PATENCY-2 trial of vonapanitase to promote radiocephalic fistula use for hemodialysis and secondary patency.

OBJECTIVE: Arteriovenous fistulas created for hemodialysis often fail to become usable and are frequently abandoned. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in increasing radiocephalic fistula use for hemodialysis and secondary patency. METHODS: PATENCY-2 was a randomized, double-blind, placebo-controlled trial in patients on or approaching the need for hemodialysis undergoing radiocephalic arteriovenous fistula creation. Of 696 screened, 613 were randomized, and 603 were treated (vonapanitase n = 405, placebo n = 208). The study drug solution was applied topically to the artery and vein for 10 min immediately after fistula creation. The primary endpoints were fistula use for hemodialysis and secondary patency (fistula survival without abandonment). Other efficacy endpoints included unassisted fistula use for hemodialysis, primary unassisted patency, fistula maturation and unassisted maturation by ultrasound criteria, and fistula procedure rates. RESULTS: The proportions of patients with fistula use for hemodialysis was similar between groups, 70% vonapanitase and 65% placebo, (p = 0.33). The Kaplan-Meier estimates of 12-month secondary patency were 78% (95% confidence interval [CI], 73-82) for vonapanitase and 76% (95% CI, 70-82) for placebo (p = 0.93). The proportions with unassisted fistula use for hemodialysis were 46% vonapanitase and 37% placebo (p = 0.054). The Kaplan-Meier estimates of 12-month primary unassisted patency were 50% (95% CI, 44-55) for vonapanitase and 43% (95% CI, 35-50) for placebo (p = 0.18). There were no differences in the proportion of patients with fistula maturation or in fistula procedure rates. Adverse events were similar between groups. Vonapanitase was not immunogenic. CONCLUSIONS: Vonapanitase treatment did not achieve clinical or statistical significance to meaningfully improve radiocephalic fistula surgical outcomes. Outcome in the placebo group were better than in historical controls. Vonapanitase was well-tolerated and safe. TRIAL REGISTRATION: clinicaltrials.gov: NCT02414841 (https://clinicaltrials.gov/ct2/show/NCT02414841).

Frequency and severity of hypersensitivity reactions in patients after VenaSeal™ cyanoacrylate treatment of superficial venous insufficiency.

OBJECTIVE: Hypersensitivity reaction presenting as a distinctive erythematous rash has been reported following VenaSeal™ cyanoacrylate adhesive closure. We report the frequency of hypersensitivity reactions, time to onset, duration, and severity of symptoms in patients treated with cyanoacrylate adhesive closure at a single institution. Patient and procedural factors associated with hypersensitivity reactions were evaluated. METHODS: A combined retrospective/prospective review of cyanoacrylate adhesive closure-treated patients was conducted over five years. Data collected from electronic medical records were reviewed for the presence of hypersensitivity reactions along with the time of onset, duration of symptoms, and severity of reaction. Severity was classified as mild if no treatment or over the counter medication was provided, moderate if steroids were required, and severe if the reaction lasted >30 days or required vein excision. RESULTS: Three hundred and seventy-nine limbs were treated in 286 patients (313 treatment days). Hypersensitivity reactions occurred in 18 patients (5.8% treatments, 6.3% patients). Thirteen were mild (4.2%), four were moderate (1.3%), and one was severe (0.3%). No patient or procedural predictive factors for hypersensitivity reaction were identified other than a trend towards decreased hypersensitivity reactions in patients with Clinical, Etiologic, Anatomic, Pathophysiologic (CEAP) clinical class C4-C6 (p = .06). Second limb treatment on a subsequent day was performed in 27 patients, and no hypersensitivity reactions occurred. Symptom onset time ranged from 1 to 23 days, with a mean of 13 days (confidence interval (CI) ±3.5 days). Duration of symptoms ranged from 3 to 28 days (mean 10.8 CI ±4.9 days). CONCLUSIONS: Hypersensitivity reactions occurred in 6.0% of patients treated with cyanoacrylate adhesive closure, but most were mild and self-limited. Severe reactions were uncommon. No predictive patient or procedural factors were found to be associated with hypersensitivity reactions other than a trend towards decreased risk in patients with advanced CEAP clinical class. Previous cyanoacrylate adhesive closure treatment was not a predictive factor for hypersensitivity reaction in patients undergoing treatment at a later date.

A randomized trial of vonapanitase (PATENCY-1) to promote radiocephalic fistula patency and use for hemodialysis.

OBJECTIVE: Arteriovenous fistulas created in patients with chronic kidney disease often lose patency and fail to become usable. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in promoting radiocephalic fistula patency and use for hemodialysis. METHODS: PATENCY-1 was a double-blind, placebo-controlled trial that enrolled 349 patients on or approaching hemodialysis and being evaluated for radiocephalic arteriovenous fistula creation. Of these, 313 were randomized and 311 treated. Patients were assigned to vonapanitase (n = 210) or placebo (n = 103). The study drug solution was applied topically to the artery and vein for 10 minutes immediately after fistula creation. The primary and secondary end points were primary patency (time to first thrombosis or corrective procedure) and secondary patency (time to abandonment). Tertiary end points included use of the fistula for hemodialysis, fistula maturation by ultrasound, and procedure rates. RESULTS: The Kaplan-Meier estimates of 12-month primary patency were 42% (95% confidence interval [CI], 35-49) and 31% (95% CI, 21-42) for vonapanitase and placebo (P = .25). The Kaplan-Meier estimates of 12-month secondary patency were 74% (95% CI, 68-80) and 61% (95% CI, 51-71) for vonapanitase and placebo (P = .048). The proportions of vonapanitase and placebo patients were 39% and 25% (P = .035) with unassisted use for hemodialysis and 64% and 44% (P = .006) with unassisted plus assisted use. CONCLUSIONS: Vonapanitase treatment did not significantly improve primary patency but was associated with increased secondary patency and use for hemodialysis. Further research is needed to evaluate these end points.

Need for adjunctive procedures following cyanoacrylate closure of incompetent great, small and accessory saphenous veins without the use of postprocedure compression: Three-month data from a postmarket evaluation of the VenaSeal System (the WAVES Study).

PURPOSE: Studies examining cyanoacrylate closure of saphenous veins with the VenaSeal™ System have not allowed concomitant procedures for tributaries at the time of the index procedure. Outside of clinical trials, however, concomitant procedures are frequently performed in conjunction with endovenous ablation. We report on the frequency of need for saphenous tributary treatment three months after cyanoacrylate closure of the treatment of great saphenous vein, small saphenous vein, and/or accessory saphenous vein. METHODS: Fifty subjects with symptomatic great saphenous vein, small saphenous vein, and/or accessory saphenous vein incompetence were treated with no postprocedure compression stockings. Concomitant procedures were not allowed. Treating physicians predicted the type and nature of any concomitant procedures that they would usually perform at the time of ablation, if not limited by the constraints of the study. Evaluations were performed at one week, one and three months and included duplex ultrasound, numeric pain rating scale, revised venous clinical severity score, the Aberdeen Varicose Vein Questionnaire, and time to return to work and normal activities. At the three-month visit, the need for and type of adjunctive procedures were recorded. RESULTS: Complete closure at three months was achieved in 70 (99%) of the treated veins (48 great saphenous veins, 14 accessory saphenous veins, eight small saphenous veins). Revised venous clinical severity score improved from 6.4 ± 2.2 to 1.8 ± 1.5 (P < .001) and Aberdeen Varicose Vein Questionnaire from 17.3 ± 7.9 to 6.5 ± 7.2 (P < .0001). Sixty-six percent of patients underwent tributary treatment at three months. The percentage of patients who required adjunctive treatments at three months was lower than had been predicted by the treating physicians (65% versus 96%, p=.0002). CONCLUSIONS: Closure rates were high in the absence of the use of compression stockings or side branch treatment. Improvement in quality of life was significant, and the need for and extent of concomitant procedures was significantly less than had been predicted by the treating physicians.

Clinical presentation of women with pelvic source varicose veins in the perineum as a first step in the development of a disease-specific patient assessment tool.

OBJECTIVE: Pelvic venous incompetence can cause symptomatic varicose veins in the perineum, buttock, and thigh. Presentation, symptom severity, and response to treatment of pelvic source varicose veins are not well defined. Currently available tools to measure the severity of lower extremity venous disease and its effects on quality of life may be inadequate to assess disease severity in these patients. The purpose of this study was to evaluate the histories, demographics, and clinical presentations of women with pelvic source varicose veins and to compare these data to a population of women with nonpelvic source varicose veins. METHODS: A total of 72 female patients with symptomatic pelvic source varicose veins were prospectively followed up. Age, weight, height, parity, and birth weights of offspring were recorded. Both pelvic source varicose veins and saphenous incompetence were identified by duplex ultrasound. Patients were queried as to their primary symptoms, activities that made their symptoms worse, and time when their symptoms were most prominent. Severity of disease was objectively evaluated using the revised Venous Clinical Severity Score (rVCSS) and 10-point numeric pain rating scale (NPRS). RESULTS: Compared with women without a pelvic source of varicose veins (N = 1163), patients with pelvic source varicose veins were younger (mean, 44.6 ± 8.6 vs 52.6 ± 12.9 years; P < .001), had lower body mass index (mean, 21.9 ± 2.8 vs 25.8 ± 6.2; P < .001), and had larger babies than the U.S. population mean (mean, 3656 ± 450 g vs 3389 ± 466 g; P < .001). The most common symptoms were aching (68%), throbbing (47%), and heaviness (35%). In premenopausal patients, 70% noted that symptoms were worst during menses. NPRS score varied from 0 to 8 (mean, 4.9). The correlation between rVCSS (mean 5.6 ± 1.9) and NPRS was small (r = 0.26; P = .03). There was a modest correlation between older age and lower NPRS scores (r = -0.39; P < .001). CONCLUSIONS: Women with pelvic source varicose veins are a unique subset of patients. They are younger and thinner than those with nonpelvic source varicose veins, have larger infants than the general U.S. population, and have an inverse correlation between age and pain. As the majority of premenopausal patients have increased symptoms during menses, this may be due to hormonal influence. As it is poorly associated with patient-reported discomfort, the rVCSS is a poor tool for evaluating pelvic source varicose veins. A disease-specific tool for the evaluation of pelvic source varicose veins is critically needed, and this study is a first step in that endeavor.

Cyanoacrylate closure of incompetent great, small and accessory saphenous veins without the use of post-procedure compression: Initial outcomes of a post-market evaluation of the VenaSeal System (the WAVES Study).

Purpose Cyanoacrylate closure of the great saphenous vein with the VenaSeal™ Closure System is a relatively new modality. Studies have been limited to moderate-sized great saphenous veins and some have mandated postoperative compression stockings. We report the results of a prospective study of cyanoacrylate closure for the treatment of great saphenous vein, small saphenous veins, and/or accessory saphenous veins up to 20 mm in diameter. Methods Fifty subjects with symptomatic great saphenous vein, small saphenous veins, and/or accessory saphenous veins incompetence were each treated at a single session. Compression stockings were not used post-procedure. Subjects returned to clinic at week 1 and again at one month. Post-procedure evaluations were performed at seven days and one month and included numerical pain rating score, revised venous clinical severity score, the Aberdeen Varicose Vein Questionnaire score, and time to return to work and normal activities. Duplex ultrasound was performed at each visit. Findings Procedural pain was mild (numerical pain rating scale 2.2 ± 1.8). All treated veins (48 great saphenous vein, 14 accessory saphenous veins, and 8 small saphenous veins) had complete closure by duplex ultrasound at seven days and one month. Mean time to return to work and normal activities was 0.2 ± 1.1 and 2.4 ± 4.1 days, respectively. The revised venous clinical severity score was improved to 1.8 ± 1.4 ( p < .001) and Aberdeen Varicose Vein Questionnaire score to 8.9 ± 6.6 ( p < .001) at one month. Phlebitis in the treatment area or side branches occurred in 10 subjects (20%) and completely resolved in all but one subject (2%) by one month; 98% of subjects were "completely" or "somewhat" satisfied, and 2% "unsatisfied" with the procedure at one month, despite the protocol disallowance of concomitant side branch treatment. Conclusions Cyanoacrylate closure is safe and effective for the treatment of one or more incompetent saphenous or accessory saphenous veins. Closure rates were high even in the absence of the use of compression stockings or side branch treatment. Time back to work or normal activities was short and improvements in venous severity scores and QOL were significant, comparing favorably with alternative treatment methods.

Endovenous laser treatment of varicose veins.

Endovenous laser treatment (EVLT) has become a standard therapy for the treatment of superficial venous insufficiency. It offers a rapid, office-based therapy with minimal patient downtime and an easier recovery than traditional surgical treatment. EVLT is effective and durable and can successfully treat saphenous truncal insufficiency and accessory branches with low complication rates. EVLT can increase patient satisfaction and enable the treatment of a wider variety of patients with a more efficient procedure compared with traditional techniques.

Foam sclerotherapy for the treatment of superficial venous insufficiency.

Foam sclerotherapy has been refined over the past decade to become a safe and effective treatment for varicose veins and venous insufficiency. Using duplex ultrasound guidance, it can be used to treat large and small varicosities, saphenous trunks, incompetent perforating veins, and venous stasis ulcerations. Serious complications are rare, and in experienced hands, efficacy rivals that of traditional surgical ligation and stripping. Disadvantages of the technique are the need in many cases for more than one treatment session, and lack of US Food and Drug Administration approval of all currently available sclerosants. Foam sclerotherapy offers advantages of low cost, quick patient recovery, and ease of use; as such, it is an important tool for modern vein treatment.

Endovenous laser treatment of the small [corrected] saphenous vein: efficacy and complications.

OBJECTIVE: The study was conducted to assess the efficacy and rate of complications of endovenous laser treatment (EVLT) of the short saphenous vein (SSV). METHODS: During a 17-month period, 210 (187 patients) with SSV incompetence documented by duplex ultrasound studies were treated with EVLT using a 980-nm diode laser. Duplex ultrasound examinations were performed on the day of the procedure, within the first week, and 2 to 11 months after the procedure (mean follow-up, 4 months). Clinical examinations were performed at 2 weeks and 6 weeks. Patients were assessed for deep venous thrombosis (DVT), nerve injury, and resolution of symptoms. RESULTS: All procedures were technically successful, and in the 126 patients (60%) who completed final follow-up scanning, 96% of SSVs remained closed. Three patients (1.6%) had numbness at the lateral malleolus at the 6-week follow-up. DVT, defined as a tail of thrombus protruding into the popliteal vein, was not detected in any limbs at the initial duplex study, but was noted in 12 limbs (5.7%) at the 1-week follow-up examination. Nine patients were treated with 3 days to 3 months of fractionated heparin and Coumadin (Bristol-Myers Squibb, Princeton, NJ), and there were no DVT extensions or pulmonary emboli. The anatomic configuration of the saphenopopliteal junction was the only factor predictive of DVT. CONCLUSIONS: Intermediate-term results of EVLT of the SSV demonstrate that the technique is effective at eliminating SSV reflux and affording symptomatic relief. The incidence of nerve injury is low, but the incidence of DVT is higher than reported for the great saphenous vein. Anatomic features of the SSV may predict patient risk for DVT.

Is early postoperative duplex scan surveillance of leg bypass grafts clinically important?

PURPOSE: The typical leg bypass surveillance program begins with a duplex scan evaluation of the vein graft 3 months after surgery; studies are repeated every 3 months during the first year of follow-up and are fully reimbursed by our Medicare carrier. Some authors have recommended early (before discharge or first postoperative visit) duplex scanning to identify high-risk grafts. However, the natural history of velocity disturbances detected with early scans is unclear, and furthermore, such studies are not reimbursed by Medicare. METHODS: We reviewed all infrainguinal vein bypass grafts prospectively entered into a surveillance protocol that included an early (<6 weeks) duplex scan study. Routine completion angiography was performed at the initial operation in all patients. Early duplex scan results, the need for graft revision, and detailed follow-up of these bypass grafts were analyzed. RESULTS: Early duplex scans were performed in 224 bypass grafts placed in 204 patients. Early scans were abnormal (peak systolic velocity [PSV], >200 cm/s) in 58 grafts (26%). Six grafts of the 58 (10.3%; 2.7%) with an early abnormal duplex scan and unrepaired defects occluded during the follow-up period. Thirty grafts were revised on the basis of the initial early scan; 23 of these revisions were performed for critical or rapidly progressive lesions in the first 3 postoperative months. Seven lesions progressed more slowly and were repaired at a mean of 8 months after surgery. Interestingly, 22 flow abnormalities (37%) resolved or stabilized despite a PSV of more than 300 cm/s in six cases (27%). Clear duplex scan evidence of regression or progression of these early flow abnormalities occurred within 3 months in 51/58 cases (88%). A total of 68 grafts (30%) were revised during the entire study period; 30 of these (44%) were on the basis of the early abnormal scan. CONCLUSION: Despite normal completion arteriography, early graft velocity abnormalities are strikingly common and were detected in 26% of the 224 infrainguinal vein grafts in this series. These lesions were clinically important because 52% necessitated revision. Surprisingly, however, 38% of these early flow disturbances resolved, despite a PSV of more than 300 cm/s in 27% of cases. Early duplex scan surveillance singularly detects a clinically significant subgroup of grafts that need revision. The possible origin of these early lesions deserves further inquiry, but on the basis of its clinical yield, we recommend that early duplex scan surveillance of infrainguinal bypass grafts should be routine and should be considered for Medicare reimbursement.