Trial Outcomes & Findings for Treatment of Patients Undergoing Primary Unilateral Elective Total Knee or Hip Replacement With Dabigatran Etexilate (NCT NCT01184989)
NCT ID: NCT01184989
Last Updated: 2018-09-25
Results Overview
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.
COMPLETED
PHASE4
142 participants
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
2018-09-25
Participant Flow
30 patients did not receive any study medication.
Participant milestones
| Measure |
Patients Treated With Dabigatran Etexilate
Patients treated with Dabigatran Etexilate 150mg once daily. At the day of surgery the treatment will be initiated 1-4 h post surgery with 75mg.
142 patients were enrolled for the study, but only 112 were treated. Therefore, the number of started patients corresponds to the ones that were actually treated.
|
|---|---|
|
Overall Study
STARTED
|
112
|
|
Overall Study
COMPLETED
|
100
|
|
Overall Study
NOT COMPLETED
|
12
|
Reasons for withdrawal
| Measure |
Patients Treated With Dabigatran Etexilate
Patients treated with Dabigatran Etexilate 150mg once daily. At the day of surgery the treatment will be initiated 1-4 h post surgery with 75mg.
142 patients were enrolled for the study, but only 112 were treated. Therefore, the number of started patients corresponds to the ones that were actually treated.
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|---|---|
|
Overall Study
Adverse Event
|
11
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Treatment of Patients Undergoing Primary Unilateral Elective Total Knee or Hip Replacement With Dabigatran Etexilate
Baseline characteristics by cohort
| Measure |
Patients Treated With Dabigatran Etexilate
n=112 Participants
Patients treated with Dabigatran Etexilate 150mg once daily. At the day of surgery the treatment will be initiated 1-4 h post surgery with 75mg.
|
|---|---|
|
Age, Continuous
|
79.1 years
STANDARD_DEVIATION 6.5 • n=93 Participants
|
|
Sex: Female, Male
Female
|
78 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 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 diPopulation: 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
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.
Outcome measures
| Measure |
Patients Treated With Dabigatran Etexilate
n=320 Measurements
Patients treated with Dabigatran Etexilate 150mg once daily. At the day of surgery the treatment will be initiated 1-4 h post surgery with 75mg.
|
|---|---|
|
Dabigatran Concentration in Plasma, Estimated From Local Hemoclot®
|
136 measurements estimated as above LLOQ
NA
|
PRIMARY outcome
Timeframe: 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 diPopulation: 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
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.
Outcome measures
| Measure |
Patients Treated With Dabigatran Etexilate
n=1158 Measurements
Patients treated with Dabigatran Etexilate 150mg once daily. At the day of surgery the treatment will be initiated 1-4 h post surgery with 75mg.
|
|---|---|
|
Dabigatran Concentration in Plasma, Estimated From Central Hemoclot®
|
468 measurements estimated as above LLOQ
|
PRIMARY outcome
Timeframe: At day 6 before drug intake (di), at 1h, 2h, 4h, 8h and 24h after diPopulation: 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
Dabigatran Concentration in Plasma, measured with HPLC-MS/MS - Most relevant timepoints are reported here, ie timepoints of day 6
Outcome measures
| Measure |
Patients Treated With Dabigatran Etexilate
n=96 Participants
Patients treated with Dabigatran Etexilate 150mg once daily. At the day of surgery the treatment will be initiated 1-4 h post surgery with 75mg.
|
|---|---|
|
Dabigatran Concentration in Plasma, Measured With HPLC-MS/MS
before intake(N=96)
|
47.5 ng/mL
Geometric Coefficient of Variation 84.7
|
|
Dabigatran Concentration in Plasma, Measured With HPLC-MS/MS
after 1h(N=93)
|
87.8 ng/mL
Geometric Coefficient of Variation 81.9
|
|
Dabigatran Concentration in Plasma, Measured With HPLC-MS/MS
after 2h(N=91)
|
147 ng/mL
Geometric Coefficient of Variation 85.2
|
|
Dabigatran Concentration in Plasma, Measured With HPLC-MS/MS
after 4h(N=88)
|
157 ng/mL
Geometric Coefficient of Variation 84.8
|
|
Dabigatran Concentration in Plasma, Measured With HPLC-MS/MS
after 8h(N=93)
|
119 ng/mL
Geometric Coefficient of Variation 78.1
|
|
Dabigatran Concentration in Plasma, Measured With HPLC-MS/MS
after 24h(N=86)
|
47.7 ng/mL
Geometric Coefficient of Variation 90.5
|
Adverse Events
Patients Treated With Dabigatran Etexilate
Serious adverse events
| Measure |
Patients Treated With Dabigatran Etexilate
n=112 participants at risk
Patients treated with Dabigatran Etexilate 150mg once daily. At the day of surgery the treatment will be initiated 1-4 h post surgery with 75mg.
|
|---|---|
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Gastrointestinal disorders
Gastric ulcer
|
1.8%
2/112 • Up to 14 days
|
|
Gastrointestinal disorders
Haematemesis
|
1.8%
2/112 • Up to 14 days
|
|
Gastrointestinal disorders
Gastritis haemorrhagic
|
0.89%
1/112 • Up to 14 days
|
|
Infections and infestations
Diverticulitis
|
0.89%
1/112 • Up to 14 days
|
|
Infections and infestations
Pyelonephritis
|
0.89%
1/112 • Up to 14 days
|
|
Infections and infestations
Urinary tract infection
|
0.89%
1/112 • Up to 14 days
|
|
Infections and infestations
Urosepsis
|
0.89%
1/112 • Up to 14 days
|
|
Cardiac disorders
Atrial fibrillation
|
0.89%
1/112 • Up to 14 days
|
|
Cardiac disorders
Acute myocardial infarction
|
0.89%
1/112 • Up to 14 days
|
|
Injury, poisoning and procedural complications
Wound secretion
|
0.89%
1/112 • Up to 14 days
|
|
Surgical and medical procedures
Post procedural drainage
|
0.89%
1/112 • Up to 14 days
|
Other adverse events
| Measure |
Patients Treated With Dabigatran Etexilate
n=112 participants at risk
Patients treated with Dabigatran Etexilate 150mg once daily. At the day of surgery the treatment will be initiated 1-4 h post surgery with 75mg.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
6.2%
7/112 • Up to 14 days
|
|
Nervous system disorders
Dizziness
|
12.5%
14/112 • Up to 14 days
|
|
Vascular disorders
Hypotension
|
9.8%
11/112 • Up to 14 days
|
|
Vascular disorders
Haematoma
|
5.4%
6/112 • Up to 14 days
|
|
Gastrointestinal disorders
Nausea
|
40.2%
45/112 • Up to 14 days
|
|
Gastrointestinal disorders
Vomiting
|
33.0%
37/112 • Up to 14 days
|
|
Gastrointestinal disorders
Constipation
|
9.8%
11/112 • Up to 14 days
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
20.5%
23/112 • Up to 14 days
|
|
Renal and urinary disorders
Urinary retention
|
6.2%
7/112 • Up to 14 days
|
|
General disorders
Oedema peripheral
|
8.0%
9/112 • Up to 14 days
|
|
General disorders
Pyrexia
|
6.2%
7/112 • Up to 14 days
|
|
Investigations
Haemoglobin decreased
|
9.8%
11/112 • Up to 14 days
|
|
Injury, poisoning and procedural complications
Wound haematoma
|
5.4%
6/112 • Up to 14 days
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
- Publication restrictions are in place
Restriction type: OTHER