Efficacy of MPFF 1000 mg oral suspension on CVD C0s-C1-related symptoms and quality of life.

BACKGROUND: To show the efficacy of micronized purified flavonoid fraction (MPFF) 1000 mg in the mild cases of chronic venous disorders (CVD), i.e. in C0s-C1 patients according to the CEAP classification. METHODS: In an international, randomized, double-blind, parallel-group study, symptomatic C0s to C4 patients according to the Clinical Etiological Anatomic Pathophysiologic (CEAP) were treated for 8 weeks by either MPFF 1000 mg once daily or MPFF 500 mg twice daily. The present post-hoc analysis is focused on the efficacy of MPFF at the daily doses of 1000 mg in the population of mild cases of the CVD (C0s-C1 patients) on lower limb discomfort, leg pain and leg heaviness using a 10-cm Visual Analog Scale (VAS), and on quality of life (QoL) using CIVIQ-20. RESULTS: In the 256 patients of the C0s-C1 subset of the study patients, lower limb discomfort improvement measured on VAS was clinically and statistically significant: -2.87±2.38 cm in the MPFF 1000 mg group and -3.30±2.36 cm in the MPFF 500 mg group (P<0.001 in both groups). Leg pain and leg heaviness VAS improved similarly: -2.77±2.58 cm in the MPFF 1000 mg group and -3.45±2.38 cm in the MPFF 500 mg group (P<0.001 in both groups), and -2.91±2.47 cm in the MPFF 1000 mg group and -3.47±2.33 cm in the MPFF 500 mg group (P<0.001 in both groups). The quality of life assessed by the CIVIQ-20 questionnaire improved significantly in both treatment groups from baseline to W8 with a mean changes of global index score of -16.53±14.18 in the MPFF 1000 mg group and -18.78±18.14 in the MPFF 500 mg group (P<0.001). CONCLUSIONS: MPFF at the daily dose of 1000 mg was shown to have a similar efficacy in mild CVD cases (C0s-C1 patients) as in the whole spectrum of patients from the main study, with a very good safety profile. These result further illustrates the interest of MPFF in the management of the mild cases of the disease at a daily dose of 1000 mg.

Understanding lower leg volume measurements used in clinical studies focused on venous leg edema.

The aim of this review was to discuss the different techniques of leg edema measurement that have been used in clinical trials to help determine the most appropriate method of assessment and quantification for use in future research. Venoactive drugs such as micronized purified flavonoid fraction (MPFF) are established agents for the treatment of venous leg edema, but results from randomized-controlled trials vary depending on the method of edema assessment. The medical literature was searched for published articles using the terms "venous lower limb edema" and "method of edema assessment." Clinical trials performed with MPFF used leg circumference and optometry for leg edema assessment. Indirect methods of lower limb volume assessment can be made by measurement of leg circumference with a tape or Leg-O-Meter. These are reliable and standardized instruments and simple and rapid to perform. Leg circumference measurements can also be used to indirectly estimate leg volume using the Frustum method. Direct methods such as water displacement volumetry are generally regarded as the gold standard for measurement of lower limb volume with low inter- and intra-individual variability. Nevertheless, to minimize variation in results measurement conditions must be standardized. The reproducibility of optometry can be considered good when positioning of the limb is appropriate. Other techniques also exist such as ultrasound imaging, bioelectrical impedance, tomodensitometry, Dual X-ray absorptiometry, computed tomography and magnetic resonance imaging. The different methods may be used to measure different compartments of the leg with or without the foot volume. For all techniques, strict standardization of measurement conditions is mandatory. Patient heterogeneity and method of edema assessment impact clinical trial results. In particular, there are a number of error sources with several methods of assessment that can lead to variability in trial results. Consequently, pilot studies are required to validate new methods of edema assessment using innovative technologies.

Clinical efficacy and safety of a new 1000-mg suspension versus twice-daily 500-mg tablets of MPFF in patients with symptomatic chronic venous disorders: a randomized controlled trial.

BACKGROUND: Chronic venous disorders (CVD) is estimated to affect 30% to 50% of women and 10% to 30% of men. The most widely prescribed treatment for CVD worldwide is micronized purified flavonoid fraction 500 mg (MPFF). The aim of this clinical trial was to develop a new once daily 1000-mg oral suspension of MPFF. METHODS: In an international, randomized, double-blind, parallel-group study, symptomatic individuals classified CEAP C0s to C4s were randomized in either treatment arm and treated for 8 weeks. Lower limb symptoms (discomfort, pain and heaviness) were assessed using Visual Analog Scales (VAS), and quality of life (QoL) was measured with the CIVIQ-20 Questionnaire. RESULTS: A total of 1139 patients were included in the study. Both MPFF treatment regimens were well tolerated and associated with a significant reduction in lower limb symptoms. A non-inferiority of MPFF 1000-mg oral suspension once daily compared to MPFF 500-mg tablet twice daily (P<0.0001) was found for lower limb discomfort (-3.33 cm for MPFF 1000 mg and -3.37 cm for MPFF 500 mg), leg pain (-3.27 cm for MPFF 1000 mg and -3.31 cm for MPFF 500 mg) and leg heaviness (-3.41 cm for MPFF 1000 mg and -3.46 cm for MPFF 500 mg). The patients' QoL was improved by about 20 points on the CIVIQ scale in both groups (19.33 points for MPFF 1000 mg and 20.28 points for MPFF 500 mg). CONCLUSIONS: MPFF 1000-mg oral suspension and MPFF 500-mg tablets treatments were associated with similar reductions in lower limb symptoms and QoL improvement. The new once daily MPFF1000-mg oral suspension has a similar safety profile to two tablets of MPFF 500 mg, with the advantage of one daily intake, potentially associated with improved patient adherence and easier CVD management.