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

NCT01184989 | Completed Phase 4 Results

• 2 other identifiers: 1160.862010-018723-26
• Study Type: interventional
• Target: 142
• Locations: 6 countries
• Sites: 10

Brief 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.

Conditions

Arthroplasty, Replacement; Prevention of Venous Thromboembolism; Moderate Renal Impairment (CrCl 30-50 mL/Min)

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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

  At day 6 before drug intake (di), at 1h, 2h, 4h, 8h and 24h after di

Study Arms (1)

Dabigatran etexilate

OTHER

open label, once daily dose approved by EMEA and Health Canada

Drug: Dabigatran etexilate

Interventions

Dabigatran etexilate DRUG

once daily approved dose by EMEA and Health Canada

Dabigatran etexilate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (10)

1160.86.43001 Boehringer Ingelheim Investigational Site

Graz, Austria

Location

1160.86.43003 Boehringer Ingelheim Investigational Site

Vienna, Austria

Location

1160.86.01001 Boehringer Ingelheim Investigational Site

Red Deer, Alberta, Canada

Location

1160.86.01002 Boehringer Ingelheim Investigational Site

Halifax, Nova Scotia, Canada

Location

1160.86.01003 Boehringer Ingelheim Investigational Site

Charlottetown, Prince Edward Island, Canada

Location

1160.86.42002 Boehringer Ingelheim Investigational Site

Prague, Czechia

Location

1160.86.35801 Boehringer Ingelheim Investigational Site

Jyväskylä, Finland

Location

1160.86.31002 Boehringer Ingelheim Investigational Site

Hilversum, Netherlands

Location

1160.86.46002 Boehringer Ingelheim Investigational Site

Hässleholm, Sweden

Location

1160.86.46001 Boehringer Ingelheim Investigational Site

Mölndal, Sweden

Location

MeSH Terms

Interventions

Dabigatran

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2010
• First Posted: August 19, 2010
• Study Start: August 1, 2010
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: September 25, 2018
• Results First Posted: May 23, 2014

Record last verified: 2018-08

Locations

AU (2); FI (1); CA (3); NL (1); CZ (1); SE (2)