Trial Outcomes & Findings for Pradaxa (Dabigatran Etexilate) VTE Prevention After Elective Total Hip or Knee Replacement Surgery (NCT NCT01153698)

NCT ID: NCT01153698

Last Updated: 2023-10-03

Results Overview

Major bleeding events were defined according to the modified McMaster criteria. The criteria for MBEs were: fatal; clinically overt associated with loss of haemoglobin \>=20g/L 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.

• Recruitment status: TERMINATED
• Target enrollment: 167 participants
• Primary outcome timeframe: From last enoxaparin administration until 24 hours after last Pradaxa intake( planned: knee replacement: Day 10 after surgery, hip replacement:Day 28-35 after surgery)
• Results posted on: 2023-10-03

Participant Flow

There were 168 patients enrolled and treated. 161 of these patients received enoxaparin and switched to dabigatran etexilate (Pradaxa), 2 patients were only treated with dabigatran etexilate and 5 patients only received enoxaparin but did not switch to dabigatran etexilate.

Participant milestones

Measure	All Patients receiving at least one dose of enoxaparin 40mg or at least one dose of Pradaxa 220mg
Overall Study STARTED	168
Overall Study COMPLETED	139
Overall Study NOT COMPLETED	29

Reasons for withdrawal

Measure	All Patients receiving at least one dose of enoxaparin 40mg or at least one dose of Pradaxa 220mg
Overall Study Adverse Event	12
Overall Study Lost to Follow-up	4
Overall Study Withdrawal by Subject	2
Overall Study Switch to other anticoagulants	4
Overall Study Other	2
Overall Study Not treated with Pradaxa	5

Baseline Characteristics

Pradaxa (Dabigatran Etexilate) VTE Prevention After Elective Total Hip or Knee Replacement Surgery

Baseline characteristics by cohort

Measure	All Patients n=168 Participants receiving at least one dose of enoxaparin 40mg or at least one dose of Pradaxa 220mg
Age, Continuous	60.9 Years STANDARD_DEVIATION 9.2 • n=5 Participants
Sex: Female, Male Female	96 Participants n=5 Participants
Sex: Female, Male Male	72 Participants n=5 Participants

PRIMARY outcome

Timeframe: From last enoxaparin administration until 24 hours after last Pradaxa intake( planned: knee replacement: Day 10 after surgery, hip replacement:Day 28-35 after surgery)

Population: Treated set (TS) reduced to patients with switch-/ post-switch period. TS includes all patients who received at least one dose of enoxaparin or at least one dose of Pradaxa.

Major bleeding events were defined according to the modified McMaster criteria. The criteria for MBEs were: fatal; clinically overt associated with loss of haemoglobin >=20g/L 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.

Outcome measures

Measure	All Patients n=163 Participants receiving at least one dose of enoxaparin 40mg or at least one dose of Pradaxa 220mg
Percentage of Patients With Major Bleeding Events (MBE) During the Switch-/ Post-switch Treatment Period	0.61 Percentage of participants Interval 0.02 to 3.37

PRIMARY outcome

Timeframe: From last enoxaparin administration until 24 hours after last Pradaxa intake (planned: knee replacement: Day 10 after surgery, hip replacement:Day 28-35 after surgery)

Population: TS reduced to patients with switch-/ post-switch period.

sVTE was defined as the composite of documented symptomatic proximal and distal deep vein thrombosis (DVT) and documented symptomatic non-fatal pulmonary embolism (PE).

Outcome measures

Measure	All Patients n=163 Participants receiving at least one dose of enoxaparin 40mg or at least one dose of Pradaxa 220mg
Percentage of Patients With Symptomatic Venous Thromboembolic Events (sVTE) and All-cause Mortality Events During the Switch-/ Post-switch Treatment Period	0 Percentage of participants Interval 0.0 to 2.24

SECONDARY outcome

Timeframe: From first enoxaparin administration until 24 hours after last Pradaxa intake if switch to Pradaxa was performed or to 35 hours after last enoxaparin administration if no switch was performed

Population: TS

MBEs were defined according to the modified McMaster criteria. The criteria for MBEs were: fatal; clinically overt associated with loss of haemoglobin >=20g/L 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.

Outcome measures

Measure	All Patients n=168 Participants receiving at least one dose of enoxaparin 40mg or at least one dose of Pradaxa 220mg
Percentage of Patients With MBE During Total Treatment Period	0.60 Percentage of participants Interval 0.02 to 3.27

SECONDARY outcome

Timeframe: From first enoxaparin administration until last enoxaparin administration

Population: TS reduced to patients with pre-switch period.

MBEs were defined according to the modified McMaster criteria. The criteria for MBEs were: fatal; clinically overt associated with loss of haemoglobin >=20g/L 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.

Outcome measures

Measure	All Patients n=166 Participants receiving at least one dose of enoxaparin 40mg or at least one dose of Pradaxa 220mg
Percentage of Patients With MBE During Pre-switch Treatment Period	0 Percentage of participants Interval 0.0 to 2.2

SECONDARY outcome

Timeframe: From first enoxaparin administration until 24 hours after last Pradaxa intake if switch to Pradaxa was performed or to 35 hours after last enoxaparin administration if no switch was performed

Population: TS

sVTE was defined as the composite of documented symptomatic proximal and distal DVT and documented symptomatic non-fatal PE.

Outcome measures

Measure	All Patients n=168 Participants receiving at least one dose of enoxaparin 40mg or at least one dose of Pradaxa 220mg
Percentage of Patients With sVTE and All-cause Mortality Events During Total Treatment Period	0 Percentage of participants Interval 0.0 to 2.17

SECONDARY outcome

Timeframe: From first enoxaparin administration until last enoxaparin administration

Population: TS reduced to patients with pre-switch period.

sVTE was defined as the composite of documented symptomatic proximal and distal DVT and documented symptomatic non-fatal PE.

Outcome measures

Measure	All Patients n=166 Participants receiving at least one dose of enoxaparin 40mg or at least one dose of Pradaxa 220mg
Percentage of Patients With sVTE and All-cause Mortality Events During Pre-switch Treatment Period	0 Percentage of participants Interval 0.0 to 2.2

SECONDARY outcome

Timeframe: From last enoxaparin administration until first Pradaxa intake

Population: TS reduced to patients with switch period.

sVTE was defined as the composite of documented symptomatic proximal and distal DVT and documented symptomatic non-fatal PE.

Symptomatic DVT is defined as clinically symptomatic venous thromboembolic event and symptomatic non-fatal PE is defined as symptomatic pulmonary embolism

Outcome measures

Measure	All Patients n=161 Participants receiving at least one dose of enoxaparin 40mg or at least one dose of Pradaxa 220mg
Percentage of Patients With sVTE and All-cause Mortality Events During Switch Treatment Period	0 Percentage of participants Interval 0.0 to 2.27

SECONDARY outcome

Timeframe: From first enoxaparin administration until 24 hours after last Pradaxa intake if switch to Pradaxa was performed or to 35 hours after last enoxaparin administration if no switch was performed

Population: TS

Major extra-surgical site bleedings include all major bleedings not occurred at surgical site

Outcome measures

Measure	All Patients n=168 Participants receiving at least one dose of enoxaparin 40mg or at least one dose of Pradaxa 220mg
Percentage of Patients With Major Extra-surgical Site Bleedings During Total Treatment Period	0 Percentage of participants Interval 0.0 to 2.17

SECONDARY outcome

Timeframe: From end of surgery (before first dosing) until 24 hours after last Pradaxa intake

Population: Treated Set (All patients with non-missing information for both, the volume drainage until first dose of Pradaxa and the volume drainage from first dose of Pradaxa and onwards).

Total volume of wound drainage is calculated as sum of volume drainage from end of surgery until first dose of Pradaxa plus volume drainage from first dose of Pradaxa and onwards.

Outcome measures

Measure	All Patients n=129 Participants receiving at least one dose of enoxaparin 40mg or at least one dose of Pradaxa 220mg
Volume of Wound Drainage (Post-operative)	462.1 ml Standard Deviation 275.2

SECONDARY outcome

Timeframe: From first enoxaparin administration until 24 hours after last Pradaxa intake ( planned: knee replacement: Day 10 after surgery, hip replacement:Day 28-35 after surgery)

Population: Treated Set

Total treatment period is defined from first enoxaparin administration to 24h after last Pradaxa intake or to 35h after last enoxaparin administration if no switch was performed.

Outcome measures

Measure	All Patients n=168 Participants receiving at least one dose of enoxaparin 40mg or at least one dose of Pradaxa 220mg
Percentage of Patients With Single Components of Composite of sVTE and All-cause Mortality Events During Total Treatment Period Documented symptomatic proximal DVT	0 Number of participants
Percentage of Patients With Single Components of Composite of sVTE and All-cause Mortality Events During Total Treatment Period Documented symptomatic distal DVT	0 Number of participants
Percentage of Patients With Single Components of Composite of sVTE and All-cause Mortality Events During Total Treatment Period Documented symptomatic non-fatal PE	0 Number of participants
Percentage of Patients With Single Components of Composite of sVTE and All-cause Mortality Events During Total Treatment Period All-cause mortality	0 Number of participants

Adverse Events

Enoxaparin 40mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Pradaxa 220mg

Serious events: 4 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Measure	Enoxaparin 40mg n=166 participants at risk All patients treated with enoxaparin	Pradaxa 220mg n=163 participants at risk All patients treated with Pradaxa
Infections and infestations Pneumonia	0.00% 0/166 • Enoxaparin 40mg: From first enoxaparin administration until first Pradaxa intake (if switch was performed) otherwise until 35h after last Enoxaparin administration; Pradaxa 220mg: From first Pradaxa intake until 24h after last Pradaxa intake	0.61% 1/163 • Enoxaparin 40mg: From first enoxaparin administration until first Pradaxa intake (if switch was performed) otherwise until 35h after last Enoxaparin administration; Pradaxa 220mg: From first Pradaxa intake until 24h after last Pradaxa intake
Cardiac disorders Myocardial infarction	0.00% 0/166 • Enoxaparin 40mg: From first enoxaparin administration until first Pradaxa intake (if switch was performed) otherwise until 35h after last Enoxaparin administration; Pradaxa 220mg: From first Pradaxa intake until 24h after last Pradaxa intake	0.61% 1/163 • Enoxaparin 40mg: From first enoxaparin administration until first Pradaxa intake (if switch was performed) otherwise until 35h after last Enoxaparin administration; Pradaxa 220mg: From first Pradaxa intake until 24h after last Pradaxa intake
Renal and urinary disorders Renal failure	0.00% 0/166 • Enoxaparin 40mg: From first enoxaparin administration until first Pradaxa intake (if switch was performed) otherwise until 35h after last Enoxaparin administration; Pradaxa 220mg: From first Pradaxa intake until 24h after last Pradaxa intake	0.61% 1/163 • Enoxaparin 40mg: From first enoxaparin administration until first Pradaxa intake (if switch was performed) otherwise until 35h after last Enoxaparin administration; Pradaxa 220mg: From first Pradaxa intake until 24h after last Pradaxa intake
General disorders Device dislocation	0.00% 0/166 • Enoxaparin 40mg: From first enoxaparin administration until first Pradaxa intake (if switch was performed) otherwise until 35h after last Enoxaparin administration; Pradaxa 220mg: From first Pradaxa intake until 24h after last Pradaxa intake	0.61% 1/163 • Enoxaparin 40mg: From first enoxaparin administration until first Pradaxa intake (if switch was performed) otherwise until 35h after last Enoxaparin administration; Pradaxa 220mg: From first Pradaxa intake until 24h after last Pradaxa intake
Investigations Hepatic enzyme increased	0.00% 0/166 • Enoxaparin 40mg: From first enoxaparin administration until first Pradaxa intake (if switch was performed) otherwise until 35h after last Enoxaparin administration; Pradaxa 220mg: From first Pradaxa intake until 24h after last Pradaxa intake	0.61% 1/163 • Enoxaparin 40mg: From first enoxaparin administration until first Pradaxa intake (if switch was performed) otherwise until 35h after last Enoxaparin administration; Pradaxa 220mg: From first Pradaxa intake until 24h after last Pradaxa intake

Other adverse events

Measure	Enoxaparin 40mg n=166 participants at risk All patients treated with enoxaparin	Pradaxa 220mg n=163 participants at risk All patients treated with Pradaxa
Injury, poisoning and procedural complications Seroma	0.00% 0/166 • Enoxaparin 40mg: From first enoxaparin administration until first Pradaxa intake (if switch was performed) otherwise until 35h after last Enoxaparin administration; Pradaxa 220mg: From first Pradaxa intake until 24h after last Pradaxa intake	8.6% 14/163 • Enoxaparin 40mg: From first enoxaparin administration until first Pradaxa intake (if switch was performed) otherwise until 35h after last Enoxaparin administration; Pradaxa 220mg: From first Pradaxa intake until 24h after last Pradaxa intake

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

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