Cancer Venous Thromboembolism (VTE)

NCT ID: NCT02073682

Last Updated: 2019-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1046 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-16
• Study Completion Date: 2017-09-15

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.

Conditions

Venous Thromboembolism (VTE); Deep Vein Thrombosis (DVT); Pulmonary Embolism (PE); Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Edoxaban group

After 5 days of low molecular weight heparin (LMWH), patients receive edoxaban treatment daily - tablet for oral use

Group Type: EXPERIMENTAL

Edoxaban

Intervention Type: DRUG

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.

Low molecular weight heparin

Intervention Type: DRUG

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.

Dalteparin group

Participants receive Dalteparin treatment daily -solution for subcutaneous injection

Group Type: ACTIVE_COMPARATOR

Dalteparin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

DU-176b; Active comparator; LMWH

Eligibility 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;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

Brandon, Florida, United States

Jonesboro, Georgia, United States

Detroit, Michigan, United States

Norfolk, Virginia, United States

Leuven, Vlaams-Brabant, Belgium

Saint-Etienne, , France

Debrecen, Hajdu-Bihar Megye, Hungary

Varese, , Italy

Amsterdam, , Netherlands

Countries

United States; Belgium; France; Hungary; Italy; Netherlands

References

Patell R, Hsu C, Shi M, Grosso MA, Duggal A, Buller HR, Raskob G, Zwicker JI. Impact of mild thrombocytopenia on bleeding and recurrent thrombosis in cancer. Haematologica. 2024 Jun 1;109(6):1849-1856. doi: 10.3324/haematol.2023.284192.

Reference Type: DERIVED

PMID: 37855029 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29231094 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26271200 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2014-004708-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DU176b-D-U311

Identifier Type: -

Identifier Source: org_study_id