WAVe Study - Weight Adjusted Dalteparin for Patients Over 90 kg With Acute Cancer Associated Venous Thromboembolism

Titre officiel

A Multicentre Prospective Cohort Study Assessing the Use of Weight-Adjusted Low-Molecular-Weight-Heparin in Patients Over 90 kg With Acute Cancer-Associated Venous Thromboembolism

Sommaire:

Des patients atteints de cancer présentant des caillots de sang sont traités par des injections d’héparine de faible poids moléculaire (HFPM). La dose de l’une de ces HFPM, la daltéparine, est déterminée d’après le poids des patients à l’aide de la formule de 200 unités internationales (UI) par kg. La posologie actuelle de daltéparine approuvée par Santé Canada comprend une dose quotidienne maximale de 18 000 UI/jour, ajustée en fonction du poids pour les patients allant jusqu’à 90 kg. Tout patient de plus de 90 kg prend la même dose, quel que soit son poids. L’objectif de cette étude est d’évaluer l’innocuité de la dalteparine ajustée en fonction du poids chez des patients atteints de thromboembolie veineuse associée au cancer pesant plus de 90 kg.

Description de l'essai

Primary Outcome:

• Major bleeding episode

Secondary Outcome:

• Clinically relevant non major bleeding events
• Minor bleeding events
• Recurrent VTE events
• Overall mortality
• Bioaccumulation of study drug

The study is designed as a multicentre prospective cohort study with multiple Canadian sites. It will be initiated at The Ottawa Hospital prior to being offered externally. After obtaining informed consent, and confirming eligibility, participants weighing more than 90 kg with acute cancer-associated thrombosis will be treated with therapeutic weight-adjusted dalteparin (subcutaneous once daily injection, or twice daily, if the conditions of the participant do not allow once daily injection as per clinical judgement) beginning at enrolment (within 12 hours) and continuing until Day 30 visit. Subjects will receive therapeutic doses of dalteparin at a dose of approximately 200 IU/kg SC daily (up to 33,000 IU) for one month. Following this study period of 30 days (± 4 days), patients will be followed for 5 months. During the follow-up period, each patient will pursue his/her treatment as per usual standard treatment protocols provided at each institution. Treatment used and clinical outcomes will be collected at the end of the follow-up period. The majority of Canadian Thrombosis specialists use weight adjusted dosing of dalteparin in patients weighing more than 90 kg with cancer-associated VTE. No expert recommends capping the dose of dalteparin to 18,000 IU in patients weighing over 90 kg as suggested by the product monograph. However, the risk of major bleeding episodes in patients over 90 kg receiving weight-adjusted LMWH remains unclear. The estimated rate of major bleeding episodes of patients with cancer associated VTE (Mean weight 79.1 kg) managed with therapeutic dose of dalteparin is 3.6% (95% CI: 1.9 to 6.2). We hypothesize that the rate of major bleeding events will be similar in patients (> 90 kg) with cancer-associated VTE treated with dalteparin 200 IU/kg daily (up to 33,000 IU). We plan to recruit 150 patients in this cohort study. We expect 6 major bleeding events. This would provide us with an overall bleeding event of 4% with an upper bound of the confidence interval of 8.5%). An informal survey of Canadian thrombosis expert has demonstrated that clinicians would feel reassured and continue to use weight-adjusted dalteparin in cancer patients weighing more than 90kg if the upper bound of the 95% confidence interval is less than 9% (i.e. < 3% possible absolute rate difference).

Voir cet essai sur ClinicalTrials.gov