Lead Investigator: Saskia Middeldorp, Amsterdam UMC
Title of Proposal Research: Hokusai post VTE study: long-term outcome after heparin plus edoxaban versus heparin plus vitamin K antagonists for acute deep vein thrombosis and pulmonary embolism
Vivli Data Request: 5904
Funding Source: None
Potential Conflicts of Interest: The current data request is done for the analyses of two IITs that are being done in close collaboration with DS. For these, prof Middeldorp has received grants from Daiichi Sankyo for investigator-initiated studies into the long term outcome of venous thrombosis and pulmonary embolism in patients treated with edoxaban or warfarin (contracts signed March 2016). Daiichi Sankyo is not involved in the analysis or publication of results, but will be notified prior to submission of publication.
Summary of the Proposed Research:
1. General background on venous thrombosis
Thrombosis is a blood clot in a vein or artery, for example in the leg (deep vein thrombosis (DVT)), or the lungs (pulmonary embolism (PE)). Venous thrombosis is the third most common cardiovascular disease with an annual incidence of 1 per 1000 adults. Acute thrombosis should be promptly treated with anticoagulants. Despite adequate treatment, sequelae can occur: post thrombotic syndrome (PTS) and post-pulmonary embolism (post-PE) syndrome are long-term complications of DVT and PE, respectively. Both complications usually become apparent within 2 years after the acute blood clot. However, it is still not fully understood how these long-term complications develop.
2. Post thrombotic syndrome
After acute DVT, complaints of the leg persist in 20-50% of the patients. Persisting symptoms are called PTS and may vary from minor symptoms including skin discoloration, small dilated blood vessels around the ankle, discomfort and mild swelling, to severe symptoms such as chronic pain, severe swelling or even leg wounds. Therapeutic and preventive options to cure PTS are limited. The use of elastic compression stockings is the only intervention, which can possibly prevent PTS after a DVT and which can partly diminish symptoms in patients who suffer from PTS. Due to its high prevalence, severity and chronicity, PTS has a significant impact on quality of life (QoL) and is associated with considerable socioeconomic consequences for both the patient and the health care system.
3. Post-PE syndrome
After an acute episode of PE, half of patients report persistent shortness of breath – and functional limitations. This is called post-PE syndrome. In most cases symptoms are a result of deterioration of physical condition, persistent small thrombosis or other diseases linked to the lungs or the heart. In the most severe cases (0.5-4%), the post-PE syndrome is a result of a hypertensive disease in the pulmonary arteries, as a result of incomplete clot resolution. The shortness of breath that characterizes the post-PE syndrome may lead to decreased QoL.
4. Description HOKUSAI VTE trial
In the Hokusai VTE trial (2010-2012), two types of anticoagulants were assessed for the treatment of acute thrombosis: standard treatment with heparin followed by vitamin K antagonists (VKA) and the novel direct oral anticoagulant (DOAC) edoxaban. The study was conducted in patients presenting with an acute DVT and in patients who presented with an acute PE (with or without DVT).
5. Current follow up study (HOKUSAI post VTE trial) comprising of Hokusai post DVT and Hokusai post-PE studies
a. HOKUSAI post DVT study
In the current follow-up study (2017-2020), patients who previously participated in the Hokusai DVT trial were invited to participate. Patients with a DVT were invited for a leg assessment (to diagnose post-thrombotic syndrome) during a single hospital visit and were asked to complete questionnaires on QoL.
b. HOKUSAI post PE study
In the current follow-up study (2017-2020), patients who previously participated in the Hokusai PE trial were invited to participate. Patients with a PE were interviewed by telephone and were asked to fill the questionnaires on QoL.
6. Combining HOKUSAI VTE trial results with HOKUSAI post VTE trial data + hypothesis
The investigators will combine the collected data from their follow-up study with data from the original Hokusai VTE trial in order to report the results per allocated treatment arm and to be able to correct for baseline characteristics at time of index event.
Since DOACs have a more stable pharmacologic profile than VKA, we hypothesize that treatment of DVT and PE with the DOAC edoxaban leads to improved thrombus resolution and thereby less long-term sequelae, translating into better Quality of Life and a lower incidence of PTS in patients who presented with a DVT, compared to treatment with VKA.
A Phase 3, Randomized, Parallel-Group, Multi-Center, Multi-National Study for the Evaluation of Efficacy and Safety of (LMW) Heparin/Edoxaban Versus (LMW) Heparin/Warfarin in Subjects With Symptomatic Deep-Vein Thrombosis (DVT) and or Pulmonary Embolism (PE)
Sponsor: Daiichi Sankyo, Inc.
Study ID: NCT00986154
Sponsor ID: DU176b-D-U305
Update: This data request was withdrawn on 24 November 2020 by the researcher.