RecruitingPhase 2ACTRN12617000331336

Anticoagulant therapy for cancer-associated blood clots

A Phase 2 study of safety of Rivaroxaban compared with Low Molecular Weight Heparin (LMWH) for acute therapy of cancer-associated venous thromboembolism

Sponsor

South East Sydney and Illawarra Area Health Service

Enrollment

600 participants

Start Date

Apr 4, 2017

Study Type

Interventional

Conditions

Venous Thromboembolism Pulmonary Embolism Deep Vein Thrombosis

Summary

The primary purpose of this trial is to evaluate the safety of rivaroxaban for the treatment of thrombosis associated with cancer, in comparison to the standard care treatment with low molecular weight heparin (LMWH). Who is it for? You may be eligible to enroll in this trial if you are aged 18 or over and have active cancer and require therapeutic anticoagulation for a new diagnosis of deep vein thrombosis or pulmonary embolism. The duration of anticoagulant treatment should be for at least 6 months. Study details All participants enrolled in this trial will be randomly allocated (by chance) to receive either treatment with rivaroxaban or treatment as per standard care with LMWH for at least 6 months. Patients can either be enrolled within 72 hours of diagnosis, or at day 30 +/- 2 days. Participants will be assessed six months later for side effects of treatment, including any bleeding which has occurred. It is hoped that the findings from this trial will provide information on whether rivaroxaban is a safe alternative to LMWH for the treatment of cancer-associated thrombosis.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria5

Active malignancy defined by diagnosis of cancer (excluding non-melanomatous skin malignancy), recurrent cancer, or treatment for cancer within last 12 months.
Acute symptomatic and objectively proven VTE, either proximal DVT or PE, requiring therapeutic anticoagulation for at least 3 months.
Aged 18 years or older at time of inclusion
Patient eligible for PBS subsidised LMWH and rivaroxaban (supplied by authority prescriptions).
Able to attend outpatient clinic for follow-up assessment.

Exclusion Criteria11

Patient received >72 hours (Cohort R1) or >32 days (Cohort R2) weeks of therapeutic anticoagulation.
Cessation of therapeutic anticoagulation for > 24 hours once commenced.
Severe renal impairment defined by calculated GFR (Cockcroft-Gault) <30 mLs/minute. Significant hepatic disease (including moderate to severe hepatic impairment, i.e. Child-Pugh B and C) or ALT > 3 x ULN.
Concomitantly treated with strong inhibitors of both CYP 3A4 and P-glycoprotein such as HIV protease inhibitors (e.g. ritonavir) or systemically administered azole anti-mycotics (ketoconazole, itraconazole, posaconazole, voriconazole)
Clinically significant active bleeding such that full therapeutic anticoagulation is contraindicated
Serious haemorrhage within last 4 weeks requiring hospitalisation, transfusion or surgical intervention.
Investigator deem patient at high risk of bleeding on anticoagulation. Reasons may include (but not be restricted to) uncontrolled hypertension, recent surgery to brain spine or eye, recent gastro-duodenal ulceration, presence of coagulopathy (INR >1.5 or platelet count <60 x 10^9/l), significant familial bleeding tendency, absolute necessity for dual anti-platelet therapy.
Indication for long term anticoagulation (e.g. mechanical heart valve, prior stroke in context of AF)
Pregnant or of childbearing potential and not using adequate contraception
Expected life span <6 months and/or ECOG 4 at enrolment.
Geographically inaccessible for follow-up.

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Interventions

Study intervention will be commenced immediately after randomisation and within 72 hours (cohort R1) or between 30 +/- 2 days (cohort R2) after commencement of therapeutic anticoagulation according to initial consent and election for treatment. Standard of care anticoagulant therapy is low molecular weight heparin of choice injected subcutaneously (protocol recommends dalteparin 200 IU /kg once daily as per Product Information) . The study intervention will be Rivaroxaban 15mg twice daily per oral for 3 weeks and then 20mg once daily thereafter. Rivaroxaban: oral tablet Duration of administration: 6 months monitor adherence: clinic review Cohort R1 refers to patients who are randomised to oral rivaroxaban or standard of care within 72 hours of diagnosis of venous thromboembolism. Cohort R2 refers the patients who are randomised to oral tablet rivaroxaban or standard of care at timepoint 30 days +/- 2 days of diagnosis of venous thromboembolism..