Cancer Venous Thromboembolism (VTE)

• ClinicalTrials.gov Identifier: NCT02073682
• Recruitment Status: Completed
• First Posted: February 27, 2014
• Results First Posted: October 24, 2018
• Last Update Posted: March 6, 2019
• Sponsor: Daiichi Sankyo, Inc.
• Information provided by (Responsible Party): Daiichi Sankyo, Inc.

Study Description

Brief Summary:

The primary objective is to demonstrate the non-inferiority of edoxaban (preceded by a short course of LMWH) compared with dalteparin for the prevention of the combined outcome of recurrent venous thromboembolism (VTE) or major bleeding in subjects with VTE associated with cancer during a 12-month study period. If non-inferiority is established, LMWH/edoxaban will be compared with dalteparin for superiority.

Condition or disease	Intervention/treatment	Phase
Venous Thromboembolism (VTE); Deep Vein Thrombosis (DVT); Pulmonary Embolism (PE); Cancer	Drug: Edoxaban; Drug: Dalteparin; Drug: Low molecular weight heparin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1046 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3b, Prospective, Randomized, Open-label, Blind Evaluator (PROBE) Study Evaluating the Efficacy and Safety of (LMW) Heparin/Edoxaban Versus Dalteparin in Venous Thromboembolism Associated With Cancer
• Actual Study Start Date: July 16, 2015
• Actual Primary Completion Date: September 15, 2017
• Actual Study Completion Date: September 15, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Edoxaban group; After 5 days of low molecular weight heparin (LMWH), patients receive edoxaban treatment daily - tablet for oral use	Drug: Edoxaban; After the 5 day treatment with LMWH, patients receive edoxaban 60 mg once daily (QD) as 2 × 30 mg tablets (or 1 x 30 mg tablet QD for patients requiring dose adjustment) for the remainder of the treatment period.; Other Name: DU-176b; Drug: Low molecular weight heparin; Therapeutic doses of subcutaneous LMWH were administered for at least 5 days (to patients in the edoxaban group); this 5-day period may have included the pre-randomization LMWH (if applicable). The choice of parenteral LMWH was up to the treating physician.; Other Name: LMWH
Active Comparator: Dalteparin group; Participants receive Dalteparin treatment daily -solution for subcutaneous injection	Drug: Dalteparin; Dalteparin was administered via subcutaneous injection at a dose of 200 IU/kg (maximum daily dose 18,000 IU) for 30 days, and at a dose of 150 IU/kg from Day 31 to the end of treatment.; Other Name: Active comparator

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Adjudicated Recurrent Venous Thromboembolism (VTE) or Major Bleeding Event [ Time Frame: 12 months ]

Secondary Outcome Measures :

1. Number of Participants With Adjudicated Major Bleeding Events While on Treatment [ Time Frame: 12 months ]
   The primary safety endpoint was major bleeding events during the On-Treatment Study Period (defined as on-study drug or up to 3 days after the last dose of study drug).
2. Number of Participants With Recurrent Venous Thromboembolism (VTE) During the Overall Study Period [ Time Frame: 12 months ]
3. Number of Participants With Recurrent Deep Vein Thrombosis (DVT) During the Overall Study Period [ Time Frame: 12 months ]
4. Number of Participants With Recurrent Non-Fatal Pulmonary Embolism (PE) During the Overall Study Period [ Time Frame: 12 months ]
5. Number of Participants With VTE-Related Death [ Time Frame: 12 months ]
6. Number of Participants With Recurrent VTE, Major Bleed or All-Cause Death [ Time Frame: 12 months ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Male or female subjects with age ≥ 18 years or the otherwise legal lower age according to the country of residence;
• Confirmed acute lower extremity proximal DVT or PE for which long term treatment with low molecular weight heparin (LMWH) is indicated;
• Cancer, other than basal-cell or squamous-cell carcinoma of the skin;
• Able to provide written informed consent.

Exclusion Criteria:

• Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current (index) episode of DVT and/or PE;
• Treatment with therapeutic doses of an anticoagulant other than that used for pretreatment of the current (index) VTE episode prior to randomization;
• Active bleeding or high risk for bleeding contraindicating treatment with LMWH or edoxaban;
• Any other contraindication listed in the local labeling of dalteparin, enoxaparin, or edoxaban;

Contacts and Locations

Locations

United States, Florida

Brandon, Florida, United States

United States, Georgia

Jonesboro, Georgia, United States

United States, Michigan

Detroit, Michigan, United States

United States, Virginia

Norfolk, Virginia, United States

Belgium

Leuven, Vlaams-Brabant, Belgium

France

Saint-Etienne cedex 2, France

Hungary

Debrecen, Hajdu-Bihar Megye, Hungary

Italy

Varese, Italy

Netherlands

Amsterdam, Netherlands

Sponsors and Collaborators

Daiichi Sankyo, Inc.

Investigators

• Study Director: Global Clinical Leader; Daiichi Sankyo, Inc.

  Study Documents (Full-Text)

Documents provided by Daiichi Sankyo, Inc.:

Study Protocol and Statistical Analysis Plan  [PDF] January 20, 2016

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang TF, Yeo E, Zhang G, Zwicker JI, Weitz JI, Buller HR; Hokusai VTE Cancer Investigators. Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism. N Engl J Med. 2018 Feb 15;378(7):615-624. doi: 10.1056/NEJMoa1711948. Epub 2017 Dec 12.

van Es N, Di Nisio M, Bleker SM, Segers A, Mercuri MF, Schwocho L, Kakkar A, Weitz JI, Beyer-Westendorf J, Boda Z, Carrier M, Chlumsky J, Decousus H, Garcia D, Gibbs H, Kamphuisen PW, Monreal M, Ockelford P, Pabinger I, Verhamme P, Grosso MA, Buller HR, Raskob GE. Edoxaban for treatment of venous thromboembolism in patients with cancer. Rationale and design of the Hokusai VTE-cancer study. Thromb Haemost. 2015 Nov 25;114(6):1268-76. doi: 10.1160/TH15-06-0452. Epub 2015 Aug 13.

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT02073682
• Other Study ID Numbers: DU176b-D-U311; 2014-004708-30 ( EudraCT Number )
• First Posted: February 27, 2014
• Results First Posted: October 24, 2018
• Last Update Posted: March 6, 2019
• Last Verified: September 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• URL: https://vivli.org/ourmember/daiichi-sankyo/

Keywords provided by Daiichi Sankyo, Inc.:

Active Cancer with Metastasis

Additional relevant MeSH terms:

Pulmonary Embolism; Thrombosis; Embolism; Thromboembolism; Venous Thromboembolism; Venous Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Heparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin; Edoxaban; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors