The MUFFIN-PTS Trial

Sir Mortimer B. Davis - Jewish General Hospital

Status and phase: Active, not recruiting; Phase 3

Conditions: Post-Thrombotic Syndrome

Treatments: Drug: Placebo; Drug: Micronized Purified Flavonoid Fraction

Study type: Interventional

Funder types: Other

Identifiers

NCT03833024

332593-S1

Details and patient eligibility

About

In this randomized controlled trial (RCT), the investigators will determine whether a 6-month course of oral Micronized Purified Flavonoid Fraction (MPFF 1000 mg daily), compared with placebo, improves the symptoms and signs of the post-thrombotic syndrome (PTS) and quality of life (QOL) at 6 months follow-up.

Full description

The post thrombotic syndrome (PTS) is a form of secondary chronic venous insufficiency (CVI) that develops after a deep vein thrombosis (DVT). It affects up to 50% of patients after a proximal DVT (i.e. DVT involving popliteal vein or more proximal veins), and 5-10% of patients develop severe PTS. PTS is a chronic condition that reduces quality of life (QOL) and for which no curative treatment is available. Cornerstones of PTS treatment include the use of elastic compression stockings (ECS) to reduce leg symptoms and prevent PTS progression. However, ECS are incompletely effective, burdensome and costly to patients. Micronized Purified Flavonoid Fraction (MPFF, Venixxa), a venoactive drug, has been reported to be effective in reducing venous symptoms and signs and improving QOL in patients with CVI and has the potential to be effective for the treatment of PTS. Further, use of Venixxa is safe, with only few very mild and reversible reported side effects. However, studies of MPFF in patients with CVI have been of low to moderate quality, and there has been little use of this drug in North America. In addition, the effectiveness of MPFF has never been specifically evaluated in patients with PTS. Given that the pathophysiological mechanism of PTS is complex and unique (combination of obstructive and reflux mechanisms as well as inflammation), it is uncertain if MPFF is effective in patients with PTS, even if it may be effective for CVI more generally.

The MUFFIN-PTS study will be a multicentre (8-10 centres), randomized, placebo-controlled trial. Patients will be randomized (1:1 with stratification by centre) to receive 1000 mg of oral MPFF (Venixxa, one 500mg tablet BID) or an identically appearing placebo (one tablet BID) for 6 months, in addition to their usual PTS and DVT treatment (i.e. ECS and/or anticoagulation, at their treating physician's discretion). Its objectives are to evaluate the effectiveness and safety of MPFF (Venixxa) compared to placebo for the treatment of PTS.

86 patients with lower limb PTS will be enrolled in the study.

Enrollment: 88 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Villalta score ≥5 with at least two of the following four PTS manifestations (daily heaviness, cramps, pain, and objective edema) in the leg ipsilateral to a previous objectively diagnosed DVT, or DVT of unknown date but with presence of residual proximal or distal venous obstruction on ultrasound. Females of childbearing age must use medically approved method of birth control and must have negative pregnancy test results at the time of randomization.

Exclusion criteria

• Recent acute ipsilateral DVT (<3 months)
• Active ipsilateral venous ulcer
• Acute or chronic altered mental status
• Any venoactive drug intake within 3 months of the start of the study
• Allergy or hypersensitivity to MPFF/Venixxa
• Age<18 years
• Pregnant or breastfeeding women
• Life expectancy <1 year
• Refuse or unwilling to provide consent
• Unable to speak English or French
• Alcohol/drug abuse
• Hospitalized patients
• End-stage kidney disease (dialysis, creatinine clearance < 10ml/min)
• Liver cirrhosis Child-Pugh class C.
• Currently enrolled in other clinical trials, other than trials of prevention or treatment of venous thromboembolism

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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88 participants in 2 patient groups, including a placebo group

Venixxa

Active Comparator group

Description:

Micronized Purified Flavonoid Fraction (MPFF) for 6 months MPFF 500 mg, BID (morning and evening) for 6 months

Treatment:

Drug: Micronized Purified Flavonoid Fraction

Placebo

Placebo Comparator group

Description:

Placebo for 6 months 1 Tablet, BID (morning and evening) for 6 months

Treatment:

Drug: Placebo