Arthroplasty, Replacement, KneePhase 2NCT00246025

A Study of BIBR 1048 in Prevention of Venous Thromboembolism in Patients With TKR Surgery.

A Phase 2 study testing Dabigatran etexilate in people with Arthroplasty, Replacement, Knee and Venous Thrombosis, run by Boehringer Ingelheim at 38 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The goal of this study is to evaluate the comparative efficacy and safety of three different doses ( 110 mg, 150 mg, 220 mg) of BIBR 1048 (Dabigatran etexilate) orally, compared to placebo, in prevention of venous thromboembolism in patient with primary elective total knee replacement surgery, and to evaluate… Read more about this study

Who is it for?: Ages 20 years and older
Conditions the study is for: Arthroplasty, Replacement, Knee, Venous Thrombosis
What is being tested?: Dabigatran etexilate
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 512 participants
Where: 38 sitesJapan
Study dates: Oct 2005to Jun 2007
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients scheduled to undergo a primary, unilateral elective total knee replacement
Male or Female 20 years of age or order
Patients weighing at least 40 kg
Written informed consent prior to the start of study participation

Who cannot join

History of bleeding diathesis
Constitutional or acquired coagulation disorders that in the investigator's judgment puts the patient at excessive risk for bleeding
Major surgery or trauma (e.g. hip fracture) within the last 3 months
Recent unstable cardiovascular disease, such as uncontrolled hypertension at the time of enrollment (investigator's judgment) or history of myocardial infarction within the last 3 months
Any history of hemorrhagic stroke or any of the following intracranial pathologies: bleeding, neoplasm, AV (arteriovenous) malformation or aneurysm or recent bleeding history
Condition requiring anti-coagulant therapy
Elevated AST(Aspartate Aminotransferase) , ALT(Alanine Aminotransferase), or any history of clinically relevant liver disease
Patients with a history of clinically significant renal diseases or with elevated creatinine values

Trial locations and contacts

38 sites in 1 country.

City, postcode or hospital

38 sites in 1 country

Japan38 sites

1160.50.001 Boehringer Ingelheim Investigational Site
Eniwa, Hokkaido
1160.50.018 Boehringer Ingelheim Investigational Site
Fukuoka, Fukuoka
1160.50.008 Boehringer Ingelheim Investigational Site
Hachioji, Tokyo
1160.50.006 Boehringer Ingelheim Investigational Site
Hirosaki, Aomori
1160.50.026 Boehringer Ingelheim Investigational Site
Hiroshima, Hiroshima
1160.50.011 Boehringer Ingelheim Investigational Site
Iida, Nagano
1160.50.024 Boehringer Ingelheim Investigational Site
Izumisano, Osaka
1160.50.045 Boehringer Ingelheim Investigational Site
Izunokuni,Shizuoka
1160.50.022 Boehringer Ingelheim Investigational Site
Kagoshima, Kagoshima
1160.50.027 Boehringer Ingelheim Investigational Site
Kawasaki, Kanagawa
1160.50.032 Boehringer Ingelheim Investigational Site
Kawasaki, Kanagawa
1160.50.041 Boehringer Ingelheim Investigational Site
Kitakyusyu, Fukuoka
1160.50.039 Boehringer Ingelheim Investigational Site
Koshigaya,Saitama
1160.50.037 Boehringer Ingelheim Investigational Site
Kurume ,Fukuoka
1160.50.038 Boehringer Ingelheim Investigational Site
Kurume ,Fukuoka
1160.50.013 Boehringer Ingelheim Investigational Site
Kyoto, Kyoto
1160.50.036 Boehringer Ingelheim Investigational Site
Matsue, Shimane
1160.50.042 Boehringer Ingelheim Investigational Site
Miyazaki, Miyazaki
1160.50.028 Boehringer Ingelheim Investigational Site
Musashimurayama, Tokyo
1160.50.005 Boehringer Ingelheim Investigational Site
Obihiro, Hokkaido
1160.50.030 Boehringer Ingelheim Investigational Site
Okayama, Okayama
1160.50.021 Boehringer Ingelheim Investigational Site
Omura, Nagasaki
1160.50.014 Boehringer Ingelheim Investigational Site
Osaka, Osaka
1160.50.015 Boehringer Ingelheim Investigational Site
Osaka, Osaka
1160.50.016 Boehringer Ingelheim Investigational Site
Osaka, Osaka
1160.50.033 Boehringer Ingelheim Investigational Site
Osaka, Osaka
1160.50.031 Boehringer Ingelheim Investigational Site
Saga, Saga
1160.50.009 Boehringer Ingelheim Investigational Site
Sagamihara, Kanagawa
1160.50.002 Boehringer Ingelheim Investigational Site
Sapporo, Hokkaido
1160.50.004 Boehringer Ingelheim Investigational Site
Sapporo, Hokkaido
1160.50.020 Boehringer Ingelheim Investigational Site
Sasebo, Nagasaki
1160.50.025 Boehringer Ingelheim Investigational Site
Sasebo, Nagasaki
1160.50.034 Boehringer Ingelheim Investigational Site
Sendai, Miyagi
1160.50.029 Boehringer Ingelheim Investigational Site
Shinjuku-ku,Tokyo
1160.50.043 Boehringer Ingelheim Investigational Site
Shizuoka, Shizuoka
1160.50.044 Boehringer Ingelheim Investigational Site
Sumida-ku, Tokyo
1160.50.023 Boehringer Ingelheim Investigational Site
Tomigusuku, Okinawa
1160.50.040 Boehringer Ingelheim Investigational Site
Tsukuba , Ibaraki

Other trials in Japan

About this study

Official title: A Randomised, Parallel-group, Double-blind, Placebo Controlled Study to Investigate the Efficacy and Safety of BIBR 1048 in Prevention of Venous Thromboembolism in Patients With Primary Elective Total Knee Replacement Surgery

Conditions: Arthroplasty, Replacement, Knee, Venous Thrombosis
Being tested: Dabigatran etexilate, placebo
Medical subject headings: Venous Thrombosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Dabigatran etexilateDrug
Dabigatran etexilate 110 mg capsule, once a day, oral administration
Dabigatran etexilateDrug
Dabigatran etexilate 150 mg capsule, once a day, oral administration
Dabigatran EtexilateDrug
Dabigatran etexilate 220 mg capsule, once a day, oral administration
placeboDrug
matching placebo capsule, once a day, oral administration

Study groups in NCT00246025
Study group	Role	What they receive
Dabigatran etexilate 110 mg	Experimental	Dabigatran etexilate 110 mg capsule, once a day, oral administration Receives: Drug: Dabigatran etexilate
Dabigatran etexilate 150 mg	Experimental	Dabigatran etexilate 150 mg capsule, once a day, oral administration Receives: Drug: Dabigatran etexilate
Dabigatran etexilate 220 mg	Experimental	Dabigatran etexilate 110 mg capsule, 2capsules, once a day, oral administration Receives: Drug: Dabigatran Etexilate
Placebo	Placebo comparator	matching placebo capsule, once a day, oral administration Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Participants Who Have a Composite Endpoint Consisting of Total Venous Thromboembolic Event (VTE) and All Cause Mortality During the Treatment Period.
number of participants with the composite endpoint (total Venous Thromboembolic Event (VTE) and all cause mortality
Measured: 2 weeks study medication

Secondary outcomes (10)

Percentage of Participants Who Have a Composite of Major VTE (Defined as Proximal DVT and PE) and VTE Related Mortality
Number of participants with the composite of major VTE (defined as proximal DVT and PE) and VTE related mortality
Measured: 2 weeks
Percentage of Participants Who Have Proximal DVT (Deep Vein Thrombosis) During Treatment Period
Number of participants who have Proximal DVT during treatment period
Measured: 2 weeks
Percentage of Participants With Symptomatic DVT (Deep Vein Thrombosis)
Number of Participants expressing DVT with symptoms
Measured: 2 weeks
Percentage of Participants Who Have Total DVT (Deep Vein Thrombosis) During Treatment Period
Number of participants who have Total DVT during treatment period
Measured: 2 weeks
Number of Participants With Pulmonary Embolism During Treatment Period
Pulmonary embolism confirmed by pulmonary scintigraphy, pulmonary angiography or contrast CT.
Measured: 2 weeks
Number of Participants Who Died During Treatment Period
All cause death, as adjudicated by the VTE events committee.
Measured: 2 weeks
Number of Participants With Bleeding Events During Treatment Period
Major bleeding events were defined as
- fatal
- clinically overt associated with loss of haemoglobin >=2g/dL 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 (more than a spot on toilet paper)
- 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.
Measured: 2 weeks
Blood Transfusion
Blood transfusion for treated and operated patients on Day of surgery.
Measured: Day 0
Volume of Blood Loss
Volume of blood loss for treated and operated patients during surgery.
Measured: Day 0
Laboratory Analyses
Frequency of patients with possible clinically significant abnormalities.
Measured: First administration to end of study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2005Jun 2007

First posted31 Oct 2005 (estimated)
Study startOct 2005
Primary completionJun 2007

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Arthroplasty, Replacement, KneeStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Enrolment: 512 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00246025
Sponsor's protocol ID: 1160.50
Status last verified: Feb 2014
First submitted: 28 Oct 2005
Last updated: 9 Jun 2014
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 3
REGN7508 Versus Apixaban and Enoxaparin for Thromboprophylaxis After Total Knee Arthroplasty in Adults
Venous Thromboembolism (VTE)
Recruiting
SII Levels Following iPACK Block With Adductor Canal Block in Knee Arthroplasty
Knee Osteoarthritis
Enrolling by invitationObservational study
Persona SoluTion PPS Femur PMCF
Rhematoid Arthritis, Osteo Arthritis of the Knee
Recruiting
ACB and iPACK Blocks With Intravenous Dexamethasone and Perineural Dexmedetomidine in Total Knee Arthroplasty
Knee Osteoarthritis
RecruitingPhase 3
REGN7508 Versus Acetylsalicylic Acid (ASA) for Venous Thromboprophylaxis After Total Knee Arthroplasty in Adult Participants
Symptomatic Venous Thromboembolism (VTE)

All Arthroplasty, Replacement, Knee trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomised, Parallel-group, Double-blind, Placebo Controlled Study to Investigate the Efficacy and Safety of BIBR 1048 in Prevention of Venous Thromboembolism in Patients With Primary Elective Total Knee Replacement Surgery
ClinicalTrials.gov ID: NCT00246025
Acronym / sponsor ID: 1160.50
Conditions: Arthroplasty, Replacement, Knee, Venous Thrombosis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 512 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Oct 2005
Primary completion: Jun 2007 (actual)
First posted: 31 Oct 2005 (estimated)
Results: Posted 17 Dec 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Number of arms: 4

Arm	Type	Receives
Dabigatran etexilate 110 mg	Experimental	Drug: Dabigatran etexilateDabigatran etexilate 110 mg capsule, once a day, oral administration
Dabigatran etexilate 150 mg	Experimental	Drug: Dabigatran etexilateDabigatran etexilate 150 mg capsule, once a day, oral administration
Dabigatran etexilate 220 mg	Experimental	Drug: Dabigatran EtexilateDabigatran etexilate 110 mg capsule, 2capsules, once a day, oral administration
Placebo	Placebo comparator	Drug: placebomatching placebo capsule, once a day, oral administration

Who may qualify

Ages: 20 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Patients scheduled to undergo a primary, unilateral elective total knee replacement
Male or Female 20 years of age or order
Patients weighing at least 40 kg
Written informed consent prior to the start of study participation

Key exclusion criteria (8 listed)

History of bleeding diathesis
Constitutional or acquired coagulation disorders that in the investigator's judgment puts the patient at excessive risk for bleeding
Major surgery or trauma (e.g. hip fracture) within the last 3 months
Recent unstable cardiovascular disease, such as uncontrolled hypertension at the time of enrollment (investigator's judgment) or history of myocardial infarction within the last 3 months
Any history of hemorrhagic stroke or any of the following intracranial pathologies: bleeding, neoplasm, AV (arteriovenous) malformation or aneurysm or recent bleeding history

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Dabigatran etexilateDabigatran etexilate 110 mg capsule, once a day, oral administration	Drug	Dabigatran etexilate 110 mg
Dabigatran etexilateDabigatran etexilate 150 mg capsule, once a day, oral administration	Drug	Dabigatran etexilate 150 mg
Dabigatran EtexilateDabigatran etexilate 220 mg capsule, once a day, oral administration	Drug	Dabigatran etexilate 220 mg
placebomatching placebo capsule, once a day, oral administration	Drug	Placebo

Primary outcome

Percentage of Participants Who Have a Composite Endpoint Consisting of Total Venous Thromboembolic Event (VTE) and All Cause Mortality During the Treatment Period.
Time frame: 2 weeks study medication
number of participants with the composite endpoint (total Venous Thromboembolic Event (VTE) and all cause mortality

10 secondary outcomes

Percentage of Participants Who Have a Composite of Major VTE (Defined as Proximal DVT and PE) and VTE Related Mortality
Time frame: 2 weeks
Percentage of Participants Who Have Proximal DVT (Deep Vein Thrombosis) During Treatment Period
Time frame: 2 weeks
Percentage of Participants With Symptomatic DVT (Deep Vein Thrombosis)
Time frame: 2 weeks
Percentage of Participants Who Have Total DVT (Deep Vein Thrombosis) During Treatment Period
Time frame: 2 weeks
Number of Participants With Pulmonary Embolism During Treatment Period
Time frame: 2 weeks
Number of Participants Who Died During Treatment Period
Time frame: 2 weeks
Number of Participants With Bleeding Events During Treatment Period
Time frame: 2 weeks
Blood Transfusion
Time frame: Day 0
Volume of Blood Loss
Time frame: Day 0
Laboratory Analyses
Time frame: First administration to end of study

Results and safety

Results posted to the registry on 17 Dec 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment Group With Placebo	124	114
Dabigatran Etexilate 110 mg	133	124
Dabigatran Etexilate 150 mg	126	116
Dabigatran Etexilate 220 mg	129	116

Primary outcome: Percentage of Participants Who Have a Composite Endpoint Consisting of Total Venous Thromboembolic Event (VTE) and All Cause Mortality During the Treatment Period.

Time frame: 2 weeks study medication. Number. Unit: percentage of participants

Measure	Treatment Group With Placebo n = 101	Dabigatran Etexilate 110 mg n = 106	Dabigatran Etexilate 150 mg n = 104	Dabigatran Etexilate 220 mg n = 96
Value	56.4	39.6	32.7	24

Treatment Group With Placebo vs Dabigatran Etexilate 110 mg: Risk Difference (RD): -16.8 (95% CI -30.2 to -3.4), p = 0.0155, normal approximation method
Treatment Group With Placebo vs Dabigatran Etexilate 150 mg: Risk Difference (RD): -23.7 (95% CI -37.0 to -10.5), p = 0.0006, normal approximation method
Treatment Group With Placebo vs Dabigatran Etexilate 220 mg: Risk Difference (RD): -32.5 (95% CI -45.4 to -19.6), p <0.0001, normal approximation method

Population analysed: Full analysis set (FAS) - Full analysis set includes all patients who were randomly assigned to the treatment, received at least one oral dose, went through surgery, had an evaluable venogram for distal and proximal DVT, or had confirmed symptomatic DVT or PE, or died.

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: First administration to end of study. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment Group With Placebo	2 of 124 (1.6%)	62 of 124 (50%)	Not reported
Dabigatran Etexilate 110 mg	3 of 133 (2.3%)	47 of 133 (35.3%)	Not reported
Dabigatran Etexilate 150 mg	3 of 126 (2.4%)	60 of 126 (47.6%)	Not reported
Dabigatran Etexilate 220 mg	2 of 129 (1.6%)	55 of 129 (42.6%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.

Related trials for Arthroplasty, Replacement, Knee

RecruitingPhase 3
REGN7508 Versus Apixaban and Enoxaparin for Thromboprophylaxis After Total Knee Arthroplasty in Adults
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Recruiting
SII Levels Following iPACK Block With Adductor Canal Block in Knee Arthroplasty
Knee Osteoarthritis
Enrolling by invitationObservational study
Persona SoluTion PPS Femur PMCF
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RecruitingPhase 3
REGN7508 Versus Acetylsalicylic Acid (ASA) for Venous Thromboprophylaxis After Total Knee Arthroplasty in Adult Participants
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Boehringer Ingelheim study chair

Boehringer Ingelheim

38 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dabigatran etexilate in people with Arthroplasty, Replacement, Knee and Venous Thrombosis, run by Boehringer Ingelheim at 38 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Dec 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Who Have a Composite Endpoint Consisting of Total Venous Thromboembolic Event (VTE) and All Cause Mortality During the Treatment Period. (time frame: 2 weeks study medication). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00246025.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2014.