A Study to Investigate Different Doses of BAY1213790 to Prevent Blood Clots in Patients Undergoing Elective Total Knee Replacement Surgery

Study Description

Brief Summary

Detailed Description

Condition or disease	Intervention/treatment	Phase
Knee Arthroplasty, Total	Drug: BAY1213790 Other Names Drug: Enoxaparin Other Names Drug: Apixaban Other Names	Phase 2

Tracking Information

First Submitted Date	September 07, 2017
Last Update Posted Date	February 12, 2018
Actual Start Date	September 21, 2017
Anticipated Completion Date	September 14, 2019
Actual Primary Completion Date	April 27, 2019
Results First Submitted Date	N/A
Received Results Disposit Date	N/A

Current Primary Outcome Measures

• Incidence of composite endpoint consisting of asymptomatic DVT as detected by mandatory bilateral venography, objectively confirmed symptomatic DVT, non-fatal PE, fatal PE, unexplained death for which PE cannot be excluded [Time Frame: up to Visit 7 (Day 12+3)]

  DVT: deep vein thrombosis PE: pulmonary embolism All suspected events will be reviewed and classified by the Central Independent Adjudication Committee

• Incidence of composite endpoint of major and clinically relevant non-major bleeding [Time Frame: up to Visit 7 (Day 12+3)]

  All suspected events will be reviewed and classified by the Central Independent Adjudication Committee

Original Primary Outcome Measures

Current Secondary Outcome Measures

• Incidence of composite endpoint of symptomatic DVT, non-fatal PE, fatal PE, unexplained death for which PE cannot be excluded up to Day 150 or objectively confirmed asymptomatic DVT up to day 12 [Time Frame: up to Visit 10 (Day 150±7)]

  All suspected events will be reviewed and classified by the Central Independent Adjudication Committee

• Incidence of composite endpoint of major and clinically relevant non-major bleeding [Time Frame: up to Visit 10 (Day 150±7)]

  All suspected events will be reviewed and classified by the Central Independent Adjudication Committee

Original Secondary Outcome Measures

Study Design

Brief Title	A Study to Investigate Different Doses of BAY1213790 to Prevent Blood Clots in Patients Undergoing Elective Total Knee Replacement Surgery
Official Title	A Randomized, Active-comparator-controlled, Multicenter Study to Assess the Safety and Efficacy of Different Doses of BAY1213790 for the Prevention of Venous Thromboembolism in Patients Undergoing Elective Primary Total Knee Arthroplasty, Open-label to Treatment and Observer-blinded to BAY1213790 Doses
Brief Summary	This study is to compare the study drug BAY1213790 to existing therapies, ie Enoxaparin or Apixaban for the prevention of blood clotting and safety in patients undergoing total knee arthroplasty (TKA). The study is open-label, but observer-blind for the different doses of BAY1213790 administered. This means that it is known which treatment is given, but it is not known which dose of BAY1213790 is administered.
Detailed Description
Study Type	Interventional
Study Phase	Phase 2
Estimated Enrollment	700
Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	Triple
Primary Purpose	Prevention
Conditions	Knee Arthroplasty, Total
Target Follow-Up Duration	N/A
Biospecimen:	N/A
Sampling Method	N/A
Study Population	N/A
Intervention	Drug: BAY1213790 single dose intravenous infusion Other Names Drug: Enoxaparin daily subcutaneous injection Other Names Drug: Apixaban twice daily oral administration Other Names
Study Groups/Cohorts	BAY1213790 pre and post surgery Post-surgery administration part (A): Single infusion in the morning following the day of Total Knee Arthroplasty (TKA) Pre-surgery administration part (B): Single infusion in the second half of the day before Total Knee Arthroplasty (TKA) Enoxaparin for at least 10 days Started either in the evening before TKA or 6-8 hours after TKA (at investigator's discretion), followed by once daily subcutaneous injections for at least 10 days and until venography is performed Apixaban for at least 10 days For at least 10 days post-surgery and until venography is performed, starting within 12 to 24 hours after TKA surgery
Study Arms	Active Comparator Apixaban for at least 10 days For at least 10 days post-surgery and until venography is performed, starting within 12 to 24 hours after TKA surgery Drug : Apixaban twice daily oral administration Experimental BAY1213790 pre and post surgery Post-surgery administration part (A): Single infusion in the morning following the day of Total Knee Arthroplasty (TKA) Pre-surgery administration part (B): Single infusion in the second half of the day before Total Knee Arthroplasty (TKA) Drug : BAY1213790 single dose intravenous infusion Active Comparator Enoxaparin for at least 10 days Started either in the evening before TKA or 6-8 hours after TKA (at investigator's discretion), followed by once daily subcutaneous injections for at least 10 days and until venography is performed Drug : Enoxaparin daily subcutaneous injection

Arm	Intervention/Treatment
Active Comparator Apixaban for at least 10 days For at least 10 days post-surgery and until venography is performed, starting within 12 to 24 hours after TKA surgery	Drug : Apixaban twice daily oral administration
Experimental BAY1213790 pre and post surgery Post-surgery administration part (A): Single infusion in the morning following the day of Total Knee Arthroplasty (TKA) Pre-surgery administration part (B): Single infusion in the second half of the day before Total Knee Arthroplasty (TKA)	Drug : BAY1213790 single dose intravenous infusion
Active Comparator Enoxaparin for at least 10 days Started either in the evening before TKA or 6-8 hours after TKA (at investigator's discretion), followed by once daily subcutaneous injections for at least 10 days and until venography is performed	Drug : Enoxaparin daily subcutaneous injection

Recruitment Information

Recruitment Status:	Recruiting
Enrollment	700
Completion Date	September 14, 2019
Eligibility Criteria:	Inclusion Criteria: - Patients aged ≥18 years undergoing elective primary, unilateral TKA For women, - Women of non-childbearing potential Exclusion Criteria: - High risk for clinically significant bleeding - Prior deep vein thrombosis - Creatinine clearance below 60 ml/min - Active cancer except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been curatively treated - Contraindication listed in the local label of the comparator treatments - Requirement for full dose anticoagulation or dual antiplatelet therapy (low dose of acetylsalicylic acid is allowed)
Gender	All
Age	18 Years to N/A
Accepts Healthy Volunteers	No
Contacts	Bayer Clinical Trials Contact +4930300139003 [email protected]
Listed Location Countries	Bulgaria Canada Czechia Germany Greece Israel Latvia Lithuania Poland Portugal Russian Federation South Africa Spain Ukraine Hungary

Administrative Information

NCT Number:	NCT03276143
Other Study ID Numbers	17664 2016-002681-31
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: No Studies a U.S. FDA-regulated Device Product: No Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement	Not Available
Responsible Party	,
Study Sponsor	Bayer
Collaborators	Not Available
Investigators	Study Director Bayer Study Director Bayer