A Study of Dabigatran Etexilate as Primary Treatment of Malignancy Associated Venous Thromboembolism
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|ClinicalTrials.gov Identifier: NCT03240120|
Recruitment Status : Recruiting
First Posted : August 4, 2017
Last Update Posted : April 17, 2019
This trial aims at determining if dabigatran is effective in the treatment of malignancy associated VTE. Tolerance and safety of dabigatran will also be assessed.
This is a single armed trial of dabigatran in patients with malignancy associated VTE.
The target recruitment is 99 consecutive patients with active malignancy and newly diagnosed VTE (deep vein thrombosis and/or pulmonary embolism) in Queen Mary Hospital.
Tinzaparin 175 iu/kg daily will be started after the diagnosis of VTE is confirmed (duplex Doppler ultrasonography for deep vein thrombosis, and computed tomography for pulmonary embolism), and a written consent is obtained. Patients will be switched to dabigatran 150mg twice daily from day 6 onwards. The first dose of dabigatran will be given within 2 hours before the time that the next dose of tinzaparin would have been due. Anticoagulation will be continued as long as malignancy is active. If patients achieve a complete remission of their underlying malignancies, dabigatran will be continued for 6 months further.
|Condition or disease||Intervention/treatment||Phase|
|Venous Thromboembolism Deep Vein Thrombosis Pulmonary Embolism||Drug: Dabigatran etexilate Drug: Tinzaparin||Phase 3|
Patients with malignancies are at increased risks of venous thromboembolism (VTE). The annual incidence of VTE in cancer patients is 0.5%, which is 5-fold more than the general population . Low molecular weight heparin (LMWH) has been the standard treatment for malignancy-associated VTE. This recommendation follows the results of the Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent VenousThromboembolism in Patients with Cancer (CLOT) trial, which showed superiority of Low molecular weight heparin (LMWH) over warfarin in cancer patients with VTE .
Low molecular weight heparin (LMWH) has a number of inherent advantages over warfarin. It does not interact with chemotherapeutic agents, and dose titration is not necessary. Furthermore, the risks of both bleeding and breakthrough VTE are also lower with LMWH. However, the requirement of daily subcutaneous injection makes LWMH inconvenient to use. Most patients have difficulties continuing daily injection, partly owing to compliance issues, but also because an emaciated state in some patients makes subcutaneous injection painful. As the life expectancy of solid cancer patients is improved with novel treatment options, the choice of anticoagulation has become a major issue in the management of VTE in this patient population.
The main reason underlying the inferior performance of warfarin in oncology patients is difficult dose titration. Drug interaction and hepatic dysfunction are common in patients on chemotherapy. Frequent interruptions of warfarin for invasive procedures and chemotherapy-induced-thrombocytopenia also lead to fluctuations in anticoagulation level. As a result, highs risk of recurrence of VTE and bleeding were observed in cancer patients taking warfarin. Direct-acting oral anticoagulants (DOACs), on the other hand, may be an attractive alternative treatment to LMWH. They are administered at a fixed dose with predictable pharmacokinetics, so that therapeutic monitoring is not required. There is minimal food and drug interaction. They have been shown to be effective in the treatment of VTE in several pivotal randomized controlled trials in comparison with warfarin . However, their role in malignancy associated VTE is yet to be determined, because cancer patients were either excluded or very much underrepresented in these VTE treatment trials. Moreover, the non-inferiority of DOACs in VTE treatment was only demonstrated against warfarin, which is already shown to be suboptimal in oncology patients. A trial directly comparing DOACs with LMWH in malignancy associated VTE is therefore needed.
Dabigatran etexilate is an oral thrombin inhibitor. It was shown in the RECOVER study to be effective in treatment of VTE and it has a lower bleeding risk than warfarin. It is not metabolized by cytochrome P450 system and therefore, in contrast to other DOACs, concomitant administration of CYP3A4 inducers or inhibitors is not a concern.
We propose this prospective single armed trial to evaluate the efficacy and safety of dabigatran in the treatment of malignancy associated VTE. We will compare the result with our historical control who were treated with LMWH.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||99 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Prospective Study of Dabigatran Etexilate as Primary Treatment of Malignancy Associated Venous Thromboembolism|
|Actual Study Start Date :||September 1, 2017|
|Estimated Primary Completion Date :||May 31, 2021|
|Estimated Study Completion Date :||December 31, 2021|
Experimental: Dabigatran etexilate & Tinzaparin
Tinzaparin 175 iu/kg daily will be started after the diagnosis of VTE is confirmed dabigatran 150mg twice daily from Day 6 onward till 6 months after underlying disease remission.
Drug: Dabigatran etexilate
Pradaxa 150 mg hard capsules
Other Name: Pradaxa
Tinzaparin 175 iu/kg daily will be started after the diagnosis of VTE is confirmed
- Number of patients with symptomatic VTE [ Time Frame: up to 2 years ]first episode of objectively documented symptomatic recurrent VTE (deep vein thrombosis, pulmonary embolism)
- number of mortality, clinically relevant major and non-major bleeding [ Time Frame: up to 2 years ]bleeding (major and non-major) and death
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03240120
|Contact: Gloria Hwang, MBBS||852 22553111 ext email@example.com|
|Contact: Crosby Lu, MMedSc||852 22553111 ext firstname.lastname@example.org|
|The University of Hong Kong||Recruiting|
|Hong Kong, Hong Kong|
|Contact: Gloria Hwang, MBBS 852 22553111 ext 4826 email@example.com|
|Contact: Crosby Lu, MMedSc 852 22553111 ext 1654 firstname.lastname@example.org|
|Principal Investigator:||Gloria Hwang, MBBS||The University of Hong Kong|