A Prospective, Randomized Trial of Topical Hemostasis Patch Use following Percutaneous Coronary and Peripheral Intervention
- Volume 20 - Issue 11 - November, 2008
- Posted on: 11/3/08
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ABSTRACT: The use of topical hemostasis patches has grown rapidly despite a paucity of evidence supporting their clinical utility. We performed a randomized, controlled trial to assess the efficacy of a topical hemostasis patch as a means to accelerate vascular hemostasis following percutaneous intervention. One hundred fifty (150) patients undergoing coronary or peripheral intervention through a 6 Fr femoral arterial sheath were randomized to sheath removal with either: (1) manual pressure and adjunctive use of a patch incorporating a polysaccharide based procoagulant material (SafeSeal Patch, Possis Medical Inc.); or (2) conventional manual pressure alone. Sheaths were removed when the activated clotting time (ACT) fell to ≤ 250 seconds. Patients ambulated 2 hours after hemostasis was achieved. Time to hemostasis (duration of compression required until cessation of bleeding following sheath removal) was significantly lower in the hemostasis patch arm (11.8 ± 3.6 vs. 13.8 ± 5.8 minutes; p = 0.02). Attainment of hemostasis in < 15 minutes was also more likely among patients randomized to the hemostasis patch rather than manual compression alone (odds ratio = 2.5; 95% confidence intervals 1.2, 5.1; p = 0.014). The median time to ambulation (total duration from the end of the interventional procedure to ambulation) was significantly reduced among patients in the hemostasis patch arm (2.8 vs. 3.8 hours; p = 0.03). Bleeding complications were uncommon and did not differ between the study arms. In conclusion, this trial supports the concept that the polysaccharide-based SafeSeal Patch enhances access site hemostasis following endovascular intervention.
J INVASIVE CARDIOL 2008;20:579–584
The manufacture and use of topical hemostasis patches, which serve as adjuncts to manual compression to accelerate vascular hemostasis following percutaneous diagnostic and interventional procedures, has grown rapidly over the past few years. Hemostasis patches are promoted as a means to allow arterial sheath removal at higher levels of anticoagulation, shorten the time required to achieve hemostasis after sheath removal and reduce overall postprocedural bed rest time compared to conventional manual compression alone.1,2 At present, 10 competing topical patches, each incorporating one or more of a variety of procoagulant materials, have received United States Food and Drug Administration (FDA) clearance for clinical use. Despite the increasing popularity of these devices, prospective data supporting their utility and safety remains scant. To investigate whether the touted advantages of hemostasis patches might translate into actual clinical benefit, we designed a prospective, randomized, controlled trial to assess the efficacy of one such topical hemostasis patch incorporating a polysaccharide-based procoagulant (SafeSeal Patch, Possis Medical, Inc., Minneapolis, Minnesota) following endovascular intervention.
Patients. Patients 18 years of age or older who underwent percutaneous coronary or peripheral arterial intervention through a 6 Fr femoral arterial sheath at our institution from May, 2007 to October, 2007 were eligible. The protocol was approved by the Research Subjects Review Board at our institution. Patients gave written informed consent for participation in the trial prior to their catheterization procedure, and randomization occurred immediately following completion of the endovascular intervention.
Patients were excluded from the study if any of the following conditions were present: 1) presence of a large (> 4 cm) hematoma or persistent bleeding around the vascular sheath prior to randomization; 2) previous arteriovenous fistula or pseudoaneurysm in the ipsilateral femoral artery; 3) history of bleeding diathesis or coagulopathy; 4) preprocedural hemoglobin level < 9 g/dl; 5) inability to ambulate at baseline; 6) known allergy to any of the materials used in the SafeSeal Patch; 7) female patients known to be pregnant or lactating; 8) evidence of ongoing systemic or cutaneous infection; 9) uncontrolled blood pressure following the intervention (systolic blood pressure > 180 or diastolic blood pressure > 110); or 10) current enrollment in another ongoing investigational drug/device trial.
Study protocol. All patients were treated with aspirin therapy prior to their procedure, and the selection of additional anticoagulation and antiplatelet therapy during the procedure was at the discretion of the operating physician. Patients were randomized in a 1:1 fashion in permuted blocks of 20 patients to sheath removal using either: 1) manual pressure with adjunctive use of the SafeSeal hemostasis patch, or 2) conventional manual pressure alone.
Prior to sheath removal, all patients underwent angiographic imaging of the femoral artery access site to document the location of sheath insertion within the femoral artery. An activated clotting time (ACT) was obtained and the arterial sheath was removed immediately if the ACT was < 250 seconds. If the initial ACT was > 250 seconds, the ACT was repeated on an hourly basis until the 250-second threshold was reached. The SafeSeal patch was used in accordance with the manufacturer’s instructions. In both study groups, compression was performed by experienced catheterization laboratory personnel who were not study investigators; strict adherence to the following protocol was observed: Manual pressure was applied continuously for 10 minutes. After 10 minutes, pressure was decreased, and if hemostasis (defined as the complete absence of any bleeding or oozing from the access site) had not been achieved, pressure was continued and the site was reassessed for hemostasis in a similar fashion every 5 minutes.
After complete hemostasis was achieved, patients were kept on bed rest with the head of bed elevated to an angle of ≤ 30 degrees for 2 hours. The groin site was monitored by the nursing staff in accordance with hospital protocol. Vital signs, the groin site and distal extremity pulses were monitored during bed rest every 15 minutes for the first hour and every 30 minutes during the second hour. If bleeding reoccurred such that manual pressure was required for a period of > 5 minutes to reestablish hemostasis, bed rest was extended for an additional 2 hours from the time that hemostasis was reestablished.
All patients ambulated ≥ 25 feet under supervision 2 hours after final hemostasis had been obtained. No patient was unable to ambulate at 2 hours. A complete blood count was checked and the groin site assessed the morning following the procedure. Any patient with a visible and/or palpable hematoma > 4 cm in diameter, a new femoral bruit or a drop in hemoglobin or hematocrit of > 20% relative to baseline underwent duplex ultrasound examination of the access site. All patients remained in the hospital overnight following their intervention.
Definition of endpoints. The prespecified primary endpoint was the time to hemostasis, defined as the time interval from sheath removal to termination of bleeding or oozing from the femoral artery access site. If recurrent bleeding from the sheath site occurred following initial hemostasis, the timing and duration of additional compression required to reestablish complete hemostasis were also recorded.
The secondary endpoints included the time to ambulation and the incidence of major and minor hemorrhagic complications in each study arm. Time to ambulation was defined as the time interval from the end of the angioplasty procedure (as determined by the time that the final angiographic image was obtained) to the time that the patient ambulated. Thrombolysis in myocardial infarction (TIMI) major bleeding was defined as a a postprocedural drop in hemoglobin of ≥ 5 g/dl or an absolute decrease in hematocrit of ≥ 15%.3 In addition, the occurrence of any of the following clinical events was also considered to represent major bleeding: the development of a large hematoma (> 4 cm in diameter); formation of an arteriovenous fistula or pseudoaneurysm confirmed by vascular ultrasound; retroperitoneal hemorrhage; or need for surgical repair of the access site for any reason. TIMI minor bleeding was defined as a postprocedural drop in hemoglobin of 3–5 g/dl or an absolute decrease in hematocrit of ≥ 9% not associated with any of the above clinical events. The incidence of small hematoma formation, defined as a visible or palpable mass of ≤ 4 cm in diameter at the sheath insertion site without associated sequelae, was also recorded.
Statistics. To provide at least 80% power to detect a difference of 2.5 minutes in the average time to hemostasis between the two treatment arms at the 0.05 significance level, and assuming a standard deviation of 5 minutes or less for each arm, a total of 150 patients (75 per treatment arm) was required. Univariate comparisons between the study arms for categorical variables were performed using the chi-square test or Fisher’s exact test when at least one expected cell count was < 5. For continuous variables, the Wilcoxon rank-sum test was used. A two-tailed p-value of < 0.05 was considered the threshold for statistical significance. Subgroup analysis to assess the univariate relationships between several preselected baseline clinical and procedural variables and time to hemostasis (treated as a dichotomous variable of < 15 minutes versus ≥ 15 minutes) was performed with determination of the odds ratios (OR) and 95% confidence intervals (CI) for each variable.
Stepwise multivariate logistic regression analysis was performed to determine if observed baseline differences between the study and control arms might have influenced the relationship between treatment assignment and the primary study endpoint. The variables of gender, history of hypertension, ACT at the time of sheath removal and treatment assignment were entered into the model, and the OR with a 95% CI examining the likelihood that each variable was independently associated with a time to hemostasis of < 15 minutes was determined. The ACT at the time of sheath removal was treated as a continuous variable. Wald chi-square estimates were used to assess statistical significance.
Patient population. A total of 150 patients were enrolled, with 75 patients randomized to each treatment arm. All patients received their assigned treatment with no crossovers. Baseline demographic characteristics are displayed in Table 1 and procedural variables are provided in Table 2. While the treatment groups were well matched for most variables, there was a significantly lower proportion of women and patients with a history of hypertension in the hemostasis patch group. Despite the gender difference, there were no differences in mean body weight or body mass index between the groups, and there were no differences in systolic or diastolic blood pressure between the study groups at the time of arterial sheath removal. In addition, the mean ACT at the time of sheath removal was significantly higher among patients randomized to the hemostasis patch arm (213 ± 26 vs. 202 ± 27 seconds; p = 0.01).