	1160.48.03201 UZ Gasthuisberg	Leuven
Czech Republic	1160.48.42004 Boehringer Ingelheim Investigational Site	Brno-Bohunice
Czech Republic	1160.48.42010 Boehringer Ingelheim Investigational Site	Chomutov
Czech Republic	1160.48.42009 Boehringer Ingelheim Investigational Site	Havlickuv Brod
Czech Republic	1160.48.42008 Boehringer Ingelheim Investigational Site	Jihlava
Czech Republic	1160.48.42002 Boehringer Ingelheim Investigational Site	Kladno
Czech Republic	1160.48.42006 Boehringer Ingelheim Investigational Site	Kolin
Czech Republic	1160.48.42003 Boehringer Ingelheim Investigational Site	Ostrava
Czech Republic	1160.48.42001 Boehringer Ingelheim Investigational Site	Plzen
Czech Republic	1160.48.42007 Boehringer Ingelheim Investigational Site	Pradubice
Czech Republic	1160.48.42005 Boehringer Ingelheim Investigational Site	Prague 8
Denmark	1160.48.04571 Boehringer Ingelheim Investigational Site	Hellerup
Denmark	1160.48.04570 Boehringer Ingelheim Investigational Site	Hørsholm
Denmark	1160.48.04573 Boehringer Ingelheim Investigational Site	København NV
Denmark	1160.48.04574 Boehringer Ingelheim Investigational Site	København S
Denmark	1160.48.04575 Boehringer Ingelheim Investigational Site	Silkeborg
Finland	1160.48.35803 Boehringer Ingelheim Investigational Site	Helsinki
Finland	1160.48.35802 Boehringer Ingelheim Investigational Site	Jyväskylä
Finland	1160.48.35801 Boehringer Ingelheim Investigational Site	Oulu
Finland	1160.48.35804 Boehringer Ingelheim Investigational Site	Seinäjoki
Finland	1160.48.35805 Boehringer Ingelheim Investigational Site	Tampere
France	1160.48.03304 Boehringer Ingelheim Investigational Site	Amiens cedex 1
France	1160.48.03303 Boehringer Ingelheim Investigational Site	Roubaix cedex
France	1160.48.03302 Boehringer Ingelheim Investigational Site	Soyaux
France	1160.48.03308 Boehringer Ingelheim Investigational Site	Strasbourg
Germany	1160.48.04906 Caritaskrankenhaus	Bad Mergentheim
Germany	1160.48.04910 F.-A.-Universität Erlangen-Nürnberg	Erlangen
Germany	1160.48.04904 Orthopädische Universitätsklinik	Frankfurt
Germany	1160.48.04902 Klinikum Garmisch-Partenkirchen	Garmisch-Partenkirchen
Germany	1160.48.04914 St. Bernhard-Hospital	Kamp-Lintfort
Germany	1160.48.04907 Johannes Gutenberg-Universität Mainz	Mainz
Germany	1160.48.04912 Orthopädische Klinik Markgröningen gGmbH	Markgröningen
Germany	1160.48.04901 Kreiskrankenhaus	Rheinfelden
Germany	1160.48.04915 Orthopädische Klinik Lindenlohe	Schwandorf
Germany	1160.48.04903 Hellmuth-Ulrici-Kliniken	Sommerfeld
Germany	1160.48.04905 Aukammklinik	Wiesbaden
Hungary	1160.48.03607 Boehringer Ingelheim Investigational Site	Békéscsaba
Hungary	1160.48.03603 Boehringer Ingelheim Investigational Site	Budapest
Hungary	1160.48.03606 Boehringer Ingelheim Investigational Site	Budapest
Hungary	1160.48.03601 Boehringer Ingelheim Investigational Site	Gyula
Hungary	1160.48.03604 Boehringer Ingelheim Investigational Site	Kecskemét
Hungary	1160.48.03602 Boehringer Ingelheim Investigational Site	Szeged
Hungary	1160.48.03605 Boehringer Ingelheim Investigational Site	Székesfehérvár
Italy	1160.48.03903 Boehringer Ingelheim Investigational Site	Bergamo
Italy	1160.48.03904 Boehringer Ingelheim Investigational Site	Bologna
Italy	1160.48.03902 Boehringer Ingelheim Investigational Site	Milano
Italy	1160.48.03901 Boehringer Ingelheim Investigational Site	Pavia
Netherlands	1160.48.03102 Boehringer Ingelheim Investigational Site	Amsterdam
Netherlands	1160.48.03101 Boehringer Ingelheim Investigational Site	Heemstede
Netherlands	1160.48.03107 Boehringer Ingelheim Investigational Site	Helmond
Netherlands	1160.48.03103 Boehringer Ingelheim Investigational Site	Hilversum
Netherlands	1160.48.03104 Boehringer Ingelheim Investigational Site	Nijmegen
Netherlands	1160.48.03105 Boehringer Ingelheim Investigational Site	Sittard
Norway	1160.48.04703 Boehringer Ingelheim Investigational Site	Ålesund
Norway	1160.48.04704 Boehringer Ingelheim Investigational Site	Bærum Postterminal
Norway	1160.48.04707 Boehringer Ingelheim Investigational Site	Bærum Postterminal
Norway	1160.48.04701 Boehringer Ingelheim Investigational Site	Bodø
Norway	1160.48.04706 Boehringer Ingelheim Investigational Site	Elverum
Norway	1160.48.04702 Boehringer Ingelheim Investigational Site	Skien
Poland	1160.48.04810 Boehringer Ingelheim Investigational Site	Bialystok
Poland	1160.48.04804 Boehringer Ingelheim Investigational Site	Kielce
Poland	1160.48.04806 Boehringer Ingelheim Investigational Site	Krakow
Poland	1160.48.04807 Boehringer Ingelheim Investigational Site	Krakow
Poland	1160.48.04812 Boehringer Ingelheim Investigational Site	Krakow
Poland	1160.48.04820 Boehringer Ingelheim Investigational Site	Lodz
Poland	1160.48.04814 Boehringer Ingelheim Investigational Site	Mielec
Poland	1160.48.04808 Boehringer Ingelheim Investigational Site	Piekary Slaskie
Poland	1160.48.04817 Boehringer Ingelheim Investigational Site	Rzeszow
Poland	1160.48.04801 Boehringer Ingelheim Investigational Site	Warsaw
Poland	1160.48.04802 Boehringer Ingelheim Investigational Site	Warsaw
Poland	1160.48.04803 Boehringer Ingelheim Investigational Site	Warsaw
South Africa	1160.48.02701 Boehringer Ingelheim Investigational Site	Bryanston
South Africa	1160.48.02704 Boehringer Ingelheim Investigational Site	Johannesburg
South Africa	1160.48.02703 Boehringer Ingelheim Investigational Site	Randburg
South Africa	1160.48.02702 Boehringer Ingelheim Investigational Site	Sandton
Spain	1160.48.03405 Boehringer Ingelheim Investigational Site	Alcorcón (Madrid)
Spain	1160.48.03403 Boehringer Ingelheim Investigational Site	Barcelona
Spain	1160.48.03411 Boehringer Ingelheim Investigational Site	Barcelona
Spain	1160.48.03407 Boehringer Ingelheim Investigational Site	Hospitalet (Barcelona)
Spain	1160.48.03409 Boehringer Ingelheim Investigational Site	Jaén
Spain	1160.48.03401 Boehringer Ingelheim Investigational Site	Madrid
Spain	1160.48.03402 Boehringer Ingelheim Investigational Site	Madrid
Spain	1160.48.03404 Boehringer Ingelheim Investigational Site	Madrid
Spain	1160.48.03406 Boehringer Ingelheim Investigational Site	Madrid
Spain	1160.48.03408 Boehringer Ingelheim Investigational Site	Móstoles (Madrid)
Spain	1160.48.03410 Boehringer Ingelheim Investigational Site	Valencia
Sweden	1160.48.04602 Boehringer Ingelheim Investigational Site	Falköping
Sweden	1160.48.04601 Boehringer Ingelheim Investigational Site	Göteborg
Sweden	1160.48.04607 Boehringer Ingelheim Investigational Site	Halmstad
Sweden	1160.48.04606 Boehringer Ingelheim Investigational Site	Kalmar
Sweden	1160.48.04603 Boehringer Ingelheim Investigational Site	Kungälv
Sweden	1160.48.04608 Boehringer Ingelheim Investigational Site	Lidköping
Sweden	1160.48.04605 Boehringer Ingelheim Investigational Site	Linköping
Sweden	1160.48.04604 Boehringer Ingelheim Investigational Site	Mölndal
Sweden	1160.48.04610 Boehringer Ingelheim Investigational Site	Stockholm
Sweden	1160.48.04609 Boehringer Ingelheim Investigational Site	Varberg

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  Czech Republic,  Denmark,  Finland,  France,  Germany,  Hungary,  Italy,  Netherlands,  Norway,  Poland,  South Africa,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 bilateral venography), symptomatic DVT (confirmed by venous compression 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.	First administration until 31-38 days	No
Secondary	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	First administration until 31-38 days	No
Secondary	Proximal Deep Vein Thrombosis During Treatment Period	Proximal Deep Vein Thrombosis as adjudicated by the VTE events committee	First administration until 31-38 days	No
Secondary	Total Deep Vein Thrombosis During Treatment Period	Total Deep Vein Thrombosis as adjudicated by the VTE events committee	First administration until 31-38 days	No
Secondary	Symptomatic Deep Vein Thrombosis During Treatment Period	Symptomatic Deep Vein Thrombosis, confirmed by venous compression ultrasound, venography or autopsy, and as adjudicated by the VTE events committee	First administration until 31-38 days	No
Secondary	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	First administration until 31-38 days	No
Secondary	Death During Treatment Period	All cause death, as adjudicated by the VTE events committee	First administration until 31-38 days	No
Secondary	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 bilateral venography), symptomatic DVT (confirmed by venous compression ultrasound, venography or autopsy) and pulmonary embolism (PE) (confirmed by pulmonary V-Q scintigraphy, chest x-ray, pulmonary angiography, spiral CT or autopsy).	end of treatment to day 91±7	No
Secondary	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 greater than or equal to 25 cm²; wound hematoma greater than or equal to 100 cm²; spontaneous nose bleed lasting longer than 5 min; macroscopic hematuria spontaneous or lasting longer than 24 hours if associated with an intervention; spontaneous rectal bleeding (more than a spot on toilet paper); gingival bleeding lasting longer than 5 min; any other bleeding event considered clinically relevant by the investigator; Minor bleeding events were defined as all other bleeding events that did not fulfil the criteria from above.	First administration until 31-38 days	Yes
Secondary	Blood Transfusion	Blood transfusion for treated and operated patients on Day of surgery.	Day 1	No
Secondary	Volume of Blood Loss	Volume of blood loss for treated and operated patients during surgery.	Day 1	No
Secondary	Laboratory Analyses	Frequency of patients with possible clinically significant abnormalities.	First administration to end of study	No

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