Deep Vein ThrombosisPhase 3Resolve-DVTNCT04670432
Resolution Enhancement by a Supplemental Obstruction Lessening Venoactive Drug for Eight Weeks in Deep Vein Thrombosis
A Phase 3 study testing Hydroxyethylrutoside in people with Deep Vein Thrombosis, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Deep Vein Thrombosis
- What is being tested?
- Hydroxyethylrutoside
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteNetherlands
- Study dates
- 8 Dec 2020to 28 Nov 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Maastricht University Medical Center
Maastricht, Limburg, 6229 HX
About this study
Official title: Resolution Enhancement by a Supplemental Obstruction Lessening Venoactive Drug for Eight Weeks in Deep Vein Thrombosis: A Pilot Study to Evaluate if Hydroxyethylrutoside Reduces the Risk of Post-Thrombotic Syndrome in Patients With DVT.
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.
Read the 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
- Being tested
- Hydroxyethylrutoside
- Keywords
- Venoactive drugs, Hydroxyethylrutoside, Venoruton, Thrombus resolution, Residual Vein Obstruction, Post-Thrombotic Syndrome
- Medical subject headings
- Venous Thrombosis, Postthrombotic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydroxyethylrutosideDrug
Also called Venoruton
500 mg film-coated tablet
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | Experimental | Hydroxyethylrutoside oral tablet twice daily for 8 weeks starting at the time of randomization, in addition to usual care. Receives: Drug: Hydroxyethylrutoside |
| Control group | No intervention | Usual care, consisting of anticoagulant treatment and elastic compression therapy for full study duration. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Residual Vein Obstruction
Transversal vein diameter ≥2mm on duplex-ultrasound during full compression, which is assessed by a radiologist blinded for study allocation. A secondary assessment based on acquired images will be performed by an independent expert radiologist, again blinded for study allocation.
Measured: At 12 weeks
Secondary outcomes (6)
Levels of circulating biomarkers
A panel of biomarkers, associated with RVO and PTS, will be measured in venous blood at several time-points. These include markers of inflammation (e.g. IL6, IL10), cell adhesion (e.g. ICAM1, P-selectin), and remodelling (e.g. MMPs). Differences for each individual biomarker over time will be compared between groups.
Measured: At time of inclusion, 1 week, 4 weeks, 8 weeks and 12 weeks
Clinical sign severity
Objective Villalta score + circumference calf and ankle, which is measured by an assessor blinded to study allocation. Compared to the contralateral unaffected leg.
Measured: At time of inclusion, 1 week, 4 weeks, 8 weeks and 12 weeks
Symptom severity
Subjective Villalta score, which is answered directly by the patient through a survey
Measured: At time of inclusion, 4 weeks and 12 weeks
VEINS Quality of Life/Symptoms (VEINES-QOL/Sym)
This disease-specific quality of life score is answered directly by the patient through a survey.
Measured: At time of inclusion, 4 weeks and 12 weeks
Short Form 36 Health Survey (SF-36)
This general quality of life score is answered directly by the patient through a survey.
Measured: At time of inclusion, 4 weeks and 12 weeks
Euro Quality of Life 5D (EQ-5D)
This general quality of life score is answered directly by the patient through a survey.
Measured: At time of inclusion, 4 weeks and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2020
- Study start8 Dec 2020
- Primary completion28 Nov 2023
- Study completion28 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Deep Vein ThrombosisStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Netherlands Thrombosis Foundation
- Responsible party
- Sponsor
- Investigators
- Arina J ten Cate - Hoek, MD, PhD, Principal investigator, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04670432
- Sponsor's protocol ID
- NL73142.068.20
- Acronym
- Resolve-DVT
- Status last verified
- Feb 2024
- First submitted
- 20 Nov 2020
- Last updated
- 1 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 26462885
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Resolution Enhancement by a Supplemental Obstruction Lessening Venoactive Drug for Eight Weeks in Deep Vein Thrombosis: A Pilot Study to Evaluate if Hydroxyethylrutoside Reduces the Risk of Post-Thrombotic Syndrome in Patients With DVT.
- ClinicalTrials.gov ID
- NCT04670432
- Acronym / sponsor ID
- Resolve-DVT / NL73142.068.20
- Conditions
- Deep Vein Thrombosis
- Keywords
- Venoactive drugs, Hydroxyethylrutoside, Venoruton, Thrombus resolution, Residual Vein Obstruction, Post-Thrombotic Syndrome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- Netherlands Thrombosis Foundation
- Study start
- 8 Dec 2020 (actual)
- Primary completion
- 28 Nov 2023 (actual)
- Study completion
- 28 Nov 2023 (actual)
- First posted
- 17 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment group | Experimental | Drug: HydroxyethylrutosideHydroxyethylrutoside oral tablet twice daily for 8 weeks starting at the time of randomization, in addition to usual care. |
| Control group | No intervention | –Usual care, consisting of anticoagulant treatment and elastic compression therapy for full study duration. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydroxyethylrutosideAlso: Venoruton500 mg film-coated tablet | Drug | Treatment group |
Primary outcome
Residual Vein Obstruction
Time frame: At 12 weeks
Transversal vein diameter ≥2mm on duplex-ultrasound during full compression, which is assessed by a radiologist blinded for study allocation. A secondary assessment based on acquired images will be performed by an independent expert radiologist, again blinded for study allocation.
6 secondary outcomes
Levels of circulating biomarkers
Time frame: At time of inclusion, 1 week, 4 weeks, 8 weeks and 12 weeks
Clinical sign severity
Time frame: At time of inclusion, 1 week, 4 weeks, 8 weeks and 12 weeks
Symptom severity
Time frame: At time of inclusion, 4 weeks and 12 weeks
VEINS Quality of Life/Symptoms (VEINES-QOL/Sym)
Time frame: At time of inclusion, 4 weeks and 12 weeks
Short Form 36 Health Survey (SF-36)
Time frame: At time of inclusion, 4 weeks and 12 weeks
Euro Quality of Life 5D (EQ-5D)
Time frame: At time of inclusion, 4 weeks and 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2024.
- Background: PubMed 26462885ten 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arina J ten Cate - Hoek, MD, PhD principal investigator
Maastricht University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hydroxyethylrutoside in people with Deep Vein Thrombosis, run by Maastricht University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Residual Vein Obstruction (time frame: At 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04670432, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2024.