Trial Outcomes & Findings for Factor Xa Inhibitor, PRT054021, Against Enoxaparin for the Prevention of Venous Thromboembolic Events (EXPERT) (NCT NCT00375609)

Last Updated: 2023-08-07

Results Overview

Incidence of adjudicated venous thromboembolism (VTE) through Day 10-14 following TKR where VTE is defined as DVT (proximal and/or distal) and/or PE. Patients were evaluated for VTE daily while hospitalized and were contacted every 2 to 4 days after discharge and before the day of the mandatory venogram to monitor for study endpoints

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

215 participants

Primary outcome timeframe

Through Day 10-14 following TKR surgery, at time of mandatory venogram

Results posted on

2023-08-07

Participant Flow

Between 10 May 2006 and 12 February 2007, 215 patients were enrolled. After undergoing unilateral total knee replacement surgery, patients were randomized to 1 of 3 treatment groups (2:2:1 allocation). The study was open-label for randomization to enoxaparin versus betrixaban, but the 15 mg versus 40 mg dose of betrixaban was double-blind.

Patients scheduled to undergo elective primary unilateral total knee replacement (TKR) surgery were evaluated for eligibility 1 to 30 days before surgery (Screening). Consenting subjects who remained eligible for the study after TKR were randomized. 215 patients were randomized and all but 1 received at least 1 dose of study drug.

Participant milestones

Participant milestones
Measure	Betrixaban 15 mg Betrixaban 15 mg oral twice daily for 10 to 14 days	Betrixaban 40 mg Betrixaban 40 mg oral twice daily for 10 to 14 days	Enoxaparin Enoxaparin 30 mg administered subcutaneously every 12 hours for 10 to 14 days
Overall Study STARTED	88	84	43
Overall Study COMPLETED	84	77	42
Overall Study NOT COMPLETED	4	7	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Betrixaban 15 mg Betrixaban 15 mg oral twice daily for 10 to 14 days	Betrixaban 40 mg Betrixaban 40 mg oral twice daily for 10 to 14 days	Enoxaparin Enoxaparin 30 mg administered subcutaneously every 12 hours for 10 to 14 days
Overall Study Did not receive treatment	1	0	0
Overall Study Adverse Event	0	3	0
Overall Study Lost to Follow-up	1	0	0
Overall Study Physician Decision	0	0	1
Overall Study Withdrawal by Subject	1	4	0
Overall Study Neurologist Wanted Pt to start Plavix	1	0	0

Baseline Characteristics

Factor Xa Inhibitor, PRT054021, Against Enoxaparin for the Prevention of Venous Thromboembolic Events (EXPERT)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Betrixaban 15 mg n=87 Participants Betrixaban 15 mg oral twice daily for 10 to 14 days	Betrixaban 40 mg n=84 Participants Betrixaban 40 mg oral twice daily for 10 to 14 days	Enoxaparin n=43 Participants Enoxaparin 30 mg administered subcutaneously every 12 hours for 10 to 14 days	Total n=214 Participants Total of all reporting groups
Age, Continuous	63.3 years STANDARD_DEVIATION 7.2 • n=5 Participants	65.0 years STANDARD_DEVIATION 7.9 • n=7 Participants	61.9 years STANDARD_DEVIATION 9.6 • n=5 Participants	63.7 years STANDARD_DEVIATION 8.1 • n=4 Participants
Sex: Female, Male Female	55 Participants n=5 Participants	52 Participants n=7 Participants	22 Participants n=5 Participants	129 Participants n=4 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	32 Participants n=7 Participants	21 Participants n=5 Participants	85 Participants n=4 Participants

PRIMARY outcome

Timeframe: Through Day 10-14 following TKR surgery, at time of mandatory venogram

Population: All randomized patients who took at least 1 dose of study medication after randomization and for whom an evaluable venogram was available

Outcome measures

Outcome measures
Measure	Betrixaban 15 mg n=70 Participants Betrixaban 15 mg oral twice daily for 10 to 14 days	Betrixaban 40 mg n=65 Participants Betrixaban 40 mg oral twice daily for 10 to 14 days	Enoxaparin n=40 Participants Enoxaparin 30 mg administered subcutaneously every 12 hours for 10 to 14 days
Incidence of Adjudicated Venous Thromboembolism (VTE)	20 Percentage of Participants Interval 11.4 to 31.3	15.4 Percentage of Participants Interval 7.6 to 26.5	10 Percentage of Participants Interval 2.8 to 23.7

PRIMARY outcome

Timeframe: Through follow-up at approximately 6 (±2) weeks after TKR surgery

Population: All randomized patients who took at least 1 dose of study medication after randomization.

The incidence of adjudicated major and clinical relevant non-major bleeding. Major bleeding was defined as fatal, involving vital organs, requiring additional surgery or a new therapeutic procedure, or a bleeding index \>=2. Bleeding Index was defined as the number of units of packed red blood cells or whole blood transfused plus the haemoglobin values before the bleeding episode minus the haemoglobin values after the bleed had stabilized (in g/dL)

Outcome measures

Outcome measures
Measure	Betrixaban 15 mg n=87 Participants Betrixaban 15 mg oral twice daily for 10 to 14 days	Betrixaban 40 mg n=84 Participants Betrixaban 40 mg oral twice daily for 10 to 14 days	Enoxaparin n=43 Participants Enoxaparin 30 mg administered subcutaneously every 12 hours for 10 to 14 days
Incidence of Adjudicated Overt Bleeding Events: Primary Safety Endpoint	0 Percentage of Participants Interval 0.0 to 4.2	2.4 Percentage of Participants Interval 0.3 to 8.3	7.0 Percentage of Participants Interval 1.5 to 19.1

SECONDARY outcome

Timeframe: At follow-up at approximately 6 (±2) weeks after TKR surgery

Population: All randomized patients who took at least 1 dose of study medication after randomization and for whom an evaluable venogram was available

Incidence of adjudicated pulmonary embolism (PE) and all deep vein thrombosis (DVT) (proximal and distal) through the time of venography on Day 10 to 14 and at follow-up at approximately 6 (±2) weeks after TKR surgery

Outcome measures

Outcome measures
Measure	Betrixaban 15 mg n=70 Participants Betrixaban 15 mg oral twice daily for 10 to 14 days	Betrixaban 40 mg n=65 Participants Betrixaban 40 mg oral twice daily for 10 to 14 days	Enoxaparin n=40 Participants Enoxaparin 30 mg administered subcutaneously every 12 hours for 10 to 14 days
Incidence of Adjudicated Pulmonary Embolism (PE) and All Deep Vein Thrombosis (DVT) (Proximal and Distal)	20 Percentage of Participants Interval 11.4 to 31.3	15.4 Percentage of Participants Interval 7.6 to 26.5	12.5 Percentage of Participants Interval 4.2 to 26.8

Adverse Events

Betrixaban 15 mg

Serious events: 3 serious events

Other events: 83 other events

Deaths: 0 deaths

Betrixaban 40 mg

Serious events: 6 serious events

Other events: 80 other events

Deaths: 0 deaths

Enoxaparin

Serious events: 1 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Betrixaban 15 mg n=87 participants at risk Betrixaban 15 mg oral twice daily for 10 to 14 days	Betrixaban 40 mg n=84 participants at risk Betrixaban 40 mg oral twice daily for 10 to 14 days	Enoxaparin n=43 participants at risk Enoxaparin 30 mg administered subcutaneously every 12 hours for 10 to 14 days
Infections and infestations Sepsis	1.1% 1/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Infections and infestations Arthritis bacterial	0.00% 0/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	1.2% 1/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Infections and infestations Cellulitis	0.00% 0/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	1.2% 1/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Psychiatric disorders Delirium	1.1% 1/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Vascular disorders Haematoma	1.1% 1/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Injury, poisoning and procedural complications Procedural pain	0.00% 0/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	1.2% 1/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Cardiac disorders Atrial fibrillation	0.00% 0/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	1.2% 1/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Gastrointestinal disorders Hiatus hernia	0.00% 0/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	1.2% 1/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Renal and urinary disorders Acute renal failure	0.00% 0/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	1.2% 1/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	2.3% 1/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class

Other adverse events

Additional Information

Head of Clinical Development

Portola Pharmaceuticals, Inc.

Phone: 650-246-7000

Results disclosure agreements

Principal investigator is a sponsor employee Due to multiple studies, centers and countries this will vary.
Publication restrictions are in place

Restriction type: OTHER

Measure	Betrixaban 15 mg n=87 participants at risk Betrixaban 15 mg oral twice daily for 10 to 14 days	Betrixaban 40 mg n=84 participants at risk Betrixaban 40 mg oral twice daily for 10 to 14 days	Enoxaparin n=43 participants at risk Enoxaparin 30 mg administered subcutaneously every 12 hours for 10 to 14 days
Injury, poisoning and procedural complications Procedural pain	59.8% 52/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	51.2% 43/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	7.0% 3/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Gastrointestinal disorders Nausea	36.8% 32/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	45.2% 38/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	16.3% 7/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Gastrointestinal disorders Constipation	29.9% 26/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	21.4% 18/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	18.6% 8/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Investigations Body temperature	18.4% 16/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	19.0% 16/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	18.6% 8/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Gastrointestinal disorders Vomiting	13.8% 12/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	15.5% 13/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	2.3% 1/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
General disorders Pyrexia	6.9% 6/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	15.5% 13/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	7.0% 3/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
General disorders OEDEMA PERIPHERAL	5.7% 5/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	13.1% 11/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	9.3% 4/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Metabolism and nutrition disorders HYPOKALAEMIA	10.3% 9/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	11.9% 10/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	2.3% 1/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Blood and lymphatic system disorders ANAEMIA	9.2% 8/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	10.7% 9/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	2.3% 1/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Vascular disorders HYPOTENSION	6.9% 6/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	9.5% 8/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	2.3% 1/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Skin and subcutaneous tissue disorders PRURITUS	11.5% 10/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	7.1% 6/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Investigations HAEMOGLOBIN DECREASED	5.7% 5/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	7.1% 6/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	7.0% 3/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Injury, poisoning and procedural complications POSTOPERATIVE FEVER	9.2% 8/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	6.0% 5/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	7.0% 3/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Psychiatric disorders INSOMNIA	16.1% 14/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	4.8% 4/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	11.6% 5/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Gastrointestinal disorders DYSPEPSIA	5.7% 5/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	4.8% 4/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Respiratory, thoracic and mediastinal disorders RESPIRATORY GAS EXCHANGE DISORDER	0.00% 0/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	4.8% 4/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
General disorders LOCAL SWELLING	10.3% 9/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	3.6% 3/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	2.3% 1/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Nervous system disorders DIZZINESS	5.7% 5/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	3.6% 3/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	4.7% 2/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Investigations BLOOD POTASSIUM DECREASED	2.3% 2/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	3.6% 3/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	4.7% 2/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Injury, poisoning and procedural complications WOUND SECRETION	2.3% 2/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	3.6% 3/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	4.7% 2/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Skin and subcutaneous tissue disorders RASH	1.1% 1/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	3.6% 3/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	4.7% 2/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Gastrointestinal disorders DIARRHOEA	1.1% 1/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	3.6% 3/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	2.3% 1/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	1.1% 1/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	3.6% 3/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	2.3% 1/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Cardiac disorders SINUS TACHYCARDIA	1.1% 1/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	3.6% 3/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Respiratory, thoracic and mediastinal disorders ATELECTASIS	0.00% 0/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	3.6% 3/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Investigations ELECTROCARDIOGRAM QT PROLONGED	0.00% 0/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	3.6% 3/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Injury, poisoning and procedural complications INCISION SITE ERYTHEMA	0.00% 0/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	3.6% 3/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Respiratory, thoracic and mediastinal disorders RALES	4.6% 4/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	2.4% 2/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	2.3% 1/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Injury, poisoning and procedural complications PROCEDURAL NAUSEA	6.9% 6/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	1.2% 1/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	2.3% 1/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Nervous system disorders HEADACHE	3.4% 3/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	1.2% 1/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	4.7% 2/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Investigations BREATH SOUNDS ABNORMAL	3.4% 3/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	1.2% 1/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Investigations ALANINE AMINOTRANSFERASE INCREASED	2.3% 2/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	1.2% 1/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	7.0% 3/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Psychiatric disorders ANXIETY	2.3% 2/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	1.2% 1/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	4.7% 2/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Investigations OXYGEN SATURATION DECREASED	4.6% 4/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Skin and subcutaneous tissue disorders BLISTER	3.4% 3/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	2.3% 1/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Skin and subcutaneous tissue disorders ERYTHEMA	3.4% 3/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Investigations PLATELET COUNT INCREASED	0.00% 0/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	7.0% 3/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class
Investigations BLOOD ALKALINE PHOSPHATASE INCREASED	0.00% 0/87 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	0.00% 0/84 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class	4.7% 2/43 • Through follow-up at approximately 6 (±2) weeks after TKR surgery Serious adverse events by system organ class