Arthroplasty, ReplacementPhase 4NCT01184989

Treatment of Patients Undergoing Primary Unilateral Elective Total Knee or Hip Replacement With Dabigatran Etexilate

A Phase 4 study testing Dabigatran etexilate in people with Arthroplasty, Replacement and Prevention of Venous Thromboembolism, run by Boehringer Ingelheim at 10 sites in 6 countries.

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

To supplement the current evidence of the effect of Pradaxa® (dabigatran etexilate) on coagulation parameters, including a calibrated thrombin time test, in patients with moderate renal impairment undergoing elective total hip- or knee-replacement surgery, this PK/PD study will be conducted. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Arthroplasty, Replacement, Prevention of Venous Thromboembolism, Moderate Renal Impairment (CrCl 30-50 mL/Min)
What is being tested?: Dabigatran etexilate
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 142 participants
Where: 10 sitesin 6 countries
Study dates: Aug 2010to Apr 2013
Phase: Phase 4
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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients scheduled for primary unilateral elective total knee or hip replacement, male or female being 18 years or older
Moderate renal impairment (CrCl 30-50 mL/min)
Written informed consent
Caucasian patients

Who cannot join

Patients weighing less than 40 kg.
Patients requiring chronic treatment with anticoagulants (e.g. vitamin K antagonists; e.g. patients with atrial fibrillation, patients with artificial heart valves, etc.).
Patients who in the investigator's judgment were perceived as having an excessive risk of bleeding, for example:
Constitutional or acquired coagulation disorders
History of bleeding diathesis
Clinically relevant bleeding (gastrointestinal, pulmonary, intraocular or urogenital bleeding) within 3 months of enrolment

Show all 27Show fewer

Major surgery or trauma (e.g. hip fracture) within 3 months of enrolment
History of thrombocytopenia, including heparin-induced thrombocytopenia, or a platelet count <100 000 cells/microliter at randomization
Any history of hemorrhagic stroke or any of the following intracranial pathologies: bleeding, neoplasm
Any arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities
Presence of malignant neoplasms at higher risk of bleeding
Known or suspected oesophageal varices
Symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30 days
Treatment with anticoagulants, clopidogrel, ticlopidine, abciximab, aspirin >162.5 mg/day or non-steroidal anti-inflammatory drug (NSAID) with t1/2>12 hours within 7 days prior to hip or knee replacement surgery OR anticipated need while the patient was receiving study medication and prior to 24 hours after the last administration of study medication (COX-2 selective inhibitors are allowed) because of anticipated need of quinidine, verapamil or other restricted medication during the treatment period
Recent unstable cardiovascular disease (in the investigator's opinion) such as uncontrolled hypertension, that was ongoing at the time of enrolment or history of myocardial infarction within 3 months of enrolment.
Ongoing treatment for VTE.
Liver disease expected to have any potential impact on survival (i.e. hepatitis B or C, cirrhosis) or ALT/AST >3x upper limit of normal range (ULN). This did not include Gilbert's syndrome or hepatitis A with complete recovery.
Known severe renal insufficiency (CrCl <30 mL/min) and patients with mild renal insufficiency (CrCl >50 mL/min) or normal renal function.
Planned anaesthesia with post-operative indwelling epidural catheters.
Pre-menopausal women (last menstruation <=1 year prior to signing informed consent), who were:
Pregnant
Nursing
Of child-bearing potential and were NOT practicing acceptable methods of birth control, or did NOT plan to continue practicing an acceptable method throughout the study. Acceptable methods of birth control included intrauterine device; oral, implantable or injectable contraceptives and surgical sterility
Hypersensitivity to dabigatran etexilate or to any of excipients.
Participation in a clinical trial within 30 days of enrolment.
Known alcohol or drug abuse which would interfere with completion of the study; patients considered unreliable by the investigator concerning the requirements for follow-up during the study and/or compliance with study drug administration.
Previous participation in this study.

Trial locations and contacts

10 sites in 6 countries.

Country

City, postcode or hospital

10 sites in 6 countries

Canada3 sites

1160.86.01003 Boehringer Ingelheim Investigational Site
Charlottetown, Prince Edward Island
1160.86.01002 Boehringer Ingelheim Investigational Site
Halifax, Nova Scotia
1160.86.01001 Boehringer Ingelheim Investigational Site
Red Deer, Alberta

Other trials in Canada

Austria2 sites

1160.86.43001 Boehringer Ingelheim Investigational Site
Graz
1160.86.43003 Boehringer Ingelheim Investigational Site
Vienna

Other trials in Austria

Sweden2 sites

1160.86.46002 Boehringer Ingelheim Investigational Site
Hässleholm
1160.86.46001 Boehringer Ingelheim Investigational Site
Mölndal

Other trials in Sweden

Czechia1 site

1160.86.42002 Boehringer Ingelheim Investigational Site
Prague

Other trials in Czechia

Finland1 site

1160.86.35801 Boehringer Ingelheim Investigational Site
Jyväskylä

Other trials in Finland

Netherlands1 site

1160.86.31002 Boehringer Ingelheim Investigational Site
Hilversum

Other trials in Netherlands

About this study

Official title: An Open Label, Non-comparative, Pharmacokinetic and Pharmacodynamic Study to Evaluate the Effect of Dabigatran Etexilate on Coagulation Parameters Including a Calibrated Thrombin Time Test in Patients With Moderate Renal Impairment (Creatinine Clearance 30-50 ml/Min) Undergoing Primary Unilateral Elective Total Knee or Hip Replacement Surgery

Conditions: Arthroplasty, Replacement, Prevention of Venous Thromboembolism, Moderate Renal Impairment (CrCl 30-50 mL/Min)
Being tested: Dabigatran etexilate

What participants receive

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

Dabigatran etexilateDrug
once daily approved dose by EMEA and Health Canada

Study groups in NCT01184989
Study group	Role	What they receive
Dabigatran etexilate	Other	open label, once daily dose approved by EMEA and Health Canada Receives: Drug: Dabigatran etexilate

What is being measured

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

Dabigatran Concentration in Plasma, Estimated From Local Hemoclot®
The Hemoclot® test kit measures the dTT (diluted Thrombin time). In the present trial, as a first step, the dTT in calibration samples that had known Dabigatran concentrations was measured locally with the Hemoclot® test kit, and a linear calibration curve was fitted to the data from the calibration samples. Thereafter, for each patient at each time-point, the dTT was measured with the Hemoclot® kit and the Dabigatran concentration was read off from the calibration curve.
These estimated concentrations are compared with concentrations measured in parallel with HPLC-MS/MS.
As the trial objective is the method comparison and not the detection of the absolute concentrations of either of the methods, the result is reported as a relative bioavailability [%], see "Statistical Analysis 1" below. Only concentrations >= LLOQ (Lower Limit of concentration) are included in the quantitative comparison.
Measured: Screening, day of surgery 1 hour (h) and 2h after drug intake (di) for late finalization of surgery, 4h and 8h after di for early finalization of surgery, 15 minutes (min) before di at days 2, 3, 4, 5 and 6, at day 6 also 1h, 2h, 4h, 8h and 24 after di
Dabigatran Concentration in Plasma, Estimated From Central Hemoclot®
The Hemoclot® test kit measures the dTT (diluted Thrombin time). In the present trial, as a first step, the dTT in calibration samples that had known Dabigatran concentrations was measured centrally with the Hemoclot® test kit, and a linear calibration curve was fitted to the data from the calibration samples. Thereafter, for each patient at each time-point, the dTT was measured with the Hemoclot® kit and the Dabigatran concentration was read off from the calibration curve.
These estimated concentrations are compared with concentrations measured in parallel with HPLC-MS/MS.
As the trial objective is the method comparison and not the detection of the absolute concentrations of either of the methods, the result is reported as a relative bioavailability [%], see "Statistical Analysis 1" below. Only concentrations >= LLOQ (Lower Limit of concentration) are included in the quantitative comparison.
Measured: Screening, day of surgery 1 hour (h) and 2h after drug intake (di) for late finalization of surgery, 4h and 8h after di for early finalization of surgery, 15 minutes (min) before di at days 2, 3, 4, 5 and 6, at day 6 also 1h, 2h, 4h, 8h and 24 after di
Dabigatran Concentration in Plasma, Measured With HPLC-MS/MS
Dabigatran Concentration in Plasma, measured with HPLC-MS/MS - Most relevant timepoints are reported here, ie timepoints of day 6
Measured: At day 6 before drug intake (di), at 1h, 2h, 4h, 8h and 24h after di

Timeline

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

Aug 2010Apr 2013

First posted19 Aug 2010 (estimated)
Study startAug 2010
Primary completionApr 2013
Study completionApr 2013

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, ReplacementStudies 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 4
Primary purpose: Prevention
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 142 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01184989
Sponsor's protocol ID: 1160.86
Other IDs: 2010-018723-26
Status last verified: Aug 2018
First submitted: 16 Aug 2010
Last updated: 25 Sep 2018
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

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Comparison of Functional Results of ADM X3-MoP Cup (Stryker) and a CoC Cup (Zimmer) in Young Patients
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Active, not recruiting
At Home, Digital Rehabilitation for Patients After Reverse Total Shoulder Arthroplasty
Arthroplasty, Replacement, Shoulder, Reverse Total Shoulder Arthroplasty
Enrolling by invitationObservational study
Persona SoluTion PPS Femur PMCF
Rhematoid Arthritis, Osteo Arthritis of the Knee
Not yet recruiting
Negative Pressure Wound Therapy Devices in Total Knee Arthroplasty
Wound Surgical, Diabetes
Active, not recruiting
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Arthroplasty, Overweight and Obesity

All Arthroplasty, Replacement trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open Label, Non-comparative, Pharmacokinetic and Pharmacodynamic Study to Evaluate the Effect of Dabigatran Etexilate on Coagulation Parameters Including a Calibrated Thrombin Time Test in Patients With Moderate Renal Impairment (Creatinine Clearance 30-50 ml/Min) Undergoing Primary Unilateral Elective Total Knee or Hip Replacement Surgery
ClinicalTrials.gov ID: NCT01184989
Acronym / sponsor ID: 1160.86
Conditions: Arthroplasty, Replacement, Prevention of Venous Thromboembolism, Moderate Renal Impairment (CrCl 30-50 mL/Min)
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 142 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Aug 2010
Primary completion: Apr 2013 (actual)
Study completion: Apr 2013 (actual)
First posted: 19 Aug 2010 (estimated)
Results: Posted 23 May 2014

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: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Dabigatran etexilate	Other	Drug: Dabigatran etexilateopen label, once daily dose approved by EMEA and Health Canada

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Patients scheduled for primary unilateral elective total knee or hip replacement, male or female being 18 years or older
Moderate renal impairment (CrCl 30-50 mL/min)
Written informed consent
Caucasian patients

Key exclusion criteria (27 listed)

Patients weighing less than 40 kg.
Patients requiring chronic treatment with anticoagulants (e.g. vitamin K antagonists; e.g. patients with atrial fibrillation, patients with artificial heart valves, etc.).
Patients who in the investigator's judgment were perceived as having an excessive risk of bleeding, for example:
Constitutional or acquired coagulation disorders
History of bleeding diathesis

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 etexilateonce daily approved dose by EMEA and Health Canada	Drug	Dabigatran etexilate

Primary outcome

Dabigatran Concentration in Plasma, Estimated From Local Hemoclot®
Time frame: Screening, day of surgery 1 hour (h) and 2h after drug intake (di) for late finalization of surgery, 4h and 8h after di for early finalization of surgery, 15 minutes (min) before di at days 2, 3, 4, 5 and 6, at day 6 also 1h, 2h, 4h, 8h and 24 after di
The Hemoclot® test kit measures the dTT (diluted Thrombin time). In the present trial, as a first step, the dTT in calibration samples that had known Dabigatran concentrations was measured locally with the Hemoclot® test kit, and a linear calibration curve was fitted to the data from the calibration samples. Thereafter, for each patient at each time-point, the dTT was measured with the Hemoclot® kit and the Dabigatran concentration was read off from the calibration curve. These estimated concentrations are compared with concentrations measured in parallel with HPLC-MS/MS. As the trial objective is the method comparison and not the detection of the absolute concentrations of either of the methods, the result is reported as a relative bioavailability [%], see "Statistical Analysis 1" below. Only concentrations >= LLOQ (Lower Limit of concentration) are included in the quantitative comparison.
Dabigatran Concentration in Plasma, Estimated From Central Hemoclot®
Time frame: Screening, day of surgery 1 hour (h) and 2h after drug intake (di) for late finalization of surgery, 4h and 8h after di for early finalization of surgery, 15 minutes (min) before di at days 2, 3, 4, 5 and 6, at day 6 also 1h, 2h, 4h, 8h and 24 after di
The Hemoclot® test kit measures the dTT (diluted Thrombin time). In the present trial, as a first step, the dTT in calibration samples that had known Dabigatran concentrations was measured centrally with the Hemoclot® test kit, and a linear calibration curve was fitted to the data from the calibration samples. Thereafter, for each patient at each time-point, the dTT was measured with the Hemoclot® kit and the Dabigatran concentration was read off from the calibration curve. These estimated concentrations are compared with concentrations measured in parallel with HPLC-MS/MS. As the trial objective is the method comparison and not the detection of the absolute concentrations of either of the methods, the result is reported as a relative bioavailability [%], see "Statistical Analysis 1" below. Only concentrations >= LLOQ (Lower Limit of concentration) are included in the quantitative comparison.
Dabigatran Concentration in Plasma, Measured With HPLC-MS/MS
Time frame: At day 6 before drug intake (di), at 1h, 2h, 4h, 8h and 24h after di
Dabigatran Concentration in Plasma, measured with HPLC-MS/MS - Most relevant timepoints are reported here, ie timepoints of day 6

Results and safety

Results posted to the registry on 23 May 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Patients Treated With Dabigatran Etexilate	112	100

Primary outcome: Dabigatran Concentration in Plasma, Estimated From Local Hemoclot®

Time frame: Screening, day of surgery 1 hour (h) and 2h after drug intake (di) for late finalization of surgery, 4h and 8h after di for early finalization of surgery, 15 minutes (min) before di at days 2, 3, 4, 5 and 6, at day 6 also 1h, 2h, 4h, 8h and 24 after di. Number. Unit: measurements estimated as above LLOQ

Measure	Patients Treated With Dabigatran Etexilate n = 99
Value	136 (NA)

Patients Treated With Dabigatran Etexilate: Ratio: 102.16 (90% CI 97.640 to 106.893), Geometric Mean

Population analysed: Correct calculation set: all patients of the Per Protocol set (PPS) (patients with at least one pair of observations for both PD and PK parameters without important protocol violations) and additionally all patients of the TS whom the only reason for not being in the PPS was the non-influential forbidden concomitant medication or vomiting

Primary outcome: Dabigatran Concentration in Plasma, Estimated From Central Hemoclot®

Measure	Patients Treated With Dabigatran Etexilate n = 97
Value	468

Patients Treated With Dabigatran Etexilate: Ratio: 92.37 (90% CI 90.079 to 94.719), Geometric Mean

Primary outcome: Dabigatran Concentration in Plasma, Measured With HPLC-MS/MS

Time frame: At day 6 before drug intake (di), at 1h, 2h, 4h, 8h and 24h after di. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Patients Treated With Dabigatran Etexilate n = 96
before intake(N=96)	47.5 (84.7)
after 1h(N=93)	87.8 (81.9)
after 2h(N=91)	147 (85.2)
after 4h(N=88)	157 (84.8)
after 8h(N=93)	119 (78.1)
after 24h(N=86)	47.7 (90.5)

Adverse events

Time frame: Up to 14 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Patients Treated With Dabigatran Etexilate	10 of 112 (8.9%)	99 of 112 (88.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.

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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

10 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dabigatran etexilate in people with Arthroplasty, Replacement and Prevention of Venous Thromboembolism, run by Boehringer Ingelheim at 10 sites in 6 countries.

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 27 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 25 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Canada, Austria, Sweden, Czechia, Finland and 1 more country. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 23 May 2014). 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?

Dabigatran Concentration in Plasma, Estimated From Local Hemoclot® (time frame: Screening, day of surgery 1 hour (h) and 2h after drug intake (di) for late finalization of surgery, 4h and 8h after di for early finalization of surgery, 15 minutes (min) before di at days 2, 3, 4, 5 and 6, at day 6 also 1h, 2h, 4h, 8h and 24 after di). The study lists 3 primary outcomes in all. 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 NCT01184989.

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 25 Sep 2018.