Study to Compare the Effectiveness of Rivaroxaban (Xarelto) Versus Low-molecular-weight Heparin (LMWH) and Phenprocoumon for the Treatment and Secondary Prevention of Venous Thromboembolism in Routine Clinical Practice in Germany

Real-world Comparative Effectiveness of Rivaroxaban Versus Low-molecular-weight Heparin (LMWH) and Phenprocoumon for the Treatment and Secondary Prevention of Venous Thromboembolism (RECENT)

Researcher in this study want to compare the effectiveness of Rivaroxaban (Xarelto) versus low-molecular-weight heparin (LMWH) and phenprocoumon for the treatment and secondary prevention of venous thromboembolism by evaluating routine clinical practice data from research database in Germany. VTE is defined by a blood clot in the leg or lower extremity (deep vein thrombosis) or a blood clot in the lung (pulmonary embolism). Treatment of VTE traditionally consists of acute anticoagulation treatment with heparin (mainly LMWH), followed by maintenance oral anticoagulation with vitamin-K antagonists (in Germany mainly phenprocoumon). Rivaroxaban, a direct-acting oral anticoagulants (DOAC), is an alternative VTE treatment and has been approved for both the acute and maintenance phase of VTE treatment. The study will enroll adult male or female patients who are newly diagnosed with VTE and are already on the treatment with Rivaroxaban or LMWH and phenprocoumon. Researchers are especially interested whether patients experience under treatment any VTE events or fatal bleedings.

Study Overview

• Status: Completed
• Conditions: Venous Thromboembolism
• Intervention / Treatment: Drug: Rivaroxaban (Xarelto, BAY 59-7939); Drug: LMWH and Phenprocoumon

• Study Type: Observational
• Enrollment (Actual): 22153

Contacts and Locations

Study Locations

• Germany
  • Multiple Locations, Germany
    • Multiple facilities

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The source population of this study will include all insured members of more than 60 German statutory health insurances (SHIs) contributing data to the InGef database.

Description

Inclusion Criteria:

• At least one new diagnosis of VTE during the inclusion period:
• Ambulatory diagnosis, coded as verified,
• Primary hospital discharge diagnosis.
• Secondary hospital discharge diagnosis The quarter of the first VTE diagnosis in the inclusion period will be defined as the index quarter. For hospital diagnoses, the date of admission will be used to define the index quarter.
• The 12 months prior to the index date will define the baseline period for all included patients. Patients treated with anticoagulation regimens other than defined above (e.g. other DOACs) will not be included in the study. All patients will have to fulfill the additional inclusion criteria:
• Continuous enrolment in the baseline period
• ≥ 18 years of age at index date

Exclusion Criteria:

• A verified ambulatory or primary/ secondary hospital discharge diagnosis of VTE in the baseline period;
• A verified ambulatory or primary/ secondary hospital discharge diagnosis of atrial fibrillation in the baseline period; Individuals with documented cardiac valve surgery in the baseline period;
• A verified ambulatory or primary/ secondary hospital discharge diagnosis indicating pregnancy in the baseline period;
• A prescription of any anticoagulation treatment (heparins; vitamin-K antagonists; rivaroxaban; other DOACs) in the baseline period;
• A verified ambulatory or primary/ secondary hospital discharge diagnosis of end-stage kidney disease or a claim for dialysis in the baseline period;
• A prescription of contraindicated drug for rivaroxaban due to drug interactions (i.e. azole antifungals and HIV protease inhibitors) in the 60 days before or on the index date.
• Patients assigned to rivaroxaban exposure groups who were initially treated with a dose strength other than 15 mg or 20 mg per tablet.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Rivaroxaban; The source population of this study will include all insured members of more than 60 German statutory health insurances (SHIs) contributing data to the InGef database.	Drug: Rivaroxaban (Xarelto, BAY 59-7939); Dosage at the discretion of the treating physician
Low-molecular-weight heparin (LMWH) and Phenprocoumon; The source population of this study will include all insured members of more than 60 German statutory health insurances (SHIs) contributing data to the InGef database.	Drug: LMWH and Phenprocoumon; Dosage at the discretion of the treating physician

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk of recurrent venous thromboembolic (VTE) events in VTE patients treated with rivaroxaban compared to patients treated with LMWH and Phenprocoumon	A recurrent VTE event will be defined as a hospitalization with a primary hospital discharge diagnoses for VTE for which the admission date was >14 days after the index date. Non-interventional retrospective cohort study based on German claims data from the InGef (Institute for Applied Healthcare Research Berlin) research database between January 2013 and December 2018.	Retrospective data from January 2013 to December 2018

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk of fatal bleeding in VTE patients treated with rivaroxaban compared to patients treated with LMWH and Phenprocoumon	Cases of fatal bleeding will be defined as hospitalization with a primary hospital discharge diagnoses for bleeding with documented death as reason for hospital discharge or within 30 days after hospital discharge. Non-interventional retrospective cohort study based on German claims data from the InGef (Institute for Applied Healthcare Research Berlin) research database between January 2013 and December 2018.	Retrospective data from January 2013 to December 2018

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2020
• Primary Completion (Actual): April 30, 2021
• Study Completion (Actual): April 30, 2021

Study Registration Dates

• First Submitted: June 22, 2020
• First Submitted That Met QC Criteria: June 22, 2020
• First Posted (Actual): June 24, 2020

Study Record Updates

• Last Update Posted (Actual): April 28, 2022
• Last Update Submitted That Met QC Criteria: April 27, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Phenprocoumon
• Other Study ID Numbers: 21456

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No