Treatment for chronic venous disorders (CVD) has evolved rapidly since entering the 2000s, especially with the introduction of endovenous thermal ablation (ETA). Shortly after ETA became established, non-thermal, non-tumescent ablation (NTNT) techniques emerged, and over the past decade, accumulating studies have increasingly affirmed their efficacy [1,2]. Among NTNT methods, mechanochemical ablation (MOCA) is represented primarily by two modalities: the well-known ClariVein^® and the relatively newer Flebogrif^® [3]. Flebogrif^® has not yet been approved by the FDA, resulting in limited research, while ClariVein^®, a U.S.-manufactured device, has been the subject of numerous studies. Both techniques have shown favorable outcomes, although some research suggests that ClariVein^®’s closure rates are lower than those achieved with ETA [4].

According to some studies, Flebogrif^® reports a closure rate of over 90%, comparable to ETA [5-8]. However, more large-scale, prospective studies and long-term data are needed to confirm.

In South Korea, the KFDA approved ClariVein^® in 2018 and Flebogrif^® in 2023. Flebogrif^® is exclusively approved in South Korea within Asia. This study is a retrospective analysis of the early outcomes of Flebogrif^® at a single institution and represents the first published clinical results in Asia.

1. Patients and study design

This retrospective study included patients treated with Flebogrif^® (Balton, Warsaw, Poland) between May and Jun 2023 at Charm Vascular Clinic in Seoul, South Korea. Procedures were performed by two experienced vascular surgeons, each with thousands of cases of endovenous treatment and duplex ultrasound expertise. All patients provided written informed consent.

2. Eligibility criteria

• Age: 18–80 years

• Unilateral or bilateral symptomatic limbs (aching, cramping, heaviness, tingling, edema)

• Primary great saphenous vein (GSV) or small saphenous vein (SSV) incompetence

• Saphenous vein diameter >3 mm at 5 cm from the deep vein junction

• Pathologic reflux >0.5 seconds in a standing position

3. Exclusion criteria

• Pregnancy or lactation

• Superficial thrombophlebitis

• History of deep vein thrombosis (DVT)

• Coagulation disorders or increased thromboembolism risk

• Use of direct oral anticoagulants or vitamin K antagonists

• Immobilization

• Severe renal or liver insufficiency

• Peripheral arterial disease

The study included 55 patients with 113 incompetent saphenous veins. Preoperative clinical, etiologic, anatomic, and pathophysiologic (CEAP) classification was defined as follows: C1 (telangiectasia or reticular veins), C2 (varix), C3 (edema), C4 (pigmentation, eczema, lipodermatosclerosis, atrophie blanche, or corona phlebectatica), and C5 (healed ulcer). The diameter of each vein was measured 5 cm below the deep vein junction, avoiding aneurysmal changes area. Preoperative scores included the revised venous clinical severity (rVCSS) and the Chronic Venous Insufficiency Quality of Life Questionnaire (CIVIQ-14).

4. Primary outcome

The primary outcome was treatment success, defined by anatomical success in the treated vein segment, as assessed by duplex ultrasound at 1 and 3 months post-procedure.

• Anatomical success: complete occlusion or a recanalized segment <3 cm

• Anatomical failure: partial recanalization (>3 cm) or complete recanalization of the entire treated vein

5. Secondary outcomes

Secondary outcomes included postprocedural complications (infection, ecchymosis, hyperpigmentation, thrombophlebitis, paresthesia, and deep vein thrombosis), foam sclerosing agent dose, and days to return to normal activities. Postoperative pain was assessed using the numerical pain rating scale (NRS, 0–10) at 6 hours, 1 day, 10 days, and 1 month post-procedure.

6. Procedure

On the day of the procedure, vein locations were marked with ultrasound guidance (P7, GE Healthcare) while the patient was standing. Procedures were performed under local anesthesia with IV sedation (propofol or midazolam or dexmedetomidine) administered under anesthesiologist supervision. Treatments were conducted in a supine position, with aseptic preparation of the full leg range.

Using ultrasound guidance, a 16G needle punctured the vein, and the Flebogrif^® kit’s guidewire and sheath (0.035-inch guidewire, 6Fr sheath) were used in an over-the-wire (OTW) technique. Treatment began approximately 2 cm below the saphenofemoral junction (SFJ) or saphenopopliteal junction (SPJ). All treatments for the saphenous vein were performed from the starting point of reflux to its endpoint. If reflux extended to the ankle, treatment was ended just above the ankle.

The Flebogrif^® catheter, equipped with five cutting elements, provided mechanical injury while injecting foam sclerosant (2% Sodium Tetradecyl Sulfate, STS) for chemical injury.

Following the manufacturer’s instructions, foam sclerosant was injected at 0.2 cc per cm [9]. The foam was prepared by mixing 1 cc of 2% STS with 4 cc of CO₂ gas using the Tessari method. Most veins received two-rounds of mechanical injury, with preliminary mechanical injury. Depending, smaller veins undergo only one-round mechanical injury without preliminary injury. The catheter pull-back speed was approximately 10 cm over 2–3 seconds, with simultaneous pull-back and foam injection. During foam sclerosant injection, the SFJ and SPJ were continuously compressed using a probe.

When treating more than one saphenous vein, the same method was applied to each additional saphenous vein, followed by concomitant phlebectomy or sclerotherapy if necessary. Compression stockings (20–30 mmHg) were recommended for 2 weeks post-procedure, with immediate return to light activities.

Table 1 shows the characteristics of the patients and veins that were treated. As mentioned earlier, an average of 2.05±0.70 mechanical injuries per vein were performed as preliminary mechanical injury. Multiple saphenous veins were treated without restrictions, and foam sclerosant volume varied depending on the total vein length, ranging from as little as 7 cc to as much as 28 cc.

Table 1 . Baseline patient and treated vein characteristics.

Variables	Mean±SD (range) or No. (%)
No. of patients	55
Mean age (years)	49.8±12.5 (24–71)
No. of female	42 (76.4)
Mean BMI (kg/m2)	24.1±4.1 (17.4–38.7)
CEAP
C1	7
C2	29
C3	12
C4	6
C5	1
No. of treated veins
GSV	94
SSV	19
Mean diameter (cm)
Total	0.53±0.18 (0.30–1.34)
GSV	0.51±0.17 (0.30–1.14)
SSV	0.61±0.21 (0.35–1.34)
No. of mechanical injury per vein	1.87±0.67 (1–4)
GSV	1.96±0.67 (1–4)
SSV	1.45±0.51 (1–2)
No. of treated saphenous vein per patient	2.05±0.70 (1–4)
Total dose of foam (cc) per patient	15.85±5.71 (7.0–28.0)
Concomitant procedure (%)
Miniphlebectomy	83.6%
Sclerotherapy	90.9%
Initial rTCSS	4.3±1.8 (2–10)
Initial CIVIQ14	27.0±5.1 (18–37)

Adverse events observed post-procedure are listed in Table 2. Thrombophlebitis was defined as pain, redness, heatness or swelling along the treated saphenous vein, with the patient requiring oral medication or undergoing thrombus or coagulum removal. Cases where only observation was needed with mild symptoms were excluded. All adverse events were mild. And there were no severe adverse events such as paresthesia or DVT.

Table 2 . Adverse events after procedure.

	N (%)
Infection	0 (0)
Ecchymosis	1 (0.8)
Hyperpigmentation	4 (3.5)
Thrombophlebitis	4 (3.5)
Paresthesia	0 (0)
DVT	0 (0)

The post-procedural pain scores using NRS at 6 hours, 1 day, 10 days, and 1 month were 0.33±0.73 (0–3), 0.20±0.45 (0–2), 0.30±0.79 (0–4), and 0.11±0.32 (0–1), respectively. The mean time to return to normal activity was 1.07±0.42 (0–3) days.

The anatomical closure rate is summarized in Table 3. The average follow-up period for the 1-month group was 34.8±6.7 (28–55) days, and for the 3-month group, it was 119.1±24.1 (81–172) days. The follow-up rate was 99.1% at 1 month and 57.5% at 3 months. In the case of SSV, the closure rate at 3 months appears to have increased, but this is likely due to the small sample size and a significant number of losses, which affected the analysis.

Table 3 . Anatomical success rate after procedure.

	1 month	3 months
Total	97.3% (109/112)	96.9% (63/65)
GSV (n=94)	100% (93/93)	98.1% (52/53)
SSV (n=19)	84.2% (16/19)	91.7% (11/12)

The revised Venous Clinical Severity Score (rVCSS) at 1 month and 3 months was 1.17±0.77 (0–3) and 1.07±0.83 (0–2), respectively. The CIVIQ-14 scores at 1 month and 3 months were 17.76±2.18 (14–24) and 17.63±2.34 (15–22), respectively. Both scores showed a statistically significant decrease from the initial scores.

Flebogrif^® is the latest modality among existing NTNT and has relatively fewer research results compared to other NTNT techniques. Although it has a similar mechanism to ClariVein^®, which is also a type of MOCA, there are significant differences.

1. The cutting element responsible for the mechanical injury in Flebogrif^® is much sharper and more precise compared to ClariVein^®’s.

2. Foam mixed with air is applied, which reduces the actual amount of chemical sclerosant to about 20%.

3. The procedure relies on manual injury rather than motor-driven electrical injury.

4. The pull-back speed is dozens of times faster than that of ClariVein^®.

5. The OTW technique can be applied.

In existing literature on Flebogrif^®, detailed information on the dosage of foam sclerosant is limited. According to Zubilewicz’s [10] study, an average amount 6.5 cc was used when treating a single saphenous vein, and his another study reports a similar amount of 8.69±2.23 cc for a single saphenous vein treatment [11]. In this study, the authors treated an average of 2.05 veins without restricting the number of saphenous veins, resulting in an average sclerosant volume exceeding 15.85±5.71 cc.

The instructions for use for ClariVein recommends using liquid sclerosant in amounts below 10 cc [12]. In contrast, Flebogrif uses foam sclerosant mixed with air, reducing the actual liquid sclerosant volume to approximately 20%. In this study, while the average amount of foam used was 15.85 cc, the actual liquid sclerosant volume could be estimated at around 3 cc. Thus, compared to ClariVein, it is possible to use less sclerosant.

Although there are few systematic studies on the dose limitation of foam sclerosant, a recommended limit of 10–20 cc exists [2,13,14]. However, in this study, the authors’ average dose exceeded 15 cc, with a maximum of 28 cc. Since this study, Flebogrif has been applied in hundreds of patients in our clinic, consistently using an average foam sclerosant volume above 15 cc, without adverse events such as DVT, toxicity or embolism. The authors use CO₂ instead of room air, although it is unclear if this contributes to preventing additional adverse events. The authors believe further research is needed on the dose limitation of foam sclerosant, and await research outcomes from other centers treating multiple saphenous veins with Flebogrif.

The primary disadvantage of NTNT methods is the high cost. Thus, no studies have shown that NTNT methods are more cost-effective than ETA techniques. However, Flebogrif is the most affordable option among the NTNT methods, suggesting it may offer relatively better cost-effectiveness.

In conclusion, this study demonstrates safe and favorable early outcomes for CVD treatment with Flebogrif, comparable to ETA techniques, while using lower sclerosant doses and offering cost advantages over other MOCA techniques. We anticipate positive long-term efficacy results.

The authors declare no conflicts of interest.