WO2010037609A1 - Compression stocking for moderate to severe chronic venous insufficiency - Google Patents

Abstract

The invention relates to a compression stocking specifically designed for the treatment of symptomatic venous insufficiency classed as moderate, serious or severe (= C2 in the CEAP classification), composed of an elastic sleeve that is deformable in at least one direction and that is designed to exert a progressive pressure one at least one part of the region between the zone enveloping the ankle and the zone enveloping the calf, the zone enveloping the ankle having a low pressure of between 8 and 16 mm Hg at the smallest perimeter of the ankle (B), and the zone enveloping the calf having a high pressure of greater than 20 mm Hg at the greatest perimeter of the calf (C).

Description

 COMPRESSION LOW FOR MODERATE CHRONIC VENOUS INFECTIONS IN LOURDES

The invention relates to the treatment of chronic venous insufficiency.

Chronic venous insufficiency (CVI) includes all manifestations related to a functional or physical abnormality of the venous system caused by valvular incontinence with or without associated venous obstruction, sitting in the superficial veins and / or deep veins. This venous dysfunction can be congenital or acquired. Varicose veins, which are the most common expression, are visible dilated veins, corresponding to an anatomical network that is either well defined (systematized varices) or diffuse (non-systemized varices). They can be essential (most often) or acquired, linked in particular to an anomaly of the deep venous network. Varicose veins may be functionally dumb and express aesthetically or cause signs of CVI.

The true explanation is poorly understood. A genetic predisposition is indisputable. The triggering factors identified are: venous stasis caused by pregnancy, obesity, constipation, narcotics, sedentary lifestyle, prolonged standing. Dietary factors aggravate the deficiency related to the ground: the evolution of the food habits introduces an imbalance which favors the harmful peroxidation of the cell membranes veins. The functional signs are numerous, associated, paroxysmal, of variable intensity. They are typically aggravated by heat, prolonged standing or sitting stations, trampling and are improved by the cold and elevating position of the lower limbs. The most common are heaviness, pain, heaviness and cramps.

The complications are: - acute: ruptures, thromboses and edema

- chronic: dermatitis and hypodermatitis, oedemas, venous ulcers.

The treatment consists of: - prevention: avoid or limit prolonged standing still, sitting cross-legged or prolonged sitting, regular physical activity, elevate the bed to the feet, avoid prolonged exposure to thermal production , avoid overweight; venoactive or venotropic drugs; compression-compression; sclerotherapy surgery: ambulatory phlebectomy, cryosurgery (freezing of the vein with nitrogen), cryosclerosis of saphenous veins with consequent reflux or varicose veins of post-thrombotic venous syndrome, laser surgery.

The classical elastic compression (CE-Degr) currently prescribed in the treatment of moderate, severe and severe chronic venous insufficiency meets the principle of degressivity: the pressure is maximal in the ankle and then decreases when going up to the calf and the thigh, or "degressive compression". This principle is used regardless of the stage of venous insufficiency.

Although the effectiveness of CE-Degr for the prophylaxis of venous thromboembolism (VTE) after surgery has been the subject of a few publications compiled in a meta-analysis [1], data on the efficacy of EC-Degr Degr in the treatment of venous insufficiency especially postphlebitic are more reduced.

Only three studies evaluated the CE-Degr in the prevention of post-phlebitic symptom (PPS), which is prescribed immediately after a first episode of deep vein thrombosis (DVT) and for 2 years [2-3], ie in the year following a thrombotic episode [4].

The results of these studies are summarized in the following table:

Study Treatments compared CE-Degr Control n / N (%) n / N (%)

Brandjes CE-Degr versus 19/96 46/98

[2] no total SPP CE (20%) (47%)

30-40 mm Hg in ankle 11/96 23/98

Severe SPP

T7a7îd0rr ^""""" cT-De ^~ gT ^~ ___

[3] no total SPP EC (24%) (49%) 30-40 mm Hg in ankle 3/90 9/90

Severe SPP Ginsberg CE-Degr versus 0/24 1/23 Placebo total SPP (0%) (4.3%)

20-3 Omm Hg in ankle

Effect (Odds Ratio: OR = [0, 20 total of total SPP 0, 31 0, 48] CE-Degr OR = [0, 20

Severe SPP 0, 39 0, 76]

Given these results, CE-Degr with a pressure of 30 to 40 mmHg in ankle is recommended (grade IA) in the prevention of PPS after a first episode of DVT for a duration of 2 years [5].

Several European countries have published recommendations for elastic compression in chronic venous disease [6-7]. The degree of pressure is increasing according to the severity of the disease evaluated by the CEAP classification. For example, if we refer to the latest recommendations of the French Society of Phlebology [7], the pressure of a low shank (knee) expressed in millimeters of mercury at the level of the ankle (mm Hg) in relation to the pathologies or particular clinical situations is:

• Pressures of 10 to 20 mm Hg for: o COs, Cl (mild venous insufficiency) o C2 (a) (moderate venous insufficiency) with the sole objective of improving symptomatology,

• Pressures of 30 to 40 mm Hg for: o C2 (b) (moderate venous insufficiency) with the objective of improving symptomatology, curbing scalability and preventing complications of chronic venous disease, o C3, C4a, C4b, C5 (severe to severe venous insufficiency and for PPS).

These recommendations are made on the basis of a degressive elastic compression.

However, the principle of degressivity with higher ankle and lower calf and thigh pressures is debatable regardless of the stages of venous disease [8]. Indeed, the maximum volume of venous blood is contained in the calf and not in the ankle, even in the presence of edema. The perforating and muscular veins of the calf are quantitatively the most important and their anatomical topography favors venous stasis. On the other hand, the calf located at a distance from the heart and the lungs and subjected to the constraints of gravitation, behaves like a peripheral heart, the muscular contraction ensuring the venous or systolic emptying and the relaxation allowing the filling or diastole. The consequences of a malfunction of this calf muscle pump are the aggravation of functional signs and venous disease.

To combat this phenomenon, the pressures to be applied must be strong enough to cross all the anatomical structures and act on the superficial veins, but especially on the perforating, muscular and deep veins of the calf [8].

The inverse principle of degressive compression (CE-Degr), known as "progressive elastic compression" (CE-Prog), with lower ankle and stronger calf pressures has been described (see Figure 1 for CE-Degr and Figure 2). for CE-Prog). The patent EP 0 934 043 describes a progressive compression stocking for athletes with a progressive pressure of the ankle (7 to 13 mm Hg) to the calf (15 to 20 mm Hg). The adaptation of this type of progressive compression to the treatment of moderate to severe venous insufficiency was neither demonstrated nor predictable.

The inventors have just shown that progressive elastic compression with lower ankle and stronger calf pressures makes it possible to increase the effectiveness of the elastic compression compared with a conventional degressive elastic compression and thus to improve the treatment of venous insufficiencies. moderate to severe. In addition, they showed that progressive compression relieves the pain and heaviness associated with CVI.

On the other hand, the inventors have shown that progressive compression makes it possible to prevent venous ulcers and / or venous thromboses in moderate to severe venous insufficiency. In addition, the inventors have shown that the stockings according to the invention have a better comfort and a greater ease of donning and thus solve the problems of compliance encountered with conventional elastic compression stockings. The object of the present invention therefore relates to a compression stock specifically intended for the treatment of moderate, severe and severe symptomatic venous insufficiency (ï C2 in the CEAP classification) composed of an elastic sheath, deformable at least in one direction, shaped to exert a progressive pressure on at least a portion of the distance between the zone surrounding the ankle and the zone surrounding the calf, the zone surrounding the ankle having a low pressure at the smallest perimeter of the ankle (point B) between 8 and 16 mmHg, and the area surrounding the calf with a high pressure greater than 20 mmHg at the largest calf circumference (point C). These pressures stated above are measured according to standard NF G 30-102 part B.

The measuring points of the lower limb are defined by the European Commission Standards of Medical Compression Stockings (C. Gardon-Mollard, A. -A. Ramelet, The Medical Compression, Ed. Masson, ^2nd Edition).

The letter "a" corresponds to the sole of the foot and heel serving as a starting point for the measurement of height.

Capital letters correspond to a perimeter: - B Smallest perimeter of the ankle

- Bl Passage of the Achilles tendon in the twin muscles

- C Largest calf circumference of a normal conforming leg - D Tibial tuberosity level

- E Perimeter in the middle of the patella and popliteal fossa

- F Measuring point between K and E (mid-thigh measure)

- G 5 cm below K in vertical position (lower thigh)

H Gluteus at the widest point of the trochanters

- K Between-leg from a to the perineum

- T Natural size The letter δ, added by the plaintiff, corresponds to the perimeter of the upper end of the curve, located between 1 and 5 cm below the tibial tuberosity (D), for example 2 cm below D. The altitude δ can be such that the distance δ-D represents the total height of the reverse.

Advantageously, the pressure exerted by the bottom of the invention is progressive over the entire distance between the zone surrounding the ankle and the zone surrounding the calf (Figure 3).

Advantageously, the compression stocking of the invention is able to exert a decreasing pressure from the point

C to the point D, for example because this pressure decreases naturally due to a lower calf curve between the point C and the point D.

Above point C, the compression stocking of the invention is capable of exerting a pressure of less than 20 mmHg. At point D, the compression stocking of the invention is capable of exerting a pressure of between 8 and 16 mmHg.

Under the term "elastic compression stockings" we mean all sizes or executions such as stockings, thighs, thighs, tights, maternity tights, man tights, pantyhose, sleeves.

The CEAP classification is described in Table 1 below.

Table 1: CEAP classification

The elastic compression stockings according to the invention in the case of a low hock for example may have a lapel in the upper part, above the area surrounding the calf. According to this embodiment, the bottom of the invention is able to exert in this area above δ a lower pressure than that at the calf thus avoiding a tourniquet effect popliteal example.

According to this embodiment again and advantageously, the compression stocking of the invention exerts a degressive pressure from the point C towards the point δ and a still decreasing pressure from the point δ towards the point D (See

Figure 4).

Preferably, the bottom is able to exert at the point D a pressure of between 8 and 16 mm Hg. For example, this pressure is between 8 and 10 mm Hg.

Preferably, the compression-compression stocking device according to the invention is capable of exerting a pressure of between 20 and 25 mmHg at point C (see FIG. 3). In a particularly preferred manner, the compression-compression stocking device according to the invention is capable of exerting a pressure of about 23 mmHg ± 2 mm at point C.

According to a preferred embodiment, the compression stocking according to the invention is capable of exerting a pressure of between 8 and 12 mmHg at point B.

The compression stocking may also have an envelope comprising an upper portion from the point

D enveloping the knee and thigh with a pressure of less than 20 mm Hg and preferably between 5

16 mm Hg at the level of the thigh. The maximum value of the compression of a bottom according to the invention is at point C. On either side of this point, the value of the pressure decreases.

According to a particular embodiment, the product will apply:

• a pressure of 23 + 2 mm Hg at point C,

• a pressure of between 8 and 12 mm Hg at the ankle at point B,

• a progressive pressure from B to C, • a pressure of between 20 and 25 mm Hg at point C,

A degressive pressure from C to δ,

• a pressure of between 14 and 22 mm Hg at point δ,

• a degressive pressure of δ to D and

• a pressure between 8 and 16 mm Hg at point D. The actual pressure profile depends on the morphology of the wearer of the stocking and in particular on the shape of the calf circumference and the height of the half-leg, since the value of the compression exerted by the bottom is defined by the elastic reaction of the bottom as a consequence of its deformation by the leg of the wearer.

The pressure profile exerted by the compression stock according to a particular embodiment of the invention is between the two limit profiles schematically represented in FIG. 3.

Another object of the present invention relates to the use of the stockings according to the invention for the treatment of moderate, severe and severe symptomatic venous insufficiency (≥ C2 in the CEAP classification). More particularly, "moderate, severe and severe symptomatic venous insufficiency (≥ C2 in the CEAP classification)" includes symptomatic varicosis with disabling functional impact, primary or secondary valvular reflux of the deep and / or muscular and / or perforating and / or communicating and / or superficial veins, sequelae of deep vein thrombosis, muscular and superficial lower extremities, syndromes of hyperdistensitivity or venous hyperpressure , or some superficial or deep venous malformations.

Another object of the present invention relates to the use of the stockings according to the invention for the treatment of stabilized lymphedema, apart from an acute attack.

The invention also relates to the use of the stockings according to the invention for the treatment of lipoedema, apart from an acute attack.

The invention also relates to the use of the stockings according to the invention for the treatment of hypodermitis or lymphangitis, at a distance from the acute phase.

Another subject of the present invention relates to a method for treating moderate, severe and severe symptomatic venous insufficiency (≥ C2 in the CEAP classification) comprising the wearing of two stockings according to the invention by a patient presenting such a pathology for at least 6 months. hours a day, preferably eight hours a day. Preferably, the patient must wear the stockings according to the invention over a period of at least 3 months, preferably 6 months.

Another object of the present invention relates to a stocking according to the invention for the treatment of moderate, severe and severe symptomatic venous insufficiency (≥ C2 in the CEAP classification).

The product may be manufactured according to the embodiments known to date for woven, non-woven, knitted or other textiles. The product can be obtained either directly at the output of the machine (example knitting small diameter according to the techniques of mesh socks and fashion socks or meshing techniques compression stockings), or by cutting and assembly of piece of fabric. For woven products for example all types of armor can be used.

This product can use all chemical raw materials, artificial, natural known to date (eg elastane, polyamide, polyester, cotton, wool, linen, silk, ...), alone or in combination. Preferably, elastane, polyamide and / or cotton are used.

According to a preferred embodiment, the son used are yarns wrapped with an elastic central portion and one or more coatings (see Figure 6).

The mesh used for bottom knitting according to the invention may be of the same type as that of conventional compression-compression stockings, for example of screen type, jersey, pinched or floated micromesh, etc., or any mesh known in itself. even knitting specialists. Preferably, the mesh used is a knit stitch with a knit yarn with, after each knitted row, the inclusion of a weft yarn (see FIG. 5).

Zone force and force gradient control is a combination of parameters such as the amount of weft yarn and the distance between each weft yarn given by the knit yarn. The skilled person will adjust according to his general knowledge these parameters to obtain a low according to the invention.

figures Figure 1 shows the degressive compression.

Figure 2 schematizes two pressure limit profiles exerted by Progressive Compression.

Figure 3 schematizes the two pressure profiles exerted by the progressive compression according to the invention.

Figure 4 shows schematically the two pressure profiles exerted by the progressive compression according to the invention with lighting of the decrease of the pressure at the back in the area above the point δ.

Figure 5 schematizes the parts of a low hock.

Figure 6 schematizes the bottom grid of Example 2. Figure 7 shows the gimped son. A: simple gimped. B: double gimped.

The present invention is illustrated by the following examples.

EXAMPLES

Example 1: Clinical Study in Patients with Moderate, Significant, or Severe Chronic Venous Insufficiency (C2bS, C3S, C4S, C5S)

The CE-Prog study was a national multicentre randomized study in two parallel and double-blind groups with the following products:

• Degressive elastic compression (CE-Degr) by low hock, corresponding to the standards of the Institut Français du

Textile and Clothing (IFTH) with an average pressure of 30 mmHg in ankle (100%) and 21 mmHg compared to the calf (70%). • Progressive elastic compression (CE Prog) by lower hock, corresponding to an average pressure of 10 mm Hg in ankle and 23 mm Hg facing the calf (according to NF G 30-102 part b). Its main objective was to demonstrate, at 3 months, the superiority of CE-Prog in patients with moderate, severe or severe symptomatic chronic venous insufficiency (C2bS, C3S, C4S, C5S) in terms of: • improvement of symptoms typical of chronic venous insufficiency and events (absence of venous ulcer or superficial and / or deep venous thrombosis of the lower limbs), • and absence of venous ulcer or superficial and / or deep venous thrombosis of the lower limbs.

Its secondary objectives were to demonstrate the superiority of progressive compression in terms of ease of donning and discomfort.

The duration of participation for a patient was 6 months.

The inclusion criteria were as follows: major patient with chronic symptomatic venous insufficiency (moderate, severe or severe) defined by the CEAP classification: C2bS - C3S - C4S - C5S, Ec - Ep -

Es - En, As - Ad - Ap - An, Pr - Po - Pn justifying a degressive compression of 30 mm Hg in ankle according to the recommendations of the SFP [7], suffering from heaviness and pain in the lower limbs, with a score of

Rutherford between 3 and 12.

Results Patients of the study

401 patients were included in 44 French centers and randomized in this study.

The main analysis focused on all patients included in the trial according to the ITT principle.

Both treatment arms were comparable to inclusion. The analysis of the demographic characteristics showed a homogeneous population, the average age being 52.6 ± 14.2 years and 75.3% of the patients being women. The analysis of the initial clinical characteristics also showed a homogeneous population, with a majority of patients (65.6%) at the C3 stage of IVC (venous edema), all patients except one with varicose veins, and a Modified Rutherford excluding medial contention and ulcers of 5. concomitant CVD-specific drug treatments were similarly distributed in both groups.

Patients in both groups were very observant, with the vast majority of patients (> 80% in each group) wearing socks from sunrise to bedtime or most of the time, throughout the 6 months of treatment.

Main performance criterion

At 3 months, 70.2% of patients in the CE-Prog group and

59.6% of patients in the CE-Degr group were successful in treatment; 29.8% of patients in the group

CE-Prog and 40.4% of patients in the CE-Degr group experienced treatment failure at 3 months. This difference represents a statistically significant 26% reduction in the CE-Prog failure rate compared to the CE-Degr (p = 0.030).

The results of the criteria composing the main criterion, occurrence of clinical thromboembolic events and clinical symptoms (pain, heaviness) of venous insufficiency at 3 months, were both in favor of CE-Prog.

A significant difference between the two groups was observed in patients with stage C3 CVI at baseline, with a 24% failure rate reduction with CE-Prog (p = 0.023). In the most severe CVI stages, C4 and C5, the difference in failure rate between the two groups (48%), in favor of the CE-Prog, is close to the statistical significance threshold (p = 0.055). Secondary performance criteria

No significant difference was observed between CE-Prog and CE-Degr on the following secondary endpoints: occurrence of clinical events (including varicose ulcers), improvement of pain / heaviness sensations at 1 month and 6 months , and improvement of the Rutherford score modified at 3 months.

On the other hand, the CE-Prog proved to be much superior to the CE-Degr in terms of ease of donning socks, with a significant difference of 71% at 1 month (p <0.0001) and 63% 3 months ( p <0.0001). Moreover, this result in favor of the EC-Prog remains confirmed after 6 months of follow-up (86.2% against 57.1% - p <0.0001).

Conclusion: The CE-Prog study shows that progressive compression is more effective than degressive compression in the management of moderate or severe chronic venous insufficiency whatever the initial severity of this venous insufficiency. This result observed at 3 months on clinical criteria in a double-blind study is not related to differences in treatment compliance, even though progressive compression is significantly easier to put on than degressive compression. In terms of tolerance, the most commonly observed problems were feelings of constriction and tightness and some serious adverse events occurred during the study, with no significant difference, however, between the two types of compression. The effectiveness of the CE-Prog should be increased even more in the general population especially with a better observance insofar as it is easier to put on.

Example 2: Manufacture of a stocking according to the invention having a pressure of 21 to 25 mmHg in the zone surrounding the calf and from 8 to 16 mmHg in the zone surrounding the ankle

The socks made according to this invention consist of: a lapel portion, a leg portion, a knitted heel, a foot portion and a seam-closed tip (see Figure 4).

The type of mesh retained for the production of this stocking is a jersey stitch with a knit yarn with, after each knitted row, the inclusion of a weft yarn (see FIG. 5).

The yarns used are yarns wrapped with an elastic central part and one or more coating (see Figure 6).

The materials used are elastane and polyamide.

Zone force and force gradient control is a combination of the components, the amount of weft yarn and the distance between each weft yarn given by the knitting yarn.

The definition of pressure is itself a resultant of the applied voltage for a given application dimension and will respond to Laplace's law: P = T / r

P: Pressure T: Voltage developed by the product at application r: Application radius

The pressure is considered for a circular radius of application.

REFERENCES

1. Wells PS, Lensing AW, Hirsh J et al. Graduated compression stockings in the prevention of post-operative venous thromboembolism. Arch Intern Med 1994; 154: 67-72.

2. Brandjes DP, Buller HR, Heijboer H, et al. Randomized trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet 1997; 349: 759-762.

3. Prandoni P. Below-Knee compression stockings for the prevention of pst-thrombotic syndrome: a randomized study [abstract]. Patophysiol Haemost Thromb 2002; 32 (suppl 2): 72. 4. Ginsberg JS, Hirsh J, Julian J, et al. Prevention and treatment of postphlebitic syndrome: results of a 3-part study. Arch Intern Med 2001; 161: 2105-2109.

5. Buller HR, Agnelli G, Hull RD, et al. Antithrombotic therapy for venous thromboembolic disease. The seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004, 126: 401S-428S.

6. Guidelines on compression by the German Society of Phlebology. Dermatol Surg 2004; 30: 687-93.

7. Cornut-Thenard A, Benigni JP, UhI JF, Floch E, Rastel D, Moyou-Mogo R, Parpex P, Fardon Moral C. Recommendations of the French Society of Phlebology on the daily use of compressive therapy. Phlebology 2006; 59 (3): 237-244.

8. Couzan S, Prufer M, Ferret JM, Mismetti P, Pouget JF. A new concept of compression - compression: contribution of the color doppler with venous pressure and MRI. Phlebology 2002; 55: 159-71.

Claims

claims 1. Compression stockings specifically intended for the treatment of moderate, severe and severe symptomatic venous insufficiency (≥ C2 in the CEAP classification) characterized in that it consists of an elastic sheath, deformable at least in one direction, and shaped to exert progressive pressure on at least a portion of the distance between the ankle wrapping area and the calf wrapping area, said ankle wrapping area having a low pressure of between 8 and 16 mm Hg at the smallest perimeter of the ankle (B ), and said calf wrapping area having a high pressure greater than 20 mm Hg at the largest calf circumference (C). 2. compression stocking according to claim 1, characterized in that the pressure is progressive over the entire distance between the zone surrounding the ankle and the zone surrounding the calf. 3. The compression stocking according to any one of the preceding claims, characterized in that it is able to exert a pressure in the area above the largest perimeter of the calf (> C) less than 20 mm Hg. 4. The compression stocking according to any one of the preceding claims, characterized in that it is capable of exerting a pressure of between 8 and 16 mm Hg below the knee (D). 5. The compression stocking according to any one of the preceding claims, characterized in that it is capable of exerting a pressure of between 20 and 25 mm Hg at the largest perimeter of the calf (C). 6. compression stocking according to any one of the preceding claims, characterized in that it is capable of exerting a pressure of about 23 mm Hg ± 2 mm at the largest perimeter of the calf (C). 7. compression stocking according to any one of the preceding claims, characterized in that it is capable of exerting a pressure of between 8 and 12 mm Hg in the region surrounding the ankle (B). 8. compression stocking according to any one of the preceding claims, characterized in that the envelope comprises an upper part enveloping the knee and the thigh capable of exerting a pressure of less than 20 mm Hg, preferably 5 to 16 mm Hg. 9. Stock according to any one of claims 1 to 8 for its use in the treatment of moderate, severe and severe symptomatic venous insufficiency (≥ C2 in the CEAP classification). 10. Bottom according to claim 9 for its use in the treatment of symptomatic varicosis with disabling functional impact, primary or secondary valvular reflux of deep veins and / or muscle and / or perforating and / or communicating and / or superficial, sequelae of deep vein thrombosis, muscular and superficial lower extremities, syndromes of hyperdistensitivity or venous hyperpressure, or certain superficial or deep venous malformations. 11. Stock according to any one of claims 1 to 8 for its use in the treatment of stabilized lymphedema, apart from acute attack. 12. Stock according to any one of claims 1 to 8 for its use in the treatment of lipoedema, apart from acute attack. 13. Stock according to any one of claims 1 to 8 for its use in the treatment of hypodermitis or lymphangitis, remote from the acute phase.