Resolution Enhancement by a Supplemental Obstruction Lessening Venoactive Drug for Eight Weeks in Deep Vein Thrombosis

NCT ID: NCT04670432

Last Updated: 2024-03-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-08
• Study Completion Date: 2023-11-28

Brief Summary

The RESOLVE-DVT study is a randomized single-center pilot study to determine the effects of hydroxyethylrutoside (Venoruton) on aspects of deep vein thrombosis (DVT) resolution associated with post-thrombotic syndrome (PTS). Based on these results, the investigators will estimate its potential as a preventive therapy for PTS.

Eligible consenting patients who develop an acute, objectively confirmed DVT will be randomized and equally allocated to two trial arms, either the treatment group (Venoruton tablet 500 mg twice daily) or the control group (usual care). The pilot trial consists of 5 study contacts over 12 weeks at which outcome assessment is performed: inclusion, 1 week, 4 weeks, 8 weeks, 12 weeks. Treatment allocation is masked for outcome assessors, but not for patients.

Detailed Description

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.

Conditions

Deep Vein Thrombosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Treatment group

Hydroxyethylrutoside oral tablet twice daily for 8 weeks starting at the time of randomization, in addition to usual care.

Group Type: EXPERIMENTAL

Hydroxyethylrutoside

Intervention Type: DRUG

500 mg film-coated tablet

Control group

Usual care, consisting of anticoagulant treatment and elastic compression therapy for full study duration.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Hydroxyethylrutoside

500 mg film-coated tablet

Intervention Type: DRUG

Other Intervention Names

Venoruton

Eligibility Criteria

Inclusion Criteria

• Adult, defined as ≥ 18 years of age
• Objectively confirmed DVT by DUS
• Proximal DVT, defined as iliofemoropopliteal venous thrombosis
• Acute DVT, defined as having symptoms for ≤ 7 days at presentation
• Willing and able to give written informed consent

Exclusion Criteria

• Previous DVT
• Bilateral DVT
• Pre-existent chronic venous insufficiency (CEAP-criteria C ≥ 3)
• Active malignancy, inflammatory disease (e.g. rheumatoid arthritis), or immunosuppressive therapy
• Current pregnancy or breast feeding
• Indication for therapeutic thrombolysis
• Contra-indication for DOAC

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Netherlands Thrombosis Foundation

UNKNOWN

Sponsor Role: collaborator

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arina J ten Cate - Hoek, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Maastricht University Medical Center

Locations

Maastricht University Medical Center

Maastricht, Limburg, Netherlands

Countries

Netherlands

References

ten Cate-Hoek AJ, Henke PK, Wakefield TW. The post thrombotic syndrome: Ignore it and it will come back to bite you. Blood Rev. 2016 Mar;30(2):131-7. doi: 10.1016/j.blre.2015.09.002. Epub 2015 Oct 9.

Reference Type: BACKGROUND

PMID: 26462885 (View on PubMed)

Other Identifiers

NL73142.068.20

Identifier Type: -

Identifier Source: org_study_id