NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE

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1 NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE INTERVENTIONAL PROCEDURES PROGRAMME Interventional procedure overview of endovenous mechanochemical ablation for varicose veins Treating varicose veins using a rotating wire and an injected chemical Varicose veins are veins that have become wider than normal and are unable to transport blood properly so that blood collects in them. This can cause heaviness, aching, throbbing, itching, cramps and fatigue in the legs. In severe cases, patients may develop skin discoloration or inflammation, and skin ulcers. In endovenous mechanochemical ablation, a tube with a rotating hollow wire at its tip is inserted into the affected vein in the leg. As the tube is pulled back out of the vein, the wire is rotated, damaging the lining of the vein. At the same time, a chemical is injected through the hollow wire into the vein. This causes the vein to become inflamed, then shrivel and close. Introduction The National Institute for Health and Clinical Excellence (NICE) has prepared this overview to help members of the Interventional Procedures Advisory Committee (IPAC) make recommendations about the safety and efficacy of an interventional procedure. It is based on a rapid review of the medical literature and specialist opinion. It should not be regarded as a definitive assessment of the procedure. Date prepared This overview was prepared in May 2012 and updated in November Procedure name Endovenous mechanochemical ablation for varicose veins Specialist societies British Society of Interventional Radiology The Vascular Society of Great Britain and Ireland Page 1 of 16

2 Description Indications and current treatment Varicose veins are a sign of underlying venous insufficiency and affect 20 30% of adults. Most people with varicose veins have no symptoms, but venous insufficiency may cause fatigue, heaviness, aching, throbbing, itching and cramps in the legs. Chronic venous insufficiency can lead to skin discoloration, inflammatory dermatitis and ulceration. Long (or great) saphenous vein insufficiency is the most common form of venous insufficiency in people presenting with symptoms. Because most varicose veins do not cause serious health problems, treatment is not usually needed on medical grounds. Conservative methods such as compression hosiery (support stockings or tights) may help people with symptomatic varicose veins. If symptoms are severe the main treatment options include sclerotherapy, endovenous laser treatment, radiofrequency ablation and surgery (usually stripping and ligation of the long and short saphenous veins, and phlebectomies). What the procedure involves Endovenous mechanochemical ablation for varicose veins combines mechanical and chemical ablation to close veins without the need for tumescent anaesthesia (infusion of a large volume of dilute local anaesthetic around and along the entire length of vein to be treated). The procedure is carried out using local anaesthesia at the catheter insertion site. Ultrasound imaging is used to identify the target vein (usually the long saphenous vein), its diameter and the treatment length, which depends on perforators and tributaries. An infusion catheter with a motor drive is introduced percutaneously into the distal end of the target vein and, in the case of the long saphenous vein, the catheter tip is advanced to the saphenofemoral junction. A dispersion wire that extends through the catheter lumen is rotated to damage the epithelium and a sclerosant is infused simultaneously as the catheter is slowly pulled back through the vein. After the procedure, ultrasound may be used to check for target vein occlusion and patency of the common femoral vein. Patients are advised to wear compression stockings for approximately 2 weeks after the procedure. Clinical assessment The CEAP (clinical, etiological, anatomic and pathophysiologic) classification from the American Venous Forum is often used to classify venous disease of the lower limb. Clinical signs are classified as: C0 no signs of venous disease; C1 telangiectases or reticular veins; C2 varicose veins; C3 oedema; C4a pigmentation or eczema; C4b lipodermatosclerosis or atrophie blanche; C5 healed venous ulcer; C6 active venous ulcer. Page 2 of 16

3 Literature review Rapid review of literature The medical literature was searched to identify studies and reviews relevant to endovenous mechanochemical ablation for varicose veins. Searches were conducted of the following databases, covering the period from their commencement to 25 September 2012: MEDLINE, PREMEDLINE, EMBASE, Cochrane Library and other databases. Trial registries and the Internet were also searched. No language restriction was applied to the searches (see appendix C for details of search strategy). Relevant published studies identified during consultation or resolution that are published after this date may also be considered for inclusion. The following selection criteria (table 1) were applied to the abstracts identified by the literature search. Where selection criteria could not be determined from the abstracts the full paper was retrieved. Table 1 Inclusion criteria for identification of relevant studies Characteristic Publication type Patient Intervention/test Outcome Language Criteria Clinical studies were included. Emphasis was placed on identifying good-quality studies. Abstracts were excluded where no clinical outcomes were reported, or where the paper was a review, an editorial, or a laboratory or animal study. Conference abstracts were also excluded because of the difficulty of appraising study methodology, unless they reported specific adverse events that were not available in the published literature. Patients with varicose veins. Endovenous mechanochemical ablation. Articles were retrieved if the abstract contained information relevant to the safety and/or efficacy. Non-English-language articles were excluded unless they were thought to add substantively to the English-language evidence base. List of studies included in the overview This overview is based on approximately 60 patients from 2 case series and 6 case reports 1 3. Other studies that were considered to be relevant to the procedure but were not included in the main extraction table (table 2) have been listed in appendix A. Page 3 of 16

4 Table 2 Summary of key efficacy and safety findings on endovenous mechanochemical ablation for varicose veins Abbreviations used: CEAP, clinical, etiological, anatomical and pathophysiologic elements classification; DVT, deep vein thrombosis; GSV, great saphenous vein; IQR, interquartile range Study details Key efficacy findings Key safety findings Comments Elias S (2012) 1 Case series USA Recruitment period: 2009 Study population: patients with significant GSV reflux n=29 patients (30 veins) Mean age: 54 years (range 31 90) Sex: 60% female Mean length of treated vein: 37.5 cm (range 24 47) Patient selection criteria: Reflux as documented by ultrasound extending for 0.5 seconds or longer. CEAP Class 1 patients were excluded. Other exclusion criteria were acute DVT, immobility, anticoagulation and GSV diameters >12 mm. Technique: Clarivein system (Vascular Insights LLC, Madison, USA) was used with 1.5% liquid sodium tetradecyl sulphate. Procedures were limited to the GSV. No secondary treatments used. Mean follow-up: 9 months (range days) Conflict of interest/source of funding: The research was sponsored in part by Vascular Insights LLC. Number of patients analysed: 29 (30 veins) Average treatment time=14 minutes Primary closure rate at mean follow-up of 260 days (based on ultrasound)=96.7% (29/30) One vein recanalised between the 1-week and 1-month visits (recanalisation was seen on ultrasound but the treated vein was not refluxing). Patients did not complain of pain during the procedure. Three minor thigh ecchymoses were observed at levels where the rotating wire may have caught on a valve cusp or vein wall. No DVT, nerve or skin injury occurred. No patient complained of paraesthesia, hypoaesthesia or motor dysfunction. Follow-up issues: There were no losses to followup. Study design issues: The primary objectives of the study were to determine the overall safety of the procedure and to define recanalisation of treated veins at 6 months. Study population issues: 77% of patients were in Class 2 according to the CEAP classification, 7% were in Class 3 and 16% were in Class 4a. Page 4 of 16

5 Abbreviations used: CEAP, clinical, etiological, anatomical and pathophysiologic elements classification; DVT, deep vein thrombosis; GSV, great saphenous vein; IQR, interquartile range Study details Key efficacy findings Key safety findings Comments Van Eekeren R (2011) 2 Case series The Netherlands Recruitment period: not stated Study population: patients with varicose veins and primary GSV incompetence n=25 patients (30 veins) Mean age: 52 years Sex: 72% (18/25) female Mean length of treated vein: 40 cm Patient selection criteria: age over 18 years; C2 C6 varicose veins; primary GSV incompetence (reflux was defined as retrograde flow of >0.5 seconds after calf compression measured in an upright position). Exclusion criteria included pregnancy and lactation, allergy or contraindication to the sclerosant, previous surgical treatment of varicose veins, history of DVT, anticoagulation, severe tortuosity of the GSV, and GSV diameters less than 4 mm or greater than 12 mm measured in the supine position. Technique: Clarivein system (Vascular Insights LLC, Madison, USA) was used with 1.5% polidocanol. Procedures were limited to the GSV. Mean follow-up: 6 weeks Conflict of interest/source of funding: 1 of the authors was Principal Investigator for the US clinical study that was sponsored in part by Vascular Insights LLC. Number of patients analysed: 25 (30 veins) Average treatment time=20 minutes Technical success Initial technical success (occlusion identified by ultrasound)=100% Recanalisation Complete occlusion at 6 weeks=87% (26/30) of veins (assessed by duplex ultrasound). Two patients had partial recanalisation of the proximal GSV 15 and 18 cm, respectively, from the saphenofemoral junction; 1 patient had partial recanalisation of the distal GSV. One patient had total recanalisation of the GSV, which was successfully treated by a repeat procedure at 7 weeks after initial treatment. Median venous clinical severity score (scale 0 30, lower scores indicating less severe disease) Baseline=3.0 (IQR ) 6 weeks after the procedure=1.0 (IQR ), p<0.001 In 1 patient with superficial phlebitis, the venous clinical severity score worsened from 5 to 11. Patient satisfaction After 6 weeks, median patient satisfaction=8.5 (IQR 8 9, on a scale of 0 10) No major adverse events were observed. There was no deep vein thrombosis, nerve injury, skin necrosis, infection, or hyperpigmentation. Minor complications : localised ecchymosis at the puncture site=30% (9/30) transient superficial phlebitis of distal tributaries (resolved within a week)=13% (4/30) During the procedure, the median maximal pain score was 4 (on a scale of 0 10). On day 1 after the procedure, the mean maximal pain was 9 mm (on a scale of mm), which decreased to 2 mm at 7 days after the procedure. All 4 patients with superficial phlebitis had prolonged pain for >1 week. At 6 weeks, no additional complications were observed clinically or with duplex ultrasonography. Follow-up issues: There were no losses to followup. Study design issues: The primary outcome measures were immediate occlusion and postprocedural complications. Pain was measured during the procedure using a scale of 0 10 (where 0 indicated no pain). After the procedure, a visual analogue scale of mm was used. Patient satisfaction was determined on a scale of 0 10, with higher scores indicating greater satisfaction. The venous clinical severity score includes 9 clinical characteristics of chronic venous disease, measured on a scale of Study population issues: 60% (18/30) of veins were in Class 2 according to the CEAP classification, 30% (9/30) were in Class 3 and 10% (3/30) were in Class 4. Five patients had bilateral GSV insufficiency. Other issues The authors note that they have changed several aspects of the procedure following the results of this initial series of patients (including an increase in the concentration of sclerosant). Page 5 of 16

6 Abbreviations used: CEAP, clinical, etiological, anatomical and pathophysiologic elements classification; DVT, deep vein thrombosis; GSV, great saphenous vein; IQR, interquartile range Study details Key efficacy findings Key safety findings Comments FDA (MAUDE database) 3 Case reports Report dates: adverse events reported in relation to the use of Clarivein Infusion catheter (Vascular Insights LLC) 4 of the 6 events occurred after treatment of the short saphenous vein (events 1,2,3 and 5). 1. At the first post-procedure followup, venous duplex ultrasound showed a clot in the right popliteal vein. The patient was asymptomatic and was treated conservatively. 2. Four days after the procedure, venous duplex ultrasound showed a left popliteal DVT. The patient was asymptomatic and was treated conservatively. 3. Four days after the procedure, venous duplex ultrasound showed a right popliteal DVT with clot adherent to the vein wall. The patient was treated conservatively. Follow-up ultrasound showed no further propagation of DVT and the patient remains asymptomatic. 4. Three days after the procedure, the patient developed shortness of breath, left-sided pain on inspiration, and marked fatigue. She was treated for CT-confirmed pulmonary embolism and subsequently discharged from hospital with a good prognosis. 5. At the first postprocedure follow-up, venous duplex ultrasound showed subocclusive acute thrombus. The patient was asymptomatic and was treated conservatively. At a second follow-up, the patient was asymptomatic. The clot was still present but had retracted. 6. At the first postprocedure follow-up, venous duplex ultrasound showed DVT. The patient was asymptomatic and was treated conservatively. Page 6 of 16

7 Efficacy Occlusion rates A case series of 29 patients reported a primary closure rate of 97% (29/30 veins) at a mean follow-up of 260 days (assessed by ultrasound) 1. A case series of 25 patients reported complete occlusion in 87% (26/30) of veins at 6-week follow-up (assessed by duplex ultrasound) 2. In this case series, 3 patients had a partial recanalisation and 1 patient had a total recanalisation (which was successfully treated by a repeat procedure 7 weeks after the initial procedure). It should be noted that the 2 case series used different sclerosants. Venous clinical severity score The case series of 25 patients reported a statistically significant reduction in median venous clinical severity score (scale 0 30, higher scores indicating more severe disease) from 3 (interquartile range 2 5) at baseline to 1 (interquartile range 0.3 3) at 6-week follow-up (p<0.001) 2. Patient satisfaction The case series of 25 patients reported a median patient satisfaction score of 8.5 (scale 0 10, higher scores indicating increased patient satisfaction) 2. Safety Deep vein thrombosis Deep vein thrombosis after the procedure was reported in 4 patients (reports submitted to the Food and Drug Administration [FDA] manufacturer and user facility device experience [MAUDE] database); 3 of these thromboses occurred after treatment of the short saphenous vein 3. All 4 patients were asymptomatic and were treated conservatively. Pulmonary embolism Pulmonary embolism after the procedure was reported in 1 patient (report submitted to the FDA MAUDE database) 3. After treatment, the patient was discharged from hospital with a good prognosis. Ecchymosis Minor thigh ecchymosis was reported in 10% (3/30) of limbs in the case series of 29 patients 1. Localised ecchymosis at the puncture site was reported in 30% (9/30) of limbs in the case series of 25 patients 2. Page 7 of 16

8 Phlebitis Transient superficial phlebitis of distal tributaries was reported in 13% (4/30) of limbs in the case series of 25 patients 2. Validity and generalisability of the studies The evidence consists of 2 small case series with short-term follow-up. The 2 studies used different sclerosants; the type and concentration of sclerosant is likely to have an effect on the efficacy of the procedure. Both the studies report results from the initial series of patients treated by the procedure at the study centres. Existing assessments of this procedure There were no published assessments from other organisations identified at the time of the literature search. Related NICE guidance Below is a list of NICE guidance related to this procedure. Appendix B gives details of the recommendations made in each piece of guidance listed. Interventional procedures Ultrasound-guided foam sclerotherapy for varicose veins. NICE interventional procedure guidance 314 (2009). Available from Endovenous laser treatment of the long saphenous vein. NICE interventional procedure guidance 52 (2004). Available from Transilluminated powered phlebectomy for varicose veins. NICE interventional procedure guidance 37 (2004). Available from Radiofrequency ablation of varicose veins. NICE interventional procedure guidance 8 (2003). Available from Specialist Advisers opinions Specialist advice was sought from consultants who have been nominated or ratified by their Specialist Society or Royal College. The advice received is their individual opinion and does not represent the view of the society. Mr M Gaunt (British Society of Interventional Radiology); Mr E Chaloner, Mr I Franklin, Mr T Lees, Mr I Nyamekye, Professor R Sayers, Professor M Thompson (The Vascular Society) Page 8 of 16

9 Three Specialist Advisers perform the procedure regularly; 4 have never performed the procedure. Three Specialist Advisers described the procedure as the first in a new class of procedure, 2 described it as a minor variation of an existing procedure, 1 described it as established practice and 1 described it as novel and of uncertain safety and efficacy. The comparators would be conventional open surgery, endovenous thermal ablation (radiofrequency or laser), and liquid or foam sclerotherapy. One Specialist Adviser reported that he had seen 2 cases of deep vein thrombosis, both in patients having short saphenous veins treated, and has since stopped treating short saphenous veins. Adverse events reported in the literature include ecchymosis and phlebitis. Additional theoretical adverse events include visual and neurological disturbance, allergy to sclerosant, haemorrhage, infection, embolisation, vein wall perforation and skin pigmentation. Key efficacy outcomes include vein occlusion (up to 5 years after treatment), absence of full or partial recanalisations after the treatment (seen on duplex scan but not necessarily clinically apparent), length of treated truncal vein occluded by initial treatment, reduction of clinical symptoms, improved periand post-procedural pain scores and improved quality of life. There are no data on long-term vein occlusion rates. Two Specialist Advisers noted that a UK trial is due to start shortly (at Charing Cross Hospital). One Specialist Adviser noted that there are uncertainties with regard to the incidence and extent of recanalisation of treated truncal veins at 1 and 2 years and the clinical significance of this. Three Specialist Advisers considered the procedure to have a potentially moderate impact on the NHS, in terms of patients and use of resources; 2 Specialist Advisers thought the impact would be minor. Patient Commentators opinions NICE s Patient and Public Involvement Programme was unable to gather patient commentary for this procedure. Issues for consideration by IPAC None other than those described above. Page 9 of 16

10 References 1. Elias S, Raines JK (2012) Mechanochemical tumescentless endovenous ablation: final results of the initial clinical trial. Phlebology 27: van Eekeren RRJP, Boersma D, Elias S et al. (2011) Endovenous mechanochemical ablation of great saphenous vein incompetence using the ClariVein device: a safety study. Journal of Endovascular Therapy 18: Food and Drug Administration (FDA). Manufacturer and user facility device experience (MAUDE) database. Available from: sttimeout=500 [accessed 13 June 2012] Page 10 of 16

11 Appendix A: Additional papers on endovenous mechanochemical ablation for varicose veins There were no additional papers identified. Page 11 of 16

12 Appendix B: Related NICE guidance for endovenous mechanochemical ablation for varicose veins Guidance Interventional procedures Recommendations Ultrasound-guided foam sclerotherapy for varicose veins. NICE interventional procedure guidance 314 (2009). 1.1 Current evidence on ultrasound-guided foam sclerotherapy for varicose veins shows that it is efficacious in the short term. The evidence on safety includes systemic side effects in some patients. Therefore, this procedure should only be used with special arrangements for clinical governance, consent and audit. 1.2 Clinicians wishing to undertake ultrasound-guided foam sclerotherapy for varicose veins should take the following actions. Inform the clinical governance leads in their Trusts. Ensure that patients understand the potential side effects of the procedure, including those thought to be associated with foam embolisation, and provide them with clear written information, which should include other treatment options. In addition, the use of NICE s information for patients ( Understanding NICE guidance ) is recommended (available from Audit and review clinical outcomes of all patients having ultrasoundguided foam sclerotherapy for varicose veins (see section 3.1). 1.3 The procedure should only be undertaken using sclerosants licensed for varicose veins. The practice of mixing liquid sclerosant with air or other gas constitutes off-label use. 1.4 Current evidence of long-term efficacy is limited and clinicians are encouraged to collect longer-term follow-up data. Endovenous laser treatment of the long saphenous vein. NICE interventional procedure guidance 52 (2004). 1.1 Current evidence on the safety and efficacy of endovenous laser treatment of the long saphenous vein appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance. Current evidence on the efficacy of this procedure is limited to case series with up to 3 years follow-up. Clinicians are encouraged to collect longer-term follow up data. Transilluminated powered phlebectomy for varicose veins. NICE interventional procedure guidance 37 (2004). 1.1 Current evidence on the safety and efficacy of transilluminated powered phlebectomy for varicose veins includes small numbers of patients and is of limited quality. It does not appear adequate to support the use of this procedure without special arrangements for consent and for audit or research. Clinicians wishing to undertake transilluminated powered phlebectomy for varicose veins should inform the clinical governance leads in their Trusts. They should ensure that patients offered it understand the uncertainty about the Page 12 of 16

13 procedure s safety and efficacy and should provide them with clear written information. Use of the Institute s Information for the Public is recommended. Clinicians should ensure that appropriate arrangements are in place for audit or research. Publication of safety and efficacy outcomes will be useful in reducing the current uncertainty. NICE is not undertaking further investigation at present. Radiofrequency ablation of varicose veins. NICE interventional procedure guidance 8 (2003). 1.1 Current evidence on the safety and efficacy of radiofrequency ablation of varicose veins appears adequate to support the use of this procedure as an alternative to saphenofemoral ligation and stripping, provided that the normal arrangements are in place for consent, audit and clinical governance. Page 13 of 16

14 Appendix C: Literature search for endovenous mechanochemical ablation for varicose veins Databases Cochrane Database of Systematic Reviews CDSR (Cochrane Library) Date searched Version/files 25/09/12 Issue 9 of 12, Sept 2012 Database of Abstracts of Reviews of 25/09/12 - Effects DARE (CRD website) HTA database (CRD website) 25/09/12 - Cochrane Central Database of Controlled Trials CENTRAL (Cochrane Library) 25/09/12 Issue 9 of 12, Sept 2012 MEDLINE (Ovid) 25/09/ to September Week MEDLINE In-Process (Ovid) 25/09/12 September 24, 2012 EMBASE (Ovid) 25/09/ to 2012 Week 38 CINAHL (NLH Search 2.0 or EBSCOhost) 25/09/12 - Trial sources searched: Current Controlled Trials metaregister of Controlled Trials mrct Clinicaltrials.gov National Institute for Health Research Clinical Research Network Coordinating Centre (NIHR CRN CC) Portfolio Database Websites searched: National Institute for Health and Clinical Excellence (NICE) Food and Drug Administration (FDA) MAUDE database French Health Authority (FHA) Australian Safety and Efficacy Register of New Interventional Procedures Surgical (ASERNIP S) Australia and New Zealand Horizon Scanning Network (ANZHSN) Conference search General internet search The following search strategy was used to identify papers in MEDLINE. A similar strategy was used to identify papers in other databases. 1 exp Venous Insufficiency/ 2 ((venous or vein*) adj3 (incomp* or insuffic*)).tw. Page 14 of 16

15 3 ((venous or vein*) adj3 ulcer*).tw. 4 telangiectasis/ 5 telangiect*.tw. 6 ((reticular or thread or spider) adj3 (vein* or venous)).tw. 7 or/1-6 8 exp lower extremity/ 9 (lower limb* or lower extremit* or leg* or calf or valves or thigh* or membrum inferius).tw. 10 or/ and exp varicose veins/ 13 (varicos* adj3 vein*).tw. 14 (varix or varices or microvaricosity or phlebarteriectasia or phlebectas* or prevaricos* or vein ectasia or venectasia).tw. 15 Saphenous Vein/ 16 ((saphenous or perforator) adj3 (vein* or vena or incomp* or insuffic*)).tw. 17 GSV.tw. 18 or/ clarivein.tw. 20 MOCA.tw. 21 ((mechanochemical or mechano-chemical or mechanical) adj3 ablat*).tw. 22 ((non-thermal or nonthermal or "non thermal") adj3 ablat*).tw. 23 (infus* adj3 catheter*).tw. 24 ((damag* or disrupt* or disturb* or destroy* or break* or destruct*) adj3 (endothelium or endothelial or lining)).tw. 25 (rotat* adj3 (wire* or tip*)).tw. 26 tumescentless.tw. 27 ((spasm* adj2 vein*) or venospasm).tw. Page 15 of 16

16 28 or/ and animals/ not humans/ not 30 Page 16 of 16