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Ann Phlebology 2024; 22(1): 36-38

Published online June 30, 2024

https://doi.org/10.37923/phle.2024.22.1.36

© Annals of phlebology

My Experience and Comprehension of Flebogrif®, a New Modality of Mechanochemical Ablation for Incompetent Saphenous Veins – What’s Different from ClariVein®?

Insoo Park, M.D., Sujin Park, M.D.

Charm Vascular Clinic, Seoul, Korea

Correspondence to : Insoo Park
Charm Vascular Clinic
Tel: 82-6959-1550
Fax: 82-6959-1551
E-mail: prs3131@naver.com

Received: April 8, 2024; Revised: May 21, 2024; Accepted: May 22, 2024

Flebogrif® is a new modality of mechanochemical ablation for incompetent saphenous vein treatment. With our experiences, it offers advantages such as reduced sclerosant dosage, shorter procedure times, lower catheter costs and in terms of closure rate as well. However, the potential for increased pain and thrombophlebitis due to more potent mechanical injury is apparent.

Keywords Chronic venous disease, Mechanochemical ablation, Clarivein, Flebogrif

The treatment modalities for chronic venous disease (CVD) have undergone significant evolution over the past decade. High ligation and stripping (HL/S), which removes the veins surgically, have evolved into endovenous thermal ablation (EVTA) technique like endovenous laser ablation (EVLA) and radiofrequency ablation (RFA), and non-thermal non-tumescent ablation (NTNT) technique represented by cyanoacrylate closure (CAC) and mechanochemical ablation (MOCA). Especially, NTNT technique has shown a steep increase in popularity in recent years, with efficient results being reported [1,2].

Two kinds of MOCA techniques, ClariVein® (Merit Medical, Utah, USA) and Flebogrif® (Balton, Warsaw, Poland), were approved and registered in Korea in June 2018 and February 2023, respectively by the Korea Food and Drug Administration (KFDA) and the Health Insurance Review and Assessment Service (HIRA). While both techniques are encompassed within the category of MOCA, ClariVein® has been relatively well-known and widespread compared to Flebogrif®, which emerged as a later entrant and is still relatively less common.

We have performed treatments using Flebogrif® since February 2023, treating over 250 patients with it. Flebogrif® has similar features to ClariVein® but also notable differences. As Flebogrif® is not yet FDA-approved, there is a lack of clinical research results in North America, but some studies have been published in European countries [3,4]. While not extensively used in Korea yet, as of March 2024, approximately 850 patients have been treated with Flebogrif®, with various centers accumulating initial experiences sporadically.

We hope to share experiences and insights regarding the characteristics, advantages, disadvantages, and helpful experiences for early users of Flebogrif®, comparing it with our extensive experience with ClariVein® of over 900 cases.

Similar to other endovenous modalities, ablation typically starts 2 cm distal to the saphenofemoral junction (SFJ). ClariVein® positions its outer catheter tip, through which the sclerosant injects, approximately 1–2 cm distal to the inner wire tip that causes mechanical injury. In contrast, Flebogrif® positions the tip for sclerosant injection approximately 1–2 cm proximal to the ‘cutting element’ that causes mechanical injury. Thus, during the procedure, careful attention should be paid to differentiate the positions of the tip and cutting element using ultrasound to prevent overly direct injection of sclerosant into the deep vein.

The cutting element designed to be exceptionally sharp, resulting in a more potent mechanical injury to the vein wall compared to ClariVein®. Consequently, if the procedure is conducted with the patient conscious, there may be a some level of pain induced during the pullback process in comparison to ClariVein®. Therefore, in cases where local anesthesia is administered, both the practitioner and the patient should take this into consideration.

ClariVein® utilizes pure liquid sclerosant, whereas Flebogrif® utilizes foam sclerosant, resulting in a reduction of the actual amount of pure liquid sclerosant by approximately one-fifth compared to ClariVein® due to the exclusion of air. Consequently, we suggest that the risk of chemical toxicity is reduced due to the lesser amount of sclerosant. As a matter of fact, we encountered a significant increase in blood creatine levels in two out of 900 patients during the ClariVein® procedure. Following the Instructions for Use (IFU), ClariVein® can treat up to 50 cm length of vein, if using liquid sclerosant up to 10 cc. Therefore, there may be limitations in treating two or more saphenous veins, but Flebogrif® may be relatively safer from such restrictions due to the lower amount of sclerosant. However, this may lead to an increase in the amount of injected air, and we opts for carbon dioxide instead of room air. There are some reports suggesting that faster dissolution of foam sclerosant with carbon dioxide reduces the risk of air embolism and side effects [5,6]. In a chart review of our datas, we analyzed that an average of approximately 15.85±5.71 cc of foam sclerosant was used during Flebogrif®, and no adverse events related to air embolism were experienced.

When the vein diameter is small (around 3–4 mm), there is a tendency for the catheter to be pushed distally as cutting element encounters resistance due to the small vein diameter during the process of releasing and stretching out the cutting element. Therefore, it is recommended to reassess and adjust the position using ultrasound after releasing the cutting element when treating small vein. Additionally, when releasing or unreleasing the cutting element, it is advised to perform the procedure with the catheter in as straight a state as possible, as curving the catheter can cause unnecessary resistance inside the catheter.

When treating one saphenous vein after another, saline flushing is recommended to wash out the clots in catheter. This is because clot formation within the catheter can lead to resistance during the process of releasing the cutting element or, rarely, may prevent interrupting altogether. There are two side holes for saline flushing thorough the catheter.

During catheter pullback, the operator may feel a sensation of the cutting element scratching the vein wall, with the intensity of the scratching sensation varying somewhat between procedures. In some cases, the scratching sensation may be strong, while in others, it may be very weak. From the author’s experience, it is considered that a stronger scratching sensation indicates a more powerful mechanical injury and may induce stronger spasm. However, we are unaware of the variables causing differences in the intensity of scratching sensation between procedures. Furthermore, we have not confirmed how such differences ultimately affect closure rates. If the scratching sensation is felt weakly, it is recommended to use ultrasound to ensure an adequate spasm before foam injection. If satisfactory spasm is not observed, additional scratching is advised before foam injection.

According to the Instructions for Use (IFU), additional mechanical injury could be considered, especially if the vein diameter exceeds 12 mm [7]. During our early experience period to ensure a stable closure rate, we performed mechanical injury twice for every veins, then reduced to once after gaining some experience, especially if the diameter is not large (e.g., less than 5 mm). However, if the diameter is deemed not small (e.g., 5–6 mm or larger), we perform mechanical injury twice. Despite being anecdotal, we have experienced a case of recanalization one month after performing four times mechanical injury in a patient with a diameter of approximately 15 mm. As with all endovenous modalities, closure rate in large diameter cases are inevitably a concern, according to our opinion.

One significant advantage of the procedure is the greatly reduced treatment time compared to ClariVein®. In the case of ClariVein®, the typical pull-back speed of the catheter is about 5–10 seconds per centimeter [8]. However, with Flebogrif®, it takes about 3–4 seconds per 10 centimeters. Therefore, assuming a treatment length of approximately 40 centimeters of the GSV, ClariVein® would take about 200–400 seconds, while Flebogrif® would take approximately 10–15 seconds.

We have never encountered deep vein thrombosis (DVT) in any cases thus far. During the several seconds of catheter pull-back with sclerosant injection, an assistant compresses the deep vein junction with the sonogram probe. The purpose of this is to minimize the direct influx of foam sclerosant into the deep vein. It remains uncertain whether this technique contributes to preventing DVT. Notably, treatments are conducted in the supine position without the use of Trendelenburg or reverse Trendelenburg positions.

Thrombophlebitis is estimated to occur in approximately 10% of patients post-procedure, a figure consistent with existing literature [9]. However, compared to ClariVein®, there appears to be a slightly higher tendency for associated pain when thrombophlebitis occurs. Although the exact cause is unknown, we speculate that the more severe injury to the vein wall may lead to a more pronounced inflammatory reaction compared to ClariVein®.

Medical compression stockings are recommended for two weeks post-procedure, similar to conventional other treatment modalities.

In terms of closure rate, the previous literature demonstrates excellent outcomes. We have also experienced good results of over 95% in six months follow-up duplex after procedure. However, there seems to be a tendency for closure rate to decrease slightly in cases of larger diameter veins (e.g., 1 cm or more), which will be reported through our systematic studies in the future. Some studies have reported that the closure rate of ClariVein® is inferior to other endovenous modalities [3]. Given that Flebogrif® induces stronger mechanical injury than ClariVein®, we believe there may be superior advantages in terms of closure rate.

During the follow-up period, rapid fibrotic changes in the treated vein are observed. From our experience, ClariVein® typically shows ultrasound-detected fibrotic changes progressing to the point of treated vein loss around six months post-procedure. We have observed that Flebogrif® induces similar or even faster fibrotic changes. This is believed to be due to more potent mechanical injury, leading to faster inflammatory fibrotic changes.

In summary, Flebogrif® offers advantages such as reduced sclerosant dosage, shorter procedure times, and lower catheter costs. While exact costs can vary, in Korea, Flebogrif® is typically about 200–300 USD cheaper than ClariVein®. Although more research results are needed, in our opinion, there appear to be advantages in terms of closure rate as well. However, the potential for increased pain and thrombophlebitis due to more potent mechanical injury is apparent. Therefore, it is anticipated that comprehensive systematic research results from various countries and institutions will shed more light on this in the future.

  1. Bontinis V, Bontinis A, Koutsoumpelis A, Chorti A, Rafailidis V, Giannopoulos A, et al. A network meta-analysis on the efficacy and safety of thermal and nonthermal endovenous ablation treatments. J Vasc Surg Venous Lymph Disord. 2023;11:854-65.e5.
  2. Shahzad N, Elsherif M, Obaidat I, Brar R. A systematic review and meta-analysis of randomised controlled trials comparing thermal versus non-thermal endovenous ablation in superficial venous incompetence. Eur J Vasc Endovasc Surg. 2023;66:687-95.
  3. Lim AJM, Mohamed AH, Hitchman LH, Lathan R, Ravindhran B, Sidapra MM, et al. Clinical outcomes following mechanochemical ablation of superficial venous incompetence compared with endothermal ablation: meta-analysis. Br J Surg. 2023;110:562-7.
  4. Ammollo RP, Petrone A, Giribono AM, Ferrante L, del Guercio L, Bracale UM. Early Results of mechanochemical ablation with Flebogrif® in great saphenous vein Insufficiency: does Polidocanol Concentration Affect Outcome? Transl Med UniSA. 2020;21:47-51.
  5. Morrison N, Neuhardt DL, Rogers CR, McEown J, Morrison T, Johnson E, et al. Comparisons of side effects using air and carbon dioxide foam for endovenous chemical ablation. J of Vasc Surg. 2008;47:830-6.
  6. Wong M. Should foam made with physiologic gases be the standard in sclerotherapy? Phlebology. 2015;30:580-6.
  7. INSTRUCTIONS FOR USE, Set for venous insufficiency treatment, FLEBOGRIF. BALTON. https://balton.pl/en/instrukcja-uzycia/Flebogrif%20MDF_FLE_A-.1_IFU[2]_EN_ppcayUbMVX5zdCZYemtN.
  8. lozai T, Huizing E, Schreve M, Mooij MC, van Vlijmen CJ, Wisselink W, et al. A systematic review and meta-analysis of mechanochemical endovenous ablation using Flebogrif for varicose veins. J Vasc Surg Venous Lymph Disord. 2022;10:248-57.e2.

Brief communication

Ann Phlebology 2024; 22(1): 36-38

Published online June 30, 2024 https://doi.org/10.37923/phle.2024.22.1.36

Copyright © Annals of phlebology.

My Experience and Comprehension of Flebogrif®, a New Modality of Mechanochemical Ablation for Incompetent Saphenous Veins – What’s Different from ClariVein®?

Insoo Park, M.D., Sujin Park, M.D.

Charm Vascular Clinic, Seoul, Korea

Correspondence to:Insoo Park
Charm Vascular Clinic
Tel: 82-6959-1550
Fax: 82-6959-1551
E-mail: prs3131@naver.com

Received: April 8, 2024; Revised: May 21, 2024; Accepted: May 22, 2024

Abstract

Flebogrif® is a new modality of mechanochemical ablation for incompetent saphenous vein treatment. With our experiences, it offers advantages such as reduced sclerosant dosage, shorter procedure times, lower catheter costs and in terms of closure rate as well. However, the potential for increased pain and thrombophlebitis due to more potent mechanical injury is apparent.

Keywords: Chronic venous disease, Mechanochemical ablation, Clarivein, Flebogrif

Introduction

The treatment modalities for chronic venous disease (CVD) have undergone significant evolution over the past decade. High ligation and stripping (HL/S), which removes the veins surgically, have evolved into endovenous thermal ablation (EVTA) technique like endovenous laser ablation (EVLA) and radiofrequency ablation (RFA), and non-thermal non-tumescent ablation (NTNT) technique represented by cyanoacrylate closure (CAC) and mechanochemical ablation (MOCA). Especially, NTNT technique has shown a steep increase in popularity in recent years, with efficient results being reported [1,2].

Two kinds of MOCA techniques, ClariVein® (Merit Medical, Utah, USA) and Flebogrif® (Balton, Warsaw, Poland), were approved and registered in Korea in June 2018 and February 2023, respectively by the Korea Food and Drug Administration (KFDA) and the Health Insurance Review and Assessment Service (HIRA). While both techniques are encompassed within the category of MOCA, ClariVein® has been relatively well-known and widespread compared to Flebogrif®, which emerged as a later entrant and is still relatively less common.

We have performed treatments using Flebogrif® since February 2023, treating over 250 patients with it. Flebogrif® has similar features to ClariVein® but also notable differences. As Flebogrif® is not yet FDA-approved, there is a lack of clinical research results in North America, but some studies have been published in European countries [3,4]. While not extensively used in Korea yet, as of March 2024, approximately 850 patients have been treated with Flebogrif®, with various centers accumulating initial experiences sporadically.

We hope to share experiences and insights regarding the characteristics, advantages, disadvantages, and helpful experiences for early users of Flebogrif®, comparing it with our extensive experience with ClariVein® of over 900 cases.

Experiences and considerations during the procedure

Similar to other endovenous modalities, ablation typically starts 2 cm distal to the saphenofemoral junction (SFJ). ClariVein® positions its outer catheter tip, through which the sclerosant injects, approximately 1–2 cm distal to the inner wire tip that causes mechanical injury. In contrast, Flebogrif® positions the tip for sclerosant injection approximately 1–2 cm proximal to the ‘cutting element’ that causes mechanical injury. Thus, during the procedure, careful attention should be paid to differentiate the positions of the tip and cutting element using ultrasound to prevent overly direct injection of sclerosant into the deep vein.

The cutting element designed to be exceptionally sharp, resulting in a more potent mechanical injury to the vein wall compared to ClariVein®. Consequently, if the procedure is conducted with the patient conscious, there may be a some level of pain induced during the pullback process in comparison to ClariVein®. Therefore, in cases where local anesthesia is administered, both the practitioner and the patient should take this into consideration.

ClariVein® utilizes pure liquid sclerosant, whereas Flebogrif® utilizes foam sclerosant, resulting in a reduction of the actual amount of pure liquid sclerosant by approximately one-fifth compared to ClariVein® due to the exclusion of air. Consequently, we suggest that the risk of chemical toxicity is reduced due to the lesser amount of sclerosant. As a matter of fact, we encountered a significant increase in blood creatine levels in two out of 900 patients during the ClariVein® procedure. Following the Instructions for Use (IFU), ClariVein® can treat up to 50 cm length of vein, if using liquid sclerosant up to 10 cc. Therefore, there may be limitations in treating two or more saphenous veins, but Flebogrif® may be relatively safer from such restrictions due to the lower amount of sclerosant. However, this may lead to an increase in the amount of injected air, and we opts for carbon dioxide instead of room air. There are some reports suggesting that faster dissolution of foam sclerosant with carbon dioxide reduces the risk of air embolism and side effects [5,6]. In a chart review of our datas, we analyzed that an average of approximately 15.85±5.71 cc of foam sclerosant was used during Flebogrif®, and no adverse events related to air embolism were experienced.

When the vein diameter is small (around 3–4 mm), there is a tendency for the catheter to be pushed distally as cutting element encounters resistance due to the small vein diameter during the process of releasing and stretching out the cutting element. Therefore, it is recommended to reassess and adjust the position using ultrasound after releasing the cutting element when treating small vein. Additionally, when releasing or unreleasing the cutting element, it is advised to perform the procedure with the catheter in as straight a state as possible, as curving the catheter can cause unnecessary resistance inside the catheter.

When treating one saphenous vein after another, saline flushing is recommended to wash out the clots in catheter. This is because clot formation within the catheter can lead to resistance during the process of releasing the cutting element or, rarely, may prevent interrupting altogether. There are two side holes for saline flushing thorough the catheter.

During catheter pullback, the operator may feel a sensation of the cutting element scratching the vein wall, with the intensity of the scratching sensation varying somewhat between procedures. In some cases, the scratching sensation may be strong, while in others, it may be very weak. From the author’s experience, it is considered that a stronger scratching sensation indicates a more powerful mechanical injury and may induce stronger spasm. However, we are unaware of the variables causing differences in the intensity of scratching sensation between procedures. Furthermore, we have not confirmed how such differences ultimately affect closure rates. If the scratching sensation is felt weakly, it is recommended to use ultrasound to ensure an adequate spasm before foam injection. If satisfactory spasm is not observed, additional scratching is advised before foam injection.

According to the Instructions for Use (IFU), additional mechanical injury could be considered, especially if the vein diameter exceeds 12 mm [7]. During our early experience period to ensure a stable closure rate, we performed mechanical injury twice for every veins, then reduced to once after gaining some experience, especially if the diameter is not large (e.g., less than 5 mm). However, if the diameter is deemed not small (e.g., 5–6 mm or larger), we perform mechanical injury twice. Despite being anecdotal, we have experienced a case of recanalization one month after performing four times mechanical injury in a patient with a diameter of approximately 15 mm. As with all endovenous modalities, closure rate in large diameter cases are inevitably a concern, according to our opinion.

One significant advantage of the procedure is the greatly reduced treatment time compared to ClariVein®. In the case of ClariVein®, the typical pull-back speed of the catheter is about 5–10 seconds per centimeter [8]. However, with Flebogrif®, it takes about 3–4 seconds per 10 centimeters. Therefore, assuming a treatment length of approximately 40 centimeters of the GSV, ClariVein® would take about 200–400 seconds, while Flebogrif® would take approximately 10–15 seconds.

Experiences and considerations after procedure

We have never encountered deep vein thrombosis (DVT) in any cases thus far. During the several seconds of catheter pull-back with sclerosant injection, an assistant compresses the deep vein junction with the sonogram probe. The purpose of this is to minimize the direct influx of foam sclerosant into the deep vein. It remains uncertain whether this technique contributes to preventing DVT. Notably, treatments are conducted in the supine position without the use of Trendelenburg or reverse Trendelenburg positions.

Thrombophlebitis is estimated to occur in approximately 10% of patients post-procedure, a figure consistent with existing literature [9]. However, compared to ClariVein®, there appears to be a slightly higher tendency for associated pain when thrombophlebitis occurs. Although the exact cause is unknown, we speculate that the more severe injury to the vein wall may lead to a more pronounced inflammatory reaction compared to ClariVein®.

Medical compression stockings are recommended for two weeks post-procedure, similar to conventional other treatment modalities.

In terms of closure rate, the previous literature demonstrates excellent outcomes. We have also experienced good results of over 95% in six months follow-up duplex after procedure. However, there seems to be a tendency for closure rate to decrease slightly in cases of larger diameter veins (e.g., 1 cm or more), which will be reported through our systematic studies in the future. Some studies have reported that the closure rate of ClariVein® is inferior to other endovenous modalities [3]. Given that Flebogrif® induces stronger mechanical injury than ClariVein®, we believe there may be superior advantages in terms of closure rate.

During the follow-up period, rapid fibrotic changes in the treated vein are observed. From our experience, ClariVein® typically shows ultrasound-detected fibrotic changes progressing to the point of treated vein loss around six months post-procedure. We have observed that Flebogrif® induces similar or even faster fibrotic changes. This is believed to be due to more potent mechanical injury, leading to faster inflammatory fibrotic changes.

In summary, Flebogrif® offers advantages such as reduced sclerosant dosage, shorter procedure times, and lower catheter costs. While exact costs can vary, in Korea, Flebogrif® is typically about 200–300 USD cheaper than ClariVein®. Although more research results are needed, in our opinion, there appear to be advantages in terms of closure rate as well. However, the potential for increased pain and thrombophlebitis due to more potent mechanical injury is apparent. Therefore, it is anticipated that comprehensive systematic research results from various countries and institutions will shed more light on this in the future.

Conflicts of interest

The authors declare no conflicts of interest.

References

  1. Bontinis V, Bontinis A, Koutsoumpelis A, Chorti A, Rafailidis V, Giannopoulos A, et al. A network meta-analysis on the efficacy and safety of thermal and nonthermal endovenous ablation treatments. J Vasc Surg Venous Lymph Disord. 2023;11:854-65.e5.
  2. Shahzad N, Elsherif M, Obaidat I, Brar R. A systematic review and meta-analysis of randomised controlled trials comparing thermal versus non-thermal endovenous ablation in superficial venous incompetence. Eur J Vasc Endovasc Surg. 2023;66:687-95.
  3. Lim AJM, Mohamed AH, Hitchman LH, Lathan R, Ravindhran B, Sidapra MM, et al. Clinical outcomes following mechanochemical ablation of superficial venous incompetence compared with endothermal ablation: meta-analysis. Br J Surg. 2023;110:562-7.
  4. Ammollo RP, Petrone A, Giribono AM, Ferrante L, del Guercio L, Bracale UM. Early Results of mechanochemical ablation with Flebogrif® in great saphenous vein Insufficiency: does Polidocanol Concentration Affect Outcome? Transl Med UniSA. 2020;21:47-51.
  5. Morrison N, Neuhardt DL, Rogers CR, McEown J, Morrison T, Johnson E, et al. Comparisons of side effects using air and carbon dioxide foam for endovenous chemical ablation. J of Vasc Surg. 2008;47:830-6.
  6. Wong M. Should foam made with physiologic gases be the standard in sclerotherapy? Phlebology. 2015;30:580-6.
  7. INSTRUCTIONS FOR USE, Set for venous insufficiency treatment, FLEBOGRIF. BALTON. https://balton.pl/en/instrukcja-uzycia/Flebogrif%20MDF_FLE_A-.1_IFU[2]_EN_ppcayUbMVX5zdCZYemtN.
  8. INSTRUCTIONS FOR USE, ClariVein. https://clarivein.com/wp-content/uploads/2015/07/IFU-001-Instruction-for-Use-IC-REV-B.pdf.
  9. lozai T, Huizing E, Schreve M, Mooij MC, van Vlijmen CJ, Wisselink W, et al. A systematic review and meta-analysis of mechanochemical endovenous ablation using Flebogrif for varicose veins. J Vasc Surg Venous Lymph Disord. 2022;10:248-57.e2.
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Vol.22 No.1 Jun 30, 2024, pp. 1~8

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