Health Condition 1: null- acute venous thromboembolism in patients with active cancer"
Conditions
Interventions
Intervention1: Innohep® (tinzaparin sodium) 20,000 anti-Xa IU/ml,: Dosing Innohep®: 175 anti-Xa IU/kg body weight once daily by SC injection.
Control Intervention1: Warfarin: tablets of 1 mg, 3 mg,
Sponsors
LEO Pharma AS
Eligibility
Inclusion criteria
Inclusion criteria: 1.Patients with a diagnosis of active cancer with a histologically or cytologically diagnosed solid tumour or haematological malignancy (evidence of early stage, regional or metastatic disease). Active cancer is defined as: Patients diagnosed with cancer within the past 6 months, OR Patients with recurrent, advanced or metastatic disease, OR Patients that have received any treatment for cancer during the previous 6 months, OR Patients not in complete remission of a chronic haematological malignancy. 2.Symptomatic and objectively confirmed acute proximal lower-limb deep vein thrombosis (DVT) (anatomically including popliteal, femoral [superficial and common] and iliac [external and common]) and/or pulmonary embolism (PE) (located in segmental or larger pulmonary arteries) diagnosed within 72 hours prior to randomisation. Diagnosis of DVT/PE (at randomisation and at recurrence) must be made by appropriate objective imaging. 3. 18 years of age or above the legal age of consent as per country specific regulations. 4.Patients with Eastern Co-operative Oncology Group (ECOG) performance status of 0, 1 or 2 prior to the VTE episode. 5.Signed informed consent.
Exclusion criteria
Exclusion criteria: 1.Life expectancy < 6 months. 2.Patients with basal cell carcinoma or non-melanoma skin cancer. 3.Creatinine clearance; 20 ml/min according to the abbreviated Modification of Diet in Renal Disease (aMDRD) formula. 4.Contra-indications to anticoagulation: a.Active or recent (< 1 month) clinically significant bleeding, including gastrointestinal bleeding or peptic ulcer. b.History of bleeding disorder or coagulopathy (congenital, acquired or unexplained repeated bleeding episodes). c.Uncontrolled arterial hypertension (systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg). d.Recent intracranial haemorrhage (in the last 1 month prior to randomisation) which is at high risk of rebleeding and would prohibit anticoagulant therapy, according to the Investigator's judgment. e.Recent (in the last 1 month prior to randomisa-tion) brain, spinal or ophthalmic surgery. f.Thrombocytopenia (platelet count < 50 x 109/ L). g.Coagulopathy due to liver insufficiency as indicated by a prolonged baseline activated partial thromboplastin time (aPTT) > 1.5 x upper limit of normal (ULN) or equivalent to an aPTT ratio > 1.5 (if not receiving low molecular weight heparin [LMWH] /unfractionated heparin [UFH]) 5.Known hypersensitivity to the investigational product (Innohep®) or the reference product (warfarin). 6.History of heparin-induced thrombocytopenia (HIT). 7.Pre-randomisation therapeutic anticoagulant treatment for acute VTE administered for more than 72 hours prior to randomisation. 8.Patients that had been receiving therapeutic anticoagulation at the time of the VTE event (i.e. anticoagulant failure), using any anticoagulant, such as: a.Parenteral anticoagulants e.g. UFH, LMWH, fondaparinux, bivalirudin or hirudin. b.Vitamin K antagonists (VKA). c.New oral anticoagulants, e.g. dabigatran, rivaroxaban. Note: Chronic treatment with anti-platelet agents such as low dose of aspirin (up to 325 mg/day), clopidogrel or ticlopidine is allowed). 9.Patients unlikely to comply with the protocol, e.g. inability to return for study visits or inability to receive/administer daily subcutaneous (SC) injection. 10.Participation in another interventional study with active drug treatment or an investigational device. 11.Pregnant or breast-feeding women. Pregnancy status should be checked by serum or urine pregnancy testing prior to inclusion. 12.Women of childbearing potential not protected by an effective contraceptive method (as defined for contra-ception in the Informed Consent Form [ICF]) for the duration of the study. 13.Sexually active fertile men if they, or their partner (being a woman of childbearing potential), is not using effective birth control.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of the study is to assess the efficacy of Innohep® in preventing the recurrence of VTE in patients with active cancer who have had an acute VTE episode.Timepoint: Each scheduled visit (Visit 1 and onwards) and telephone-contacts will include a standardised assessment (standardized questionnaire) of the signs and symptoms of recurrent VTE | — |
Secondary
| Measure | Time frame |
|---|---|
| Assess health-related quality of life (QoL).Timepoint: Health related QoL will be assessed using the EQ-5D at baseline, each monthly visit and the Post-Treatment Follow-Up Visit ;Assess healthcare resource utilisationTimepoint: Healthcare resource utilisation data will be collected for assessments at each monthly visit and the Post-Treatment Follow-Up Visit; major healthcare resources associated with the prevention of recurrent VTE and the management of VTE, HIT and bleeding events will be recorded;Assess incidence and severity of post-thrombotic syndrome (PTS).Timepoint: PTS will be assessed at baseline, at each monthly visit and at the end of the 1-Month Post-Treatment Follow-Up Period, using the Villalta scale that allows the staging of PTS severity using clinical measures.;Assess overall mortality at 6 monthsTimepoint: Health related QoL will be assessed using the EQ-5D at baseline, each monthly visit and the Post-Treatment Follow-Up Visit. Healthcare resource utilisation data will be collected for assessments at each monthly visit and the Post-Treatment Follow-Up Visit; major healthcare resources associated with the prevention of recurrent VTE and the management of VTE, HIT and bleeding events will be recorded. ;Assess the safety of long-term Innohep®.Timepoint: Safety will be assessed via the monitoring of bleeding events, HIT events and deaths, other objectively confirmed thromboses, clinically significant abnormal laboratory data, clinically significant vital signs and all other AEs.;identify clinical risk factors for recurrent VTE and major bleeding.Timepoint: Coagulation biomarkers (e.g. D-dimer and tissue factor) will be assessed at the baseline and End of Treatment visits VTE Risk factors (e.g. tumour type, body mass index [BMI], platelets, haemoglobin, and leucocytes) will be assessed at baseline and at the time of a VTE event;Identify the possible role of coagulation parameters to predict recurrent VTE or prognosis.Timepoint: Coagulation biomarker | — |
Countries
Thailand
Contacts
Public ContactMr Sunil Garg
INC Research
Outcome results
None listed