Venous Thromboembolism (VTE)Phase 3NCT02073682
Cancer Venous Thromboembolism (VTE)
A Phase 3 study testing Edoxaban, Dalteparin and Low molecular weight heparin in people with Venous Thromboembolism (VTE) and Deep Vein Thrombosis (DVT), run by Daiichi Sankyo at 9 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Venous Thromboembolism (VTE), Deep Vein Thrombosis (DVT), Pulmonary Embolism (PE)
- What is being tested?
- Edoxaban, Dalteparin and Low molecular weight heparin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,046 participants
- Where
- 9 sitesin 6 countries
- Study dates
- 16 Jul 2015to 15 Sep 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Trial locations and contacts
9 sites in 6 countries.
9 sites in 6 countries
United States4 sites
Study site
Brandon, Florida
Study site
Detroit, Michigan
Study site
Jonesboro, Georgia
Study site
Norfolk, Virginia
About this study
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
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.
- Being tested
- Edoxaban, Dalteparin, Low molecular weight heparin
- Keywords
- Active Cancer with Metastasis
- Medical subject headings
- Venous Thromboembolism, Venous Thrombosis, Pulmonary Embolism, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EdoxabanDrug
Also called DU-176b
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.
DalteparinDrug
Also called Active comparator
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.
Low molecular weight heparinDrug
Also called LMWH
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.
| Study group | Role | What they receive |
|---|---|---|
| Edoxaban group | Experimental | After 5 days of low molecular weight heparin (LMWH), patients receive edoxaban treatment daily - tablet for oral use Receives: Drug: Edoxaban; Drug: Low molecular weight heparin |
| Dalteparin group | Active comparator | Participants receive Dalteparin treatment daily -solution for subcutaneous injection Receives: Drug: Dalteparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adjudicated Recurrent Venous Thromboembolism (VTE) or Major Bleeding Event
Measured: 12 months
Secondary outcomes (6)
Number of Participants With Adjudicated Major Bleeding Events While on Treatment
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).
Measured: 12 months
Number of Participants With Recurrent Venous Thromboembolism (VTE) During the Overall Study Period
Measured: 12 months
Number of Participants With Recurrent Deep Vein Thrombosis (DVT) During the Overall Study Period
Measured: 12 months
Number of Participants With Recurrent Non-Fatal Pulmonary Embolism (PE) During the Overall Study Period
Measured: 12 months
Number of Participants With VTE-Related Death
Measured: 12 months
Number of Participants With Recurrent VTE, Major Bleed or All-Cause Death
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2014 (estimated)
- Study start16 Jul 2015
- Primary completion15 Sep 2017
- Study completion15 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Venous Thromboembolism (VTE)Studies of the same condition, open and under way.
- More trials run by Daiichi SankyoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,046 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Global Clinical Leader, Study director, Daiichi Sankyo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02073682
- Sponsor's protocol ID
- DU176b-D-U311
- Other IDs
- 2014-004708-30, 2014
- Status last verified
- Sep 2018
- First submitted
- 25 Feb 2014
- Last updated
- 6 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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/
Publications
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.
PubMed 37855029Raskob 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.
PubMed 29231094van 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.
PubMed 26271200
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02073682
- Acronym / sponsor ID
- DU176b-D-U311
- Keywords
- Active Cancer with Metastasis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,046 participants (actual)
- Lead sponsor
- Daiichi SankyoIndustry (pharma, biotech, devices)
- Study start
- 16 Jul 2015 (actual)
- Primary completion
- 15 Sep 2017 (actual)
- Study completion
- 15 Sep 2017 (actual)
- First posted
- 27 Feb 2014 (estimated)
- Results
- Posted 24 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Edoxaban group | Experimental | Drug: Edoxaban, Drug: Low molecular weight heparinAfter 5 days of low molecular weight heparin (LMWH), patients receive edoxaban treatment daily - tablet for oral use |
| Dalteparin group | Active comparator | Drug: DalteparinParticipants receive Dalteparin treatment daily -solution for subcutaneous injection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EdoxabanAlso: DU-176bAfter 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. | Drug | Edoxaban group |
| DalteparinAlso: Active comparatorDalteparin 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. | Drug | Dalteparin group |
| Low molecular weight heparinAlso: LMWHTherapeutic 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. | Drug | Edoxaban group |
Primary outcome
Number of Participants With Adjudicated Recurrent Venous Thromboembolism (VTE) or Major Bleeding Event
Time frame: 12 months
6 secondary outcomes
Number of Participants With Adjudicated Major Bleeding Events While on Treatment
Time frame: 12 months
Number of Participants With Recurrent Venous Thromboembolism (VTE) During the Overall Study Period
Time frame: 12 months
Number of Participants With Recurrent Deep Vein Thrombosis (DVT) During the Overall Study Period
Time frame: 12 months
Number of Participants With Recurrent Non-Fatal Pulmonary Embolism (PE) During the Overall Study Period
Time frame: 12 months
Number of Participants With VTE-Related Death
Time frame: 12 months
Number of Participants With Recurrent VTE, Major Bleed or All-Cause Death
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37855029Patell 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.
- Derived from this study: PubMed 29231094Raskob 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.
- Derived from this study: PubMed 26271200van 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.
- Individual participant dataSharing planned: Yes. 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/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Global Clinical Leader study director
Daiichi Sankyo
9 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Edoxaban, Dalteparin and Low molecular weight heparin in people with Venous Thromboembolism (VTE) and Deep Vein Thrombosis (DVT), run by Daiichi Sankyo at 9 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Belgium, France, Hungary, Italy and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adjudicated Recurrent Venous Thromboembolism (VTE) or Major Bleeding Event (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02073682, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2019; AzTrials last refreshed its copy on 2 Nov 2026.