A Phase 4 interventional study of Dabigatran etexilate in Arthroplasty, Replacement, Prevention of Venous Thromboembolism and Moderate Renal Impairment (CrCl 30-50 mL/Min), sponsored by Boehringer Ingelheim. Completed at 10 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-09-25.
Sponsored by Boehringer Ingelheim · Phase 4, Interventional, and Prevention
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.
1,995 studies on the registry are indexed under Renal Insufficiency; 173 are open to participants now.
This study's enrollment of 142 is above the median of 43 across 1,504 interventional studies indexed under Renal Insufficiency.
Browse Renal Insufficiency studies →Boehringer Ingelheim is the lead sponsor of 2,245 studies on the registry; 58 are open to participants now.
Of its 162 completed or terminated interventional studies of FDA-regulated products, 116 (72%) have results posted.
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Exclusion criteria:
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
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
open label, once daily dose approved by EMEA and Health Canada
Drug: Dabigatran etexilate
once daily approved dose by EMEA and Health Canada
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.
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
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.
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
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
Time frame: At day 6 before drug intake (di), at 1h, 2h, 4h, 8h and 24h after di
| Milestone | Patients Treated With Dabigatran Etexilate |
|---|---|
| Started | 112 |
| Completed | 100 |
| Not completed | 12 |
| Withdrew: Adverse event | 11 |
| Withdrew: Withdrawal by subject | 1 |
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.
| measurements estimated as above LLOQ | Patients Treated With Dabigatran Etexilate |
|---|---|
| Dabigatran Concentration in Plasma, Estimated From Local Hemoclot® | 136 ± NA |
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.
| measurements estimated as above LLOQ | Patients Treated With Dabigatran Etexilate |
|---|---|
| Dabigatran Concentration in Plasma, Estimated From Central Hemoclot® | 468 |
Dabigatran Concentration in Plasma, measured with HPLC-MS/MS - Most relevant timepoints are reported here, ie timepoints of day 6
| ng/mL | Patients Treated With Dabigatran Etexilate |
|---|---|
| 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 |
Collected over Up to 14 days. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Patients Treated With Dabigatran Etexilate | — | 10/112 (8.9%) | 99/112 (88.4%) |
| Event | Patients Treated With Dabigatran Etexilate |
|---|---|
| Gastric ulcerGastrointestinal disorders | 2/112 |
| HaematemesisGastrointestinal disorders | 2/112 |
| Gastritis haemorrhagicGastrointestinal disorders | 1/112 |
| DiverticulitisInfections and infestations | 1/112 |
| PyelonephritisInfections and infestations | 1/112 |
| Urinary tract infectionInfections and infestations | 1/112 |
| UrosepsisInfections and infestations | 1/112 |
| Atrial fibrillationCardiac disorders | 1/112 |
| Acute myocardial infarctionCardiac disorders | 1/112 |
| Wound secretionInjury, poisoning and procedural complications | 1/112 |
| Event | Patients Treated With Dabigatran Etexilate |
|---|---|
| NauseaGastrointestinal disorders | 45/112 |
| VomitingGastrointestinal disorders | 37/112 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 23/112 |
| DizzinessNervous system disorders | 14/112 |
| HypotensionVascular disorders | 11/112 |
| ConstipationGastrointestinal disorders | 11/112 |
| Haemoglobin decreasedInvestigations | 11/112 |
| Oedema peripheralGeneral disorders | 9/112 |
| AnaemiaBlood and lymphatic system disorders | 7/112 |
| Urinary retentionRenal and urinary disorders | 7/112 |
Treated Set (TS): Patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
| Age, Continuous(years) | Patients Treated With Dabigatran Etexilate |
|---|---|
| Mean | 79.1 ± 6.5 |
| Sex: Female, Male(Participants) | Patients Treated With Dabigatran Etexilate |
|---|---|
| Female | 78 |
| Male | 34 |
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Boehringer Ingelheim