Improved blood clot resolution by a drug for eight weeks

Rationale: One in three patients experiences chronic signs and symptoms in the affected leg after deep vein thrombosis (DVT). This is referred to as the post-thrombotic syndrome (PTS). Current prevention of PTS is limited to elastic compression therapy (ECT) in the acute phase of DVT. Considering the major societal burden associated with PTS, supplementation of current prevention with an effective pharmacotherapeutic therapy could be of high value. Since the pathogenesis of PTS is mediated through inadequate thrombus resolution causing damage to vessel walls and increasing inflammation, the venoactive flavonoids with their vasoprotective and anti-inflammatory properties provide an excellent candidate. As investigational medicinal product, the highly effective flavonoid O-β-hydroxyethylrutoside (Venoruton) was chosen. Objective: To assess the effect of Venoruton on PTS-associated aspects of DVT resolution. Study design: A single-center, randomized, controlled, pilot trial. Study population: Adults presenting themselves at the emergency department (ED) with a first, acute, proximal DVT of the lower extremity. Intervention: Administration of 500 mg Venoruton twice daily for 8 weeks following DVT, in addition to standard treatment by ECT and anticoagulant therapy. Main study parameters: The primary study outcome is residual vein obstruction (RVO), assessed by duplex ultrasound (DUS) at 12 weeks after DVT. Main secondary outcomes are levels of circulating biomarkers and severity of PTS-characterizing clinical signs at baseline, 1 week, 4 weeks, 8 weeks and 12 weeks. Moreover, we measure quality of life (QoL) and PTS-characterizing symptoms at baseline, 4 weeks and 12 weeks. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients have a follow-up duration of 12 weeks after diagnosis of DVT. In addition to their visit at the ED, patients will visit the outpatient clinic four times during follow-up. At each visit secondary outcomes are measured through questionnaires, blood withdrawal and assessment of the affected leg. Two visits (4 and 12 weeks) coincide with the regular clinical care pathway. The primary outcome, RVO, is measured at 12 weeks after DVT by DUS. Patients allocated to the intervention group will take two oral tablets daily over a period of eight weeks. Venoruton has been established as safe with rarely occurring, mild, reversible side-effects through many years of experience. Masking: while patients are aware of their treatment allocation, the physicians and researchers are not, as to provide unbiased outcome assessment.

Treatment with Venoruton prevents RVO, which is a surrogate outcome of PTS.

Biomarkers and clinical signs at baseline, 1 week, 4 weeks, 8 weeks and 12 weeks; Symptoms and QoL at baseline, 4 weeks and 12 weeks; RVO at 12 weeks; Medication adherence and ECT compliance at 1 week, 4 weeks, 8 weeks and 12 weeks; Pill count Venoruton at 8 weeks; Pill count DOAC at 12 weeks.

Treatment with Venoruton 500mg film-coated tablets oral twice daily for eight weeks after DVT