Rivaroxaban in the Treatment of Venous Thromboembolism (VTE) in Cancer Patients

CONKO_011/ AIO-SUP-0115/Ass.: Rivaroxaban in the Treatment of Venous Thromboembolism (VTE) in Cancer Patients - a Randomized Phase III Study

The purpose of this study is to show feasibility (efficacy and safety) of Rivaroxaban in the treatment of VTE in cancer patients in comparison to the standard treatment with low molecular weight heparin (LMWH).

Tumor patients with active cancer and newly diagnosed thromboembolic events are randomised to receive either Rivaroxaban or the standard treatment with low-molecular heparin.

Study Overview

• Status: Terminated
• Conditions: Cancer; Venous Thromboembolism
• Intervention / Treatment: Drug: Rivaroxaban; Drug: low-molecular heparine

• Study Type: Interventional
• Enrollment (Actual): 246
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany, 52074
    • Uniklinik

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Newly diagnosed and objectively confirmed acute venous thromboembolism
• Active malignancy
• Life expectancy of at least 6 months
• Performance-Status according to Karnofsky Performance Scale ≥ 70 %
• Patient's compliance and geographical situation allowing an adequate follow up
• platelets ≥ 100.000 /μl, INR < 1.5, PTT < 40 sec.
• written informed consent of the patient prior to any procedure in connection with the study
• male and female patients with an age of at least 18 years

Exclusion Criteria:

• therapeutic anticoagulation > 96 hours prior to study treatment
• known allergic reactions against the study drugs or the substances included therein
• known conditions associated with high risk of bleeding, known history of hemorrhagic diathesis
• acute clinically relevant bleeding in the last 2 weeks
• any history of spontaneous major/cerebral bleeding
• history of heparin induced thrombocytopenia II
• pregnant or breast-feeding women. Women of child-bearing potential must have a negative pregnancy test performed < 7 days prior to start of the treatment
• severe renal insufficiency (GFR < 30 ml/min)
• liver disease with coagulation impairment, including Child B and C
• cirrhosis
• acute medical illness
• treatment of the underlying cancer with experimental therapies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rivaroxaban; Arm A: Rivaroxaban	Drug: Rivaroxaban; Rivaroxaban 15 mg twice daily for 21 days, followed by 20 mg once daily over a period of 3 months; Other Names: Xarelto
Active Comparator: low-molecular heparine; Arm B: standard treatment with low-molecular heparine	Drug: low-molecular heparine; LMWH in therapeutic dosage (1-2× daily s.c.) according to standards of the individual study center, using licensed dosages, e.g.; Enoxaparin 1 mg/kg BW twice daily; Tinzaparin 175 I.E./kg BW once daily; Dalteparin 200 I.E./kg BW once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Patient-reported treatment satisfaction (convenience) with Rivaroxaban in the treatment of acute VTE in cancer patients in comparison with the standard treatment with low molecular weight heparin	From randomization to 4 weeks after treatment start

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of symptomatic venous thrombembolism-recurrence within 3 months exploratory analysis for patients with treatment	From randomization to 3 months after treatment start
Exploratory analysis for "time on treatment"	From randomization to 12 weeks after treatment start
Subgroup analysis with regard to rate of Pulmonary embolism, venous thrombembolism recurrence and bleedings (major, clinically relevant, minor) according to stratification characteristics	From randomization to end of follow up (up to 24 weeks)
Rate of myocardial infarction and ischemic stroke	From randomization to end of follow up (up to 24 weeks)
Compliance of patients (adherence)	From randomization to end of follow up (up to 24 weeks)
Overall mortality 3 and 6 months after randomization	From randomization to 3 and 6 months after randomization
Quality of Life (Spitzer Index (Spitzer 1981), Anticlot Treatment Scale (ACTS) and TSQM	4 weekly, up to 12 weeks
Rate of clinically relevant bleeding (major + clinically relevant non major) within 3 months	From randomization to 3 months after randomization
Rate of minor bleedings within 3 months	From randomization to 3 months after randomization

Collaborators and Investigators

• Sponsor: AIO-Studien-gGmbH
• Collaborators: Bayer; Charite University, Berlin, Germany

Publications and helpful links

General Publications

• Riaz IB, Fuentes HE, Naqvi SAA, He H, Sipra QR, Tafur AJ, Padranos L, Wysokinski WE, Marshall AL, Vandvik PO, Montori V, Bryce AH, Liu H, Badgett RG, Murad MH, McBane RD 2nd. Direct Oral Anticoagulants Compared With Dalteparin for Treatment of Cancer-Associated Thrombosis: A Living, Interactive Systematic Review and Network Meta-analysis. Mayo Clin Proc. 2022 Feb;97(2):308-324. doi: 10.1016/j.mayocp.2020.10.041. Epub 2021 Jun 22.

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2016
• Primary Completion (Actual): June 11, 2019
• Study Completion (Actual): August 19, 2019

Study Registration Dates

• First Submitted: October 15, 2015
• First Submitted That Met QC Criteria: October 21, 2015
• First Posted (Estimate): October 22, 2015

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 28, 2021
• Last Verified: April 1, 2021

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
• Other Study ID Numbers: CONKO-011 AIO-SUP-0115/ass.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No