Rationale: After a DVT, one in three patients develops PTS of the affected leg, despite
anticoagulant treatment and 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 would be of high value. Since the
pathogenesis of PTS is mediated through persistent inflammation during thrombus resolution,
causing damage to the vein wall resulting in venous insufficiency, the venoactive flavonoids
with their vasoprotective and anti-inflammatory properties provide an excellent candidate. As
investigational medicinal product, the highly effective flavonoid 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 study.
Study population: Adults presenting themselves at the emergency department (ED) with a first,
acute, proximal DVT of the lower extremity. Inclusion will be performed within 48 hours after
diagnosis of DVT.
Intervention: Administration of 500 mg Venoruton twice daily for 8 weeks following DVT, in
addition to standard treatment by ECT and anticoagulant therapy.
Baseline characteristics: Assessments include demographic data, smoking status, site and
extension of DVT, side of affected leg, duration of complaints at time of diagnosis, risk
factors for DVT (immobilisation, trauma, etc.), type of ECT, presence/suspicion of pulmonary
embolism, concomitant medications.
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.
Additional study parameters: Medication adherence and ECT compliance at 1 week, 4 weeks, 8
weeks and 12 weeks. Pill count of Venoruton at 8 weeks. Pill count of direct oral
anticoagulant (DOAC) at 12 weeks. The occurrence of relevant (serious) adverse events is
assessed at all visits.
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. The first visit coincides with inclusion and
two subsequent 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.