Baseline characteristics

Demographic details

The main baseline characteristics of study participants are shown in Table 16. There was a good balance between groups for most factors, particularly for age and sex, which were minimisation variables. There was a slight imbalance between groups in terms of bilateral disease. The data shown in Table 16 were used in the analysis when adjusting for minimisation factors.

TABLE 16

Baseline characteristics of study participants: comparison of surgery against foam sclerotherapy

Quality of life

Quality of life was assessed prior to the patient being randomised. QoL appeared to be slightly better in the foam group and this is reflected in the AVVQ, EQ-5D and each of the SF-36 components and subdomain scores (Table 17). For foam, the baseline AVVQ score was 17.6 (SD 10.0) and for surgery it was 18.2 (SD 9.2) (higher scores indicate worse QoL).

TABLE 17

Quality of life at baseline: comparison of surgery against foam sclerotherapy

Physical activity

There was a good balance between the groups in terms of physical activity at baseline (Table 18).

TABLE 18

Physical activity at baseline: comparison of surgery against foam sclerotherapy

Varicose vein characteristics

Baseline characteristics describing the varicose veins in the participants’ study and contralateral legs are shown in Tables 19 and 20 respectively. The groups are well balanced across the majority of factors (except for deep-vein reflux, where 17% in the foam group were affected compared with 9% in the surgery group).

TABLE 19

Baseline characteristics of study leg: comparison of surgery against foam sclerotherapy

TABLE 20

Baseline characteristics of contralateral leg in patients who had bilateral varicose veins: comparison of surgery against foam sclerotherapy

Procedure and treatment time

At the time of the primary intervention, more participants in the surgery arm had treatment to non-truncal varicosities (90%) than in the foam arm (31%) (see Table 21). More patients in the surgery arm (15%) had their contralateral leg treated at the same time than in the foam arm (3%).

The mean treatment duration (the time taken from preparation of the patient to completion of bandaging) was longer for surgery (53 minutes, SD 22.9 minutes) than for foam (19 minutes, SD 10.6 minutes). Foam sclerotherapy was performed by consultants much more often (77% of treatments) than surgery (59%). Only 8% of foam participants received treatment from a trainee, compared with 32% in the surgery group. The remainder of procedures were performed by staff grades or nurse consultants. Nearly all patients (98%) randomised to surgery had a general anaesthetic, with six receiving an epidural/spinal anaesthetic (Table 22). The anaesthetist was a consultant in 83% of cases.

TABLE 22

Description of anaesthetic

Primary treatment volume of foam

The total mean volume of foam administered was 9.0 ml (SD 2.9 ml). When the GSV alone was treated, the mean volume was 9.2 ml (SD 2.9 ml), with 8 ml (SD 3.0 ml) to the truncal vein and 1.2 ml (SD 2.2 ml) to the truncal varicosities (Table 23). There were six patients who received foam in excess of the 12-ml limit recommended in the protocol, without adverse consequences.

TABLE 23

Volume of foam administered at primary treatment

Secondary or tertiary foam treatments

The numbers of participants who received secondary or tertiary treatments of foam sclerotherapy, along with a breakdown of the location of treatment, is shown in Table 24. Seventeen participants randomised to foam sclerotherapy (7%) received additional foam treatment to non-truncal varicosities, compared with one randomised to surgery (1%). There were two participants whose second foam treatment included foam sclerotherapy to the GSV and also to non-truncal varicosities. The one participant who received a tertiary treatment had treatment to both the SSV and GSV.

TABLE 24

Secondary foam treatment

Bandaging/compression

All participants had a bandage or stocking applied to their study leg, nearly all of which were full length. More foam participants (38%) than surgery participants (11%) received bandaging not according to protocol (see Table 21). The main reason for this difference was that the protocol specified the brand of bandaging/compression for patients undergoing foam sclerotherapy, whereas, for surgery, any type of bandaging for 10 days was sufficient. Of the 103 cases of foam participants whose bandaging was not according to protocol, only 10 were related to duration and the other 93 were related to the type of stockings.

Aberdeen Varicose Vein Questionnaire

At 6 weeks and 6 months, all QoL measures showed an apparent improvement compared with baseline. The treatment effect estimate for AVVQ (our primary outcome) at 6 weeks was −2.26 (95% CI −3.67 to −0.86, p = 0.002) in favour of surgery and at 6 months the estimate was −1.74 (95% CI −2.97 to −0.50, p = 0.006).

Sensitivity analyses

There were some missing AVVQ scores at 6 months (26% for the surgery arm and 17% for foam). Exploratory analysis shows that participants without a valid AVVQ score at 6 months had mean baseline AVVQ scores of 18.3 (SD 11.4) for foam and 18.2 (SD 10.3) for surgery. Those with an AVVQ score at 6 months had mean baseline scores of 17.4 (SD 9.7) for foam and 18.2 (SD 8.8) for surgery, indicating that there are differences in the missing data between groups. The mean AVVQ score at 6 weeks for participants with missing scores at 6 months is 11.8 for foam (slightly lower than the mean for all foam participants) and 7.7 for surgery (much lower than the mean for all surgery participants), which suggests that the treatment effect of −1.74 in favour of surgery may be underestimated in the primary analysis.

Table 28 demonstrates different estimates of the effect of treatment on the primary outcome when all missing AVVQ scores at 6 months have been imputed under varying assumptions. Under the ‘missing not at random’ assumption, the estimate of treatment effect is −2.00 (95% CI −3.30 to −0.70). Variously adding or subtracting two points to or from these imputed values, for either one arm at a time or both arms simultaneously, the resulting estimates range from −1.47 to −2.52, all significantly in favour of surgery. The missing AVVQ values for surgery would need to be at least 2.7 points higher (or the missing values for foam 4.0 points lower) than the imputed values for the difference between the groups to be non-significant.

TABLE 28

Sensitivity of estimates of the effect of treatment on the AVVQ score at 6 months (primary outcome) using other missing data assumptions: comparison of surgery with foam sclerotherapy

Short Form questionnaire-36 items

There were no differences between foam and surgery for the overall physical and mental component scores or individual domains of the SF-36.

European Quality of Life-5 Dimensions

There were no differences in the EQ-5D or EQ-5D VAS between the foam and surgery groups.

Clinical outcomes

Venous Clinical Severity Score and presence of residual varicose veins

These outcomes at 6 weeks and 6 months are presented in Tables 29 and 30 respectively, with the estimates of treatment effect sizes when surgery is compared with foam shown in Table 31.

TABLE 29

Clinical outcomes for study leg at 6 weeks: comparison of surgery with foam sclerotherapy

TABLE 30

Clinical outcomes for study leg at 6 months: comparison of surgery with foam sclerotherapy

TABLE 31

Estimates of the effect of treatment on clinical outcomes: comparison of surgery with foam sclerotherapy

Each outcome showed an apparent improvement in both groups from baseline to 6 weeks and from 6 weeks to 6 months. The VCSS was significantly lower for surgery than for foam after 6 weeks, with an effect size of −0.52 (95% CI −0.85 to −0.19, p = 0.002). However, there was no difference between groups at 6 months, when the effect size reduced (−0.23, 95% CI −0.53 to 0.07; p = 0.130).

Both the participant and nurse assessments (as assessed by the VAS) showed that there were fewer residual varicose veins for surgery than for foam at both follow-up time points [p < 0.001 (patient at 6 weeks –0.99, 95% CI –1.31 to –0.68, and at 6 months –0.95, 95% CI –1.27 to –0.63; nurse at 6 weeks –0.87, 95% CI –1.09 to –0.65, and at 6 months –0.50, 95% CI –0.71 to –0.30)].

The CEAP classification is presented for completeness, although it is generally accepted that this should not be used as a measure of treatment outcome.⁷² By 6 months, 75% of those in the surgery arm were classed as CEAP C0 or C1, compared with 64% of those in the foam sclerotherapy arm.

Ablation rates

These are shown in Tables 32 and 33 for 6 weeks and 6 months respectively. The overall statistical analyses for the whole leg and the GSV only are shown in Table 34. The number of participants undergoing treatment to the SSV alone or in combination with the GSV was small, and therefore these subgroups were not subjected to statistical analysis.

TABLE 32

Anatomical success at 6 weeks: comparison of surgery with foam sclerotherapy

TABLE 33

Anatomical success at 6 months: comparison of surgery with foam sclerotherapy

TABLE 34

Estimates of the effect of treatment on anatomical success: comparison of surgery with foam sclerotherapy

For the whole leg, the rate of successful ablation was significantly higher in the surgery group than in the foam sclerotherapy group at 6 weeks and 6 months (6 months OR 3.37, 95% CI 2.26 to 5.02; p < 0.001). Similar results were obtained for treatment to the GSV only at both time points (6 months OR 4.94, 95% CI 3.07 to 7.93; p < 0.001).

Procedural complications

The event rate for any complication was similar in both groups (6% for foam and 7% for surgery) (Table 35). Six participants in the foam group (2%) and three in the surgery group (1%) each experienced two complications. In patients randomised to surgery, 2.5% had an unscheduled overnight admission following their treatment (see Table 21).

TABLE 35

Procedural complications at time of primary treatment: comparison of surgery with foam sclerotherapy

Later complications

Complications recorded at the time of the 6-week and 6-month assessments are shown in Tables 36 and 37. Estimates of the effect of treatment on complications are summarised across both follow-up time points in Table 38, with ORs comparing surgery with foam sclerotherapy. The overall complication rate was lower for surgery than for foam sclerotherapy at 6 weeks (OR 0.40, 95% CI 0.26 to 0.62; p < 0.001) and at 6 months (OR 0.64, 95% CI 0.44 to 0.92; p = 0.015).

TABLE 36

Complications at 6 weeks: comparison of surgery with foam sclerotherapy

TABLE 37

Complications at 6 months: comparison of surgery with foam sclerotherapy

TABLE 38

Estimates of the effect of treatment on complications: comparison of surgery with foam sclerotherapy

The event rates for cutaneous numbness (6 weeks OR 3.98, 95% CI 2.11 to 7.50; p < 0.001, and 6 months OR 5.39, 95% CI 2.50 to 11.62; p < 0.001) were significantly higher for surgery than for foam sclerotherapy. Wound infection occurred in 9.2% of the surgical patients at 6 weeks – a much higher proportion than the 0.8% of foam patients with wound infection – but clearly this complication only occurred in foam patients who had treatment other than that to which they had been randomised.

However, the rates for lumpiness (6 weeks OR 0.23, 95% CI 0.15 to 0.34; p < 0.001, and 6 months OR 0.18, 95% CI 0.10 to 0.33; p < 0.001), skin staining (6 weeks OR 0.12, 95% CI 0.07 to 0.21; p < 0.001, and 6 months OR 0.16, 95% CI 0.10 to 0.28; p < 0.001), persistent tenderness (6 weeks OR 0.52, 95% CI 0.36 to 0.77; p = 0.001) and headache (6 weeks OR 0.31, 95% CI 0.10 to 0.98; p = 0.047) were all significantly higher for foam sclerotherapy than for surgery. There were no differences for persistent bruising, skin loss/ulceration or development of thread vein at either time point. There was also no difference for backache at 6 weeks. At 6 months, data on wound infection, persistent tenderness, backache and headache were not collected.

Serious adverse events

Eleven SAEs were noted among those randomised to foam. Among these were three DVTs; all were assessed as related to treatment and expected. The other eight SAEs were not related to the foam treatment; full details are given in Table 39. Ten SAEs were noted among those randomised to surgery. Four of these (groin infection, post-operative infection, post-operative haematoma, injury to peroneal nerve) were assessed as being related to treatment. The other six SAEs were not related to treatment (see Table 39).

TABLE 39

Serious adverse events detected up to the time of the 6-months follow-up