Chronic Venous InsufficiencyPhase 4NCT01848210

Efficacy and Safety of Coumarin and Troxerutin in the Symptomatic Treatment of Chronic Venous Insufficiency

A Phase 4 study testing Coumarin/troxerutin in people with Chronic Venous Insufficiency, run by Takeda.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The purpose of this study is to evaluate the efficacy and safety of the fixed-dose combination of coumarin and troxerutin versus placebo in the symptomatic treatment of chronic venous insufficiency. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Chronic Venous Insufficiency
What is being tested?: Coumarin/troxerutin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 829 participants
Where: No sites listed yet
Study dates: May 2013to Sep 2015
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Consent of subject or legal representative
Men or women of any ethnicity, aged between 18 and 75 years, and body mass index (BMI) equal or less than 40.
Is able to use properly the medication according to protocol.
Has chronic venous insufficiency in the reference leg with the clinical classification C3, or C4a orC4b or C5, provided that in two last situations the present lipodermatosclerosis does not compromise more than 1/3 portion of the leg immersed or immersible in the plethysmometer.
Has stable edema (in a steady state), equivalent to a variation lower than or equal to 10% in partial volume of the reference leg between the screening visit and the randomization visit, and present for at least 6 months.
Scoring in "Severity Score of Local Complaints" equal to or higher than 5 total points.
Women who are using an effective (at the discretion of the investigator), but not hormonal, birth control method (not hormonal intrauterine device (IUD), surgical sterilization, among others), or who are postmenopausal, in addition to condom use (mandatory).

Who cannot join

Has chronic venous insufficiency classified as C1, C2 in the reference leg or C6 in any leg.
Has chronic venous insufficiency C4b or C5 in the reference leg, with lipodermatosclerosis present in more than 1/3 portion of the leg immersed in the plethysmometer.
Has unstable edema, equivalent to variation of more than 10% of partial volume in the reference leg between the screening visit and randomization visit, prior to start of treatment.
Has venous obstruction and/or deep vein thrombosis (DVT) and/or presence of phlebitis in lower limbs during the last 3 (three) months.
Has developed deep vein insufficiency during the last 3 (three) months.
Has other diseases that may interfere in the findings of the study such as: lymphedema, thrombosis, clotting disorders, edema of lower limbs due to right-sided heart failure, arterial obstruction of lower limbs and other conditions that, at medical discretion, are relevant to exclusion, particularly symptoms which are similar to the symptomatology of chronic venous insufficiency.

Show all 24Show fewer

Has a history of surgery at the venous system or sclerotherapy or who received any treatment for chronic venous insufficiency during the last 03 months, whether it was by drug, elastic stocking, laser, or surgery.
Has used previously Venalot® and had no benefits with the treatment.
Has a previous history of known or suspected allergy or intolerance to any of the ingredients of the medicinal product under investigation.
Has any clinical finding (history and physical examination) that is interpreted by the physician-investigator as a risk to participant's participation in the study.
Has known serious systemic disease, according to the medical and/or laboratory history.
Has history of a known liver disease such as hepatitis A, hepatitis B, or C.
Has changed at least one lab parameters: aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (gamma-GT), or alkaline phosphatase 2.5 times above the upper limit of normal range; hemoglobin less than 10 g/dL; clearance of creatinine estimative equal or above 60mL/min/1.73 m^2; platelets below 90,000/mL; and total bilirubin and fractions 1.5 times above the normal values.
Has been using diuretics for a period less than or equal to 6 months due to any disease (hypertension, renal failure, or other).
Has serious chronic liver or kidney disease, according to the medical and/or laboratory history.
Has uncontrolled blood hypertension (systolic blood pressure > 180 mmHg or diastolic blood pressure > 100 mmHg) at randomization or clinical hypertensive urgency.
Has a previous history of diabetes mellitus on use of insulin.
Has received treatment with immunosuppressive drugs, including systemic corticosteroids within 30 days before the start of study (randomization visit), or who are receiving immunosuppressive treatments, or who have known congenital or acquired immunodeficiency.
Has malignant neoplasms, from any etiology, or who are receiving any type of anticancer treatment, unless when properly treated and with no evidence of recurrence during the last five years. Non-melanoma skin cancer is not an exclusion criterion.
Is unable to understand the guidelines specified in this protocol or who cannot attend all the study visits.
Has a previous history of alcoholism, drug abuse, psychological or emotional problems in the last 5 years that can invalidate the Informed Consent Form or restrain participant's ability to comply with the requirements of the protocol.
Pregnant or breastfeeding women, or those who have the potential to become pregnant and are not using an appropriate contraceptive method.
Women who are using hormonal contraceptives or hormone replacement treatment, including phytoestrogens, within the last 3 months.
Took part in clinical trials during the last year.

About this study

Official title: Evaluation of Efficacy and Safety of the Fixed-dose Combination of Coumarin and Troxerutin (Venalot®) Versus Placebo in the Symptomatic Treatment of Chronic Venous Insufficiency - VENACT

The purpose of this study is to evaluate the efficacy and safety of the fixed-dose combination of coumarin and troxerutin versus placebo in the symptomatic treatment of chronic venous insufficiency.

Read the detailed description

The drug being tested in this study is the fixed-dose combination of coumarin and troxerutin called Venalot®. Venalot is being tested to treat the symptoms of chronic venous insufficiency. This study will look at symptom relief in people who take Venalot®.

The study will enroll approximately 808 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

Combination coumarin + troxerutin extended release tablets
Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient.

All participants will be asked to take two tablets three times a day throughout the study.

This multi-centre trial will be conducted in Brazil. The overall time to participate in this study is up to 18 weeks. Participants will make 6 visits to the clinic.

Conditions: Chronic Venous Insufficiency
Being tested: Coumarin/troxerutin, Placebo
Keywords: Drug therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Coumarin/troxerutinDrug
Also called Venalot®
Coumarin + troxerutin fixed-dose combination tablets
PlaceboDrug
Coumarin + troxerutin placebo-matching tablets

Study groups in NCT01848210
Study group	Role	What they receive
Coumarin 30 mg + Troxerutin 180 mg	Experimental	Coumarin 30 mg, troxerutin 180 mg fixed-dose combination tablets, orally, three times daily for up to 16 weeks. Receives: Drug: Coumarin/troxerutin
Placebo	Placebo comparator	Coumarin + troxerutin placebo-matching tablets, orally, three times daily for up to 16 weeks. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean Change (Reduction) From Baseline in Volume of Reference Leg at Week 16
Change in the partial volume of legs will be measured using a water plethysmometer. The volume of water (at 34 ± 0.2 °C) displaced after limb immersion is collected in an empty plastic Beaker which has been previously weighed (scale tare). The equilibrium/stability will be estimated using the absolute difference between measures of volume obtained at the Week 16 visit and Baseline to determine the reduction in edema.
Measured: Baseline and Week 16

Secondary outcomes (3)

Change (Reduction) From Baseline in Local Complaint Severity
Local Complaint Severity will be assessed using the Severity Score of Local Complaints that comprises 8 items: 1=tired legs, 2=heavy legs, 3= feeling of tension, 4=feeling of swelling, 5=aching legs, 6=tingling, 7=itching, 8=burning of soles of the feet.
Each item is classified with a Likert-type scale of 5 levels, where 0=absent, 1=low, 2=medium, 3=high, 4=very high.
A total score is calculated from the sum of the scores of all the 8 items and ranges from 0 (complaints absent) to 32 (very high severity).
Measured: Baseline and Week 16
Overall Assessment by the Investigator
The investigator recorded their impression of the overall clinical picture at the end of the treatment period (Week 16), taking into account the clinical picture compared with the Baseline visit. Data is reported for the percentage of participants in each of the following assessment categories: worsening, unchanged, discreet improvement or accentuated improvement.
Measured: Baseline and Week 16
Number of Participants With Adverse Events (AEs)
Adverse events are any unwanted medical occurrences in an individual taking part in a clinical study who is receiving a pharmaceutical product. The adverse event does not have necessarily a causal relationship with the treatment. In this definition, any adverse or unwanted signals and symptoms, or findings that appear from the start or that deteriorate during the clinical study are also included, i.e. any intercurrent diseases (recently diagnosed concomitant diseases or symptoms), accidents and clinically relevant changes in clinical laboratory values.
Measured: Baseline to Week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2013Sep 2015

First posted7 May 2013 (estimated)
Study startMay 2013
Primary completionSep 2015
Study completionSep 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Chronic Venous InsufficiencyStudies of the same condition, open and under way.
More trials run by TakedaThe 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 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 829 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01848210
Sponsor's protocol ID: VN01/12
Other IDs: U1111-1141-7277, 15030313.0.1001.5470
Status last verified: Sep 2016
First submitted: 2 May 2013
Last updated: 11 Nov 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Martinez-Zapata MJ, Vernooij RW, Simancas-Racines D, Uriona Tuma SM, Stein AT, Moreno Carriles RMM, Vargas E, Bonfill Cosp X. Phlebotonics for venous insufficiency. Cochrane Database Syst Rev. 2020 Nov 3;11(11):CD003229. doi: 10.1002/14651858.CD003229.pub4.
PubMed 33141449

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Chronic Venous Insufficiency trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Evaluation of Efficacy and Safety of the Fixed-dose Combination of Coumarin and Troxerutin (Venalot®) Versus Placebo in the Symptomatic Treatment of Chronic Venous Insufficiency - VENACT
ClinicalTrials.gov ID: NCT01848210
Acronym / sponsor ID: VN01/12
Conditions: Chronic Venous Insufficiency
Keywords: Drug therapy
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 829 participants (actual)
Lead sponsor: TakedaIndustry (pharma, biotech, devices)
Study start: May 2013
Primary completion: Sep 2015 (actual)
Study completion: Sep 2015 (actual)
First posted: 7 May 2013 (estimated)
Results: Posted 11 Nov 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to evaluate the efficacy and safety of the fixed-dose combination of coumarin and troxerutin versus placebo in the symptomatic treatment of chronic venous insufficiency.

Detailed description

Combination coumarin + troxerutin extended release tablets
Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient.

All participants will be asked to take two tablets three times a day throughout the study.

This multi-centre trial will be conducted in Brazil. The overall time to participate in this study is up to 18 weeks. Participants will make 6 visits to the clinic.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Coumarin 30 mg + Troxerutin 180 mg	Experimental	Drug: Coumarin/troxerutinCoumarin 30 mg, troxerutin 180 mg fixed-dose combination tablets, orally, three times daily for up to 16 weeks.
Placebo	Placebo comparator	Drug: PlaceboCoumarin + troxerutin placebo-matching tablets, orally, three times daily for up to 16 weeks.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Consent of subject or legal representative
Men or women of any ethnicity, aged between 18 and 75 years, and body mass index (BMI) equal or less than 40.
Is able to use properly the medication according to protocol.
Has chronic venous insufficiency in the reference leg with the clinical classification C3, or C4a orC4b or C5, provided that in two last situations the present lipodermatosclerosis does not compromise more than 1/3 portion of the leg immersed or immersible in the plethysmometer.
Has stable edema (in a steady state), equivalent to a variation lower than or equal to 10% in partial volume of the reference leg between the screening visit and the randomization visit, and present for at least 6 months.

Key exclusion criteria (24 listed)

Has chronic venous insufficiency classified as C1, C2 in the reference leg or C6 in any leg.
Has chronic venous insufficiency C4b or C5 in the reference leg, with lipodermatosclerosis present in more than 1/3 portion of the leg immersed in the plethysmometer.
Has unstable edema, equivalent to variation of more than 10% of partial volume in the reference leg between the screening visit and randomization visit, prior to start of treatment.
Has venous obstruction and/or deep vein thrombosis (DVT) and/or presence of phlebitis in lower limbs during the last 3 (three) months.
Has developed deep vein insufficiency during the last 3 (three) months.

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
Coumarin/troxerutinAlso: Venalot®Coumarin + troxerutin fixed-dose combination tablets	Drug	Coumarin 30 mg + Troxerutin 180 mg
PlaceboCoumarin + troxerutin placebo-matching tablets	Drug	Placebo

Primary outcome

Mean Change (Reduction) From Baseline in Volume of Reference Leg at Week 16
Time frame: Baseline and Week 16
Change in the partial volume of legs will be measured using a water plethysmometer. The volume of water (at 34 ± 0.2 °C) displaced after limb immersion is collected in an empty plastic Beaker which has been previously weighed (scale tare). The equilibrium/stability will be estimated using the absolute difference between measures of volume obtained at the Week 16 visit and Baseline to determine the reduction in edema.

3 secondary outcomes

Change (Reduction) From Baseline in Local Complaint Severity
Time frame: Baseline and Week 16
Overall Assessment by the Investigator
Time frame: Baseline and Week 16
Number of Participants With Adverse Events (AEs)
Time frame: Baseline to Week 16

Results and safety

Results posted to the registry on 11 Nov 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Coumarin + Troxerutin	411	323
Placebo	418	340

Primary outcome: Mean Change (Reduction) From Baseline in Volume of Reference Leg at Week 16

Time frame: Baseline and Week 16. Mean (Standard Deviation). Unit: milliliters (mL)

Measure	Coumarin + Troxerutin n = 333	Placebo n = 347
Value	1.13 (93.67)	5.78 (107.26)

Coumarin + Troxerutin vs Placebo: Mean Difference (Final Values): -4.65 (95% CI -19.81 to 10.51), p = 0.531, Regression, Linear

Population analysed: Participants from the ITT population, all eligible participants who received study drug and had at least one efficacy assessment at Visit 1 (28 ± 5 days after start of treatment), with data available for analysis.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the first dose of double-blind study drug and no more than 14 days (or 30 days for a serious adverse event) after the last dose of double-blind study drug.. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Coumarin + Troxerutin	3 of 394 (0.8%)	115 of 394 (29.2%)	Not reported
Placebo	2 of 398 (0.5%)	81 of 398 (20.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33141449Martinez-Zapata MJ, Vernooij RW, Simancas-Racines D, Uriona Tuma SM, Stein AT, Moreno Carriles RMM, Vargas E, Bonfill Cosp X. Phlebotonics for venous insufficiency. Cochrane Database Syst Rev. 2020 Nov 3;11(11):CD003229. doi: 10.1002/14651858.CD003229.pub4.

Related trials for Chronic Venous Insufficiency

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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.

Medical Director study director

Takeda

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Coumarin/troxerutin in people with Chronic Venous Insufficiency, run by Takeda.

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 7 inclusion and 24 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 11 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Mean Change (Reduction) From Baseline in Volume of Reference Leg at Week 16 (time frame: Baseline and Week 16). 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 NCT01848210, 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 11 Nov 2016; AzTrials last refreshed its copy on 8 Nov 2026.