Representative test samples from the D-Stat Silver product family (Dry, Wrap and Thrombix Silver) demonstrated an antimicrobial effect in the following laboratory testing: AATCC Test Method 100-2004 against Candida albicans, VRE, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, MRSA, and MRSE. Zone of Inhibition laboratory testing demonstrated the following: Culture Name Candida albicans Average of Zone of Inhibition Results (Reported in mm) 40* Do not place the D-Stat Dry Silver into blood vessels. Extensive intravascular clotting and even death may result. The D-Stat Dry Silver is supplied sterile for single use only. Do not re-sterilize. Do not use D-Stat Dry Silver as a replacement for absorbable hemostats. This product contains nonabsorbable materials and is not intended to be left in the body. PRECAUTIONS Do not use the D-Stat Dry Silver if the packaging has been damaged. The safety and effectiveness of the D-Stat Dry Silver have not been established in children and pregnant women who have undergone a diagnostic endovascular procedure involving a 4-6 Fr. sheath. Enterococcus faecalis (VRE) 29 Escherichia coli 29 Klebsiella pneumoniae 33 Pseudomonas aeruginosa 29 Staphylococcus aureus (MRSA) 33 Staphylococcus epidermidis (MRSE) Enterococcus faecalis 38 Do not touch the D-Stat Dry Silver lyophilized pad with wet gloves or expose the pad to liquid. Absorption of the liquid and destruction of the pad will result. 27 Do not leave the D-Stat Dry Silver pad or adhesive bandage applied for more than 24 hours. Skin irritation may result. Staphylococcus aureus 34 Staphylococcus epidermidis 38 *Product sample reconstituted with 1mL of sterile water D-Stat Dry Silver has not been clinically tested for its ability to reduce local infection, catheter-related bloodstream infections (CRBSI) and skin colonization of microorganisms commonly related to CRBSI. No clinical trials have been performed with D-Stat Silver products. These products have not been shown to be more clinically effective than a dressing not containing an antimicrobial agent. Sodium carboxymethylcellulose, also known as cellulose gum or CMC, serves as the matrix for the lyophilized pad and as a suspension agent for the thrombin. The D-Stat Dry Silver should not be used in the presence of infection. It should be used with caution in contaminated areas of the body. When removing the D-Stat Dry Silver lyophilized pad and the adhesive bandage, do not disrupt the clot by physical manipulation. If the pad adheres to the puncture site, irrigate the pad with non-heparinized saline and carefully remove it. ADVERSE EVENTS A recognized rare potential reaction associated with the use of bovine derived thrombin is the development of inhibitory antibodies, which interferes with hemostasis. RANDOMIZED MULTI-CENTER INVESTIGATION Results are presented below for the randomized trial performed to evaluate the safety and effectiveness of the DStat Dry hemostatic bandage (no silver) in patients undergoing diagnostic endovascular catheterization procedures that utilized a 4F, 5F or 6F introducer sheath. Hemostasis is achieved by the physiological coagulationinducing properties of the lyophilized pad combined with manual compression. This data is applicable to the D-Stat Dry Silver as nonclinical bench and in vivo animal testing has demonstrated similar hemostatic performance profiles for the D-Stat Dry D-Stat Dry Silver Hemostatic Bandage The D-Stat Dry Silver and D-Stat Dry Clear Silver have been and D-Stat Dry Silver products. Topical Hemostat sterilized with irradiation. The purpose of this study was to evaluate the safety and Model 3000 effectiveness of the D-Stat Dry hemostatic bandage in patients undergoing diagnostic endovascular catheterization D-Stat® Dry Clear Silver Hemostatic procedures that utilized a 4F, 5F or 6F introducer sheath. INDICATIONS Bandage Topical Hemostat This prospective, multi-center (5 centers), randomized, nonThe D-Stat Dry Silver is applied topically as an adjunct to significant risk investigation evaluated a total of three manual compression and is indicated for the control of Model 3005 hundred seventy-six (376) subjects randomized at a 1:1 surface bleeding from vascular access sites and Instructions For Use ratio to treatment with either D-Stat Dry with manual percutaneous catheters or tubes and reducing the time-tocompression (the Investigation Group) or standard manual hemostasis in patients undergoing diagnostic endovascular USA CAUTION compression alone (the Control Group). Of the 376 procedures utilizing 4-6 Fr. introducer sheaths. D-Stat Dry Federal (USA) law restricts this device to sale by or on the randomized patients, 187 (49.73%) were randomized to the Silver contains silver chloride to prevent microorganisms order of a physician. commonly encountered in the clinical setting from colonizing Investigation Group and 189 (50.27%) were randomized to DEVICE DESCRIPTION the Control Group. on the pad. Each D-Stat Dry Silver hemostatic bandage (D-Stat Dry A total of 3 major adverse events (1 D-Stat Dry, 2 Standard CONTRAINDICATIONS Silver) consists of the following components: Compression) were reported during the randomized The D-Stat Dry Silver is contraindicated in persons with Lyophilized pad consisting of thrombin, silver investigation. All of these major adverse events were known sensitivity to bovine-derived materials. chloride, sodium carboxymethylcellulose and calcium determined to be unrelated to post procedure methods. WARNINGS chloride in a nonwoven gauze Table 1 presents the distribution of major adverse events for Adhesive bandage the treatment groups. No statistical differences were The use of topical bovine thrombin preparations has observed between groups. occasionally been associated with abnormalities in Thrombin is a protein substance produced through a hemostasis ranging from asymptomatic alterations in Table 1: Distribution of Major Adverse Events conversion reaction in which prothrombin of bovine origin is laboratory determinations, such as prothrombin time (PT) Treatment Group activated by tissue thromboplastin of bovine origin in the and partial thromboplastin time (PTT), to severe bleeding Investigation Control presence of calcium chloride. Thrombin contains no or thrombosis which rarely have been fatal. These Group Group (n=187) (n=189) p value preservative and has been chromatographically purified. hemostatic effects appear to be related to the formation Thrombin requires no intermediate physiological agent for its of antibodies against bovine thrombin and/or factor V % N % n reaction. It converts fibrinogen directly to fibrin. This product which in some cases may cross react with human factor Pseudoaneurysm 0.0 0 0.5 1 1.000* contains not less than 200 units of bovine derived thrombin. V, potentially resulting in factor V deficiency. Repeated clinical applications of topical bovine thrombin increase This product contains no more than 500 mcg of silver Retroperitoneal bleed 0.5 1 0.0 0 0.497* the likelihood that antibodies against thrombin and/or content from the silver chloride form. In the presence of factor V may be formed. Consultation with an expert in Other (rhythm disturbance) 0.0 0 0.5 1 1.000* fluids (i.e., blood and wound fluids), ionic silver is released coagulation disorders is recommended if a patient from the silver chloride to prevent microorganisms All adverse events 0.5 1 1.1 2 0.0001** exhibits abnormal coagulation laboratory values, commonly encountered in the clinical setting from colonizing abnormal bleeding, or abnormal thrombosis following the * Calculated using Fisher’s Exact Test. on the pad. Ionic silver, an atom of silver that is missing one use of topical thrombin. Any interventions should consider ** Calculated using Blackwelder’s Test of Non-inferiority. electron, provides the antimicrobial property by altering the the immunologic basis of this condition. Patients with This clinical investigation yielded a low major adverse event protein structure and preventing bacterial cells from carrying antibodies to bovine thrombin preparations should not be out normal functions. rate of 0.5% (1/187) in the Investigation Group and 1.1% re-exposed to these products. (2/189) in the Control Group, and the Investigation Group ® was demonstrated to be statistically non-inferior to the Control Group. In addition, no unanticipated adverse device effects were observed. This trial demonstrated that use of DStat Dry as an adjunct to standard manual compression in the intended study population was safe. A total of three minor adverse events (1 D-Stat Dry, 2 Standard Compression) were reported during this investigation as described in Table 2. Carefully inspect the D-Stat Dry Silver packaging (foil pouch and foil sealed inner tray) and components for damage prior to use. 3. Table 2: Distribution of Minor Adverse Events Two Hand Application Procedure (recommended) 1. Using sterile technique, open the foil pouch and transfer the tray into the sterile field. 2. Peel back the lid of the tray completely. On a sterile drape, turn the tray upside down and tap on the bottom to detach the pad from the tray. 4. Minor Adverse Events Non-treated pseudoaneurysm or non-treated arteriovenous (AV) fistula documented by ultrasound Access site hematoma >6cm Investigation Group n = 187 % n Control Group n = 189 % n Combined Groups n = 376 % n 0.0 0.0 0.5 1 0.3 1 0.5 1 0.5 1 0.5 2 The primary effectiveness endpoint of this clinical trial was to demonstrate a reduced time-to-hemostasis with D-Stat Dry as compared with standard manual compression in patients with a bleeding femoral arterial access site subsequent to a diagnostic endovascular catheterization procedure. Time-to-hemostasis was defined as: the time from the removal of the femoral artery sheath and initiation of compression at the femoral arterial access site to the time hemostasis is first observed at the femoral arterial access site, so long as hemostasis was maintained for at least 5 consecutive minutes following the first observation of hemostasis. Conduct of this trial successfully demonstrated the effectiveness of D-Stat Dry in the overall reduction in TimeTo-Hemostasis as evidenced in the mean TTH observed for the Investigation Group of 7.8 minutes compared to the observed mean TTH of 13.0 minutes for the Control Group. As previously stated, this difference is significant with a pvalue of 0.001. Further, a 50% reduction in the median Time-To-Hemostasis (6 minutes) was observed in the Investigation Group when compared to the Control Group (12 minutes). 3. 4. 5. 6. 7. Table 3: Time-To-Hemostasis (TTH) Results n Median TTH (mins) Mean TTH (mins)* ± Standard Deviation Range (min/max) p-value* *Wilcoxon’s Rank-sum Test 8. Note that the safety and effectiveness of D-Stat Dry has not been established in the following patient populations: 9. Using sterile technique, open the adhesive bandage packaging and transfer the bandage into the sterile field. With one hand, apply occlusive pressure proximal to the arterial puncture site. Slowly ease off occlusive pressure to firm pressure, and remove the sheath with the other hand. Allow a ”dime-sized” amount of blood to form on the skin puncture site. Immediately return to occlusive pressure. With the other hand, place the pad directly over the 7. skin puncture site and apply firm, non-occlusive pressure. Maintain occlusive pressure proximal to the arterial puncture site. Slowly, over a 1-3 minute timeframe, release occlusive pressure while maintaining firm, non-occlusive pressure for the recommended hold time. For diagnostic patients utilizing 4-6F sheaths, hold pressure for a minimum of 6 minutes or until 8. hemostasis is achieved. For anticoagulated patients, hypertensive patients 9. or patients on IIb/IIIa’s, Lovenox or Plavix, follow institutional guidelines for time of sheath pull and then apply pressure for a minimum of 10 minutes or until hemostasis is achieved. For Angiomax patients without renal impairment, wait 1 hour or longer to pull the sheath and then hold for a minimum of 10 minutes or until hemostasis is achieved. For dialysis patients, follow the institutional ACT protocol and then hold for a minimum of 10 minutes or until hemostasis is achieved. While leaving the D-Stat Dry Silver pad in place, slowly release pressure and confirm hemostasis. If hemostasis has not been achieved, reapply firm, nonocclusive pressure until hemostasis is confirmed. Note: Removing the pad may disrupt the newly formed clot. Once hemostasis has been confirmed, apply the adhesive bandage directly on the skin over the D-Stat Dry Silver access site. If desired, the adhesive bandage may be left in place for up to 24 hours. Patients undergoing an interventional procedure via the same sheath through which the study procedure was performed Patients who have a posterior wall stick during access of 10. the femoral artery Precaution: Do not leave the adhesive bandage Patients who have multiple (>1) tissue tracts made during applied for more than 24 hours. Skin irritation may access of the femoral artery result. Patients who have been heavily anticoagulated (ACT >400 sec) at the end of the catheterization procedure Precaution: When removing the D-Stat Dry Silver Patients receiving Angiomax or Refludan lyophilized pad and the adhesive bandage, do not Patients who have arterial introducer sheaths of <4F and disrupt the clot by physical manipulation. If the pad >6F adheres to the puncture site, irrigate the pad with non Patients who have a large hematoma (>6cm in diameter) heparinized saline and carefully remove it. present prior to topical sealing Note: Table 4 below offers minimum guidelines to Patients with “uncontrolled” blood pressure (systolic assist in determination of ambulation times for >180mm Hg / diastolic >110mm Hg) at end of diagnostic endovascular patients; however, these catheterization procedure guidelines should not supercede clinical judgment Patients with a known bleeding disorder, including based on the medical condition of the individual thrombocytopenia (<100,000 platelet count), patient. thrombasthenia, hemophilia, von Willebrand’s disease or Table 4: Ambulation Guidelines anemia (Hgb <10g/dL; Hct <30) Medication Sheath Women who are known or suspected to be pregnant or Ambulation Guidelines Status Size lactating Not Anti1.5 to 2.5 hours bed rest Patients receiving coumadin/warfarin with a documented 4, 5, 6 Fr. coagulated post sheath removal baseline INR >2.0 Anti2.0 to 3.0 hours bed rest Patients receiving thrombolytic therapy (e.g., strepto4, 5, 6 Fr. coagulated post sheath removal kinase, urokinase, t-PA) within the last 24 hours Patients with known allergies to bovine-derived products One Hand Application Procedure CLINICAL PROCEDURE 1. Using sterile technique, open the foil pouch and The D-Stat Dry Silver should be used by physicians trained transfer the tray into the sterile field. on the procedures for which the device is intended. The 2. Peel back the lid of the tray completely. On a sterile techniques and procedures described do not represent ALL drape, turn the tray upside down and tap on the medically acceptable protocols, nor are they intended as a bottom to detach the pad from the tray. substitute for the physician's experience and judgment in Precaution: Do not touch the D-Stat Dry Silver treating any specific patient. All available data, including the lyophilized pad with wet gloves or expose the D-Stat patient’s signs and symptoms and other diagnostic test Dry Silver pad to liquid. Absorption of the liquid and results, should be considered before determining a specific destruction of the pad will result. treatment plan. ©2011 Vascular Solutions, Inc. 2 6. Precaution: Do not touch the D-Stat Dry Silver lyophilized pad with wet gloves or expose the D-Stat Dry Silver pad to liquid. Absorption of the liquid and destruction of the pad will result. A summary of this data is presented in Table 3 below. Treatment Group Investigation Control Group Group 187 189 6.0 12.0 7.8 13.0 3.0 6.4 6, 22 6, 31 0.001 5. Using sterile technique, open the adhesive bandage packaging and transfer the bandage into the sterile field. Place the pad directly over the puncture site and apply firm, non-occlusive pressure. Remove the sheath according to institutional protocol, and allow a ”dime-sized” amount of blood to come into contact with the pad. Maintain firm, non-occlusive pressure over the puncture site for the recommended time. For diagnostic patients utilizing 4-6F sheaths, hold pressure for a minimum of 6 minutes or until hemostasis is achieved. For anticoagulated patients, hypertensive patients or patients on IIb/IIIa’s, Lovenox or Plavix, follow institutional guidelines for time of sheath pull and then apply pressure for a minimum of 10 minutes or until hemostasis is achieved. For Angiomax patients without renal impairment, wait 1 hour or longer to pull the sheath and then hold for a minimum of 10 minutes or until hemostasis is achieved. For dialysis patients, follow the institutional ACT protocol and then hold for a minimum of 10 minutes or until hemostasis is achieved. While leaving the pad in place, slowly release pressure and observe the puncture site to determine if hemostasis has been achieved. If hemostasis has not been achieved, reapply firm, non-occlusive pressure over the puncture site until hemostasis is confirmed. Note: Removing the pad may disrupt the newly formed clot. Once hemostasis has been confirmed, apply the adhesive bandage over the pad. If desired, the adhesive bandage may be left in place for up to 24 hours. Precaution: Do not leave the adhesive bandage applied for more than 24 hours. Skin irritation may result. Precaution: When removing the D-Stat Dry Silver lyophilized pad and the adhesive bandage, do not disrupt the clot by physical manipulation. If the pad adheres to the puncture site, irrigate the pad with nonheparinized saline and carefully remove it. Note: Table 5 below offers minimum guidelines to assist in determination of ambulation times for diagnostic endovascular patients; however, these guidelines should not supercede clinical judgment based on the medical condition of the individual patient. Table 5: Ambulation Guidelines Medication Status Not Anticoagulated Anticoagulated Sheath Size Ambulation Guidelines 4, 5, 6 Fr. 1.5 to 2.5 hours bed rest post sheath removal 4, 5, 6 Fr. 2.0 to 3.0 hours bed rest post sheath removal 3M™ Tegaderm™ Transparent Film Dressing Frame Style 1626, 1627, 1628, 1629, 1630, 1634, 1622W, 1623W, 1624W, 1626W, 9505W, 9506W Description: Tegaderm™ Film consists of a thin film backing with a non-latex, hypoallergenic adhesive. Tegaderm™ Film with Border is notched and reinforced with soft cloth tape to provide a better seal around catheters and other devices. The dressing is breathable, allowing good oxygen and moisture vapor exchange. It is waterproof and impermeable to liquids, bacteria, and viruses. *An intact dressing protects the site from outside contamination. *In vitro testing shows that the film of Tegaderm™ and Tegaderm™ HP dressings provides a viral barrier from viruses 27nm in diameter or larger while the dressing remains intact without leakage. Indications: Tegaderm™ Film can be used to cover and protect catheter sites and wounds, to maintain a moist environment for wound healing or to facilitate autolytic debridement, as a secondary dressing, as a protective cover over at-risk skin, to secure devices to the skin, to cover first and second degree burns, and as a protective eye covering. Do not use the dressing as a replacement for sutures and other primary wound closure methods. 42-0716-01 rev F 08/11 Precautions: 1. Stop any bleeding at the site before applying the dressing. 2. Do not stretch the dressing during application as tension can cause skin trauma. 3. Make sure the skin is clean, free of soap residue and lotion and allowed to dry thoroughly before applying the dressing to prevent skin irritation and to ensure good adhesion. 4. The dressing may be used on an infected site, only when under the care of a health care professional. 5. Antimicrobial ointments containing polyethylene glycols may compromise the strength of the Tegaderm™ HP Transparent Film Dressings. 6. Tegaderm™ Transparent Dressings should not be resterilized by gamma, E-beam or steam methods. Instructions for Use: Refer to figures. If you have any questions or comments, contact the 3M Health Care Customer Help Line at 1-800-228-3957 OR GO TO WWW.3M.COM. LIMITED WARRANTY Vascular Solutions, Inc. warrants that the D-Stat Dry Silver hemostatic bandage is free from defects in workmanship and materials prior to the stated expiration date. Liability under this warranty is limited to refund or replacement of any product which has been found by Vascular Solutions, Inc. to be defective in workmanship or materials. Vascular Solutions, Inc. shall not be liable for any incidental, special, or consequential damages arising from the use of the D-Stat Dry Silver hemostatic bandage. Damage to the product through misuse, alteration, improper storage, or improper handling shall void this limited warranty. No employee, agent, or distributor of Vascular Solutions, Inc. has any authority to alter or amend this limited warranty in any respect. Any purported alteration or amendment shall not be enforceable against Vascular Solutions, Inc. THIS WARRANTY IS EXPRESSLY IN LIEU OF ALL OTHER WARRANTIES, EXPRESSED OR IMPLIED, INCLUDING ANY WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE OR ANY OTHER OBLIGATION OF VASCULAR SOLUTIONS, INC. PATENTS AND TRADEMARKS International and U.S. patents pending. D-Stat® is a registered trademark of Vascular Solutions, Inc. ©2011 Vascular Solutions, Inc. 3 42-0716-01 rev F 08/11 ©2011 Vascular Solutions, Inc. 4 42-0716-01 rev F 08/11