PubMed Health⌕ Search

Biomedical subjects

Charles P Semba

Publications and source records attributed to Charles P Semba.

16 recordsLinked to original sources
PubMed2006

Alteplase for the treatment of central venous catheter occlusion in children: results of a prospective, open-label, single-arm study (The Cathflo Activase Pediatric Study).

PURPOSE: Alteplase is approved for use in the restoration of function to occluded central venous access devices (CVADs); however, there are few prospective studies in children. This study was undertaken to evaluate the safety and efficacy of alteplase in the treatment of CVAD occlusions in a pediatric population. MATERIALS AND METHODS: A prospective, multicenter, open-label, single-arm study evaluating a maximum of two doses (< or =2 mg per dose) of alteplase was performed in pediatric patients. Inclusion criteria included patient age less than 17 years with an occluded CVAD (single-, double-, and triple-lumen catheter or implanted port). Patients with hemodialysis catheters, those with known mechanical occlusion, or those considered at high risk for bleeding or embolization were excluded. Assessment of function was made 30 and 120 minutes (if required) after each dose. The primary objective of the study was to evaluate the safety of alteplase as measured by the incidence of intracranial hemorrhage (ICH); secondary objectives included the evaluation of specific targeted serious adverse events and efficacy of alteplase in the restoration of catheter function. RESULTS: A total of 310 patients (174 male patients, 136 female patients; mean age, 7.2 years; range, 0.04-18.3 y) were treated; 55 of the patients (17.7%) were younger than 2 years of age. No patients experienced ICH (95% CI, 0%-1.2%). Nine serious adverse events were noted in eight patients (2.6% incidence), two of which were attributed by the investigator to study drug administration (one case of sepsis and one case of a ruptured catheter lumen). The cumulative rate of restoration of CVAD function after serial administration of a maximum of two instillations of alteplase, each with a maximum dwell time of 120 minutes, was 82.9% (95% CI, 78.2%-86.9%). Similar rates of catheter function restoration were seen among all catheter types studied; there were no clinically meaningful differences among age or sex subgroups. CONCLUSION: The administration of alteplase is safe and effective for the restoration of function to CVADs in pediatric patients.

Adolescent↗
PubMed2005

Alteplase stability and bioactivity after low-power ultrasonic energy delivery with the OmniSonics resolution system.

PURPOSE: Low-power ultrasonic (US) energy is capable of clot dissolution in vivo. The combination of US energy plus alteplase may further accelerate clot lysis; however, the effects of cavitation could potentially denature and inactivate the lytic protein. The purpose of this study was to determine the bioactivity and stability of alteplase when exposed to US energy with use of a novel intravascular US wire in an in vitro model. MATERIALS AND METHODS: The model consisted of a 6.4-mm-diameter silicone tube closed at one end and filled with alteplase (1 mg/mL) in a water bath (37 degrees C). A 95-cm US wire (0.025-inch diameter, 20 kHz) was inserted into the tube and connected to a variable power generator. The wire delivers low-power acoustic energy 360 degrees around its 20-cm active length and was irrigated by a continuous infusion of purified water. Fresh 6-mL alteplase aliquots were exposed to US energy and tested in duplicates. Zero (control), 1 W, or 2 W of energy was delivered to individual test samples for zero (control), 0.5, 3, or 6 minutes. Alteplase samples were assayed for optical clarity and protein concentration with use of UV spectrophotometry, for percent protein monomer with use of high-performance size-exclusion chromatography, and for in vitro clot lysis activity. RESULTS: In the control samples, optical clarity was clear or colorless in all samples; protein concentration was 1.02 mg/mL +/- 0; protein monomer was 98%; and clot lysis activity was 108% per mg +/- 1. In the test samples, optical clarity was clear or colorless in all samples; protein concentrations at 0.5, 3, and 6 minutes were 0.98 mg/mL +/- 0.02, 0.93 mg/mL +/- 0.01, and 0.86 mg/mL +/- 0.02, respectively, at 1 W, and 1.00 mg/mL +/- 0.03, 0.94 mg/mL +/- 0.10, and 0.84 mg/mL +/- 0.17, respectively, at 2 W. Protein monomer was 98% for all samples. Clot lysis activity levels at 0.5, 3, and 6 minutes were 111% per mg +/- 1, 110% per mg +/- 1, and 115% per mg +/- 1, respectively, at 1 W, and 110% per mg +/- 0, 111% per mg +/- 1, and 116% per mg +/- 2, respectively, at 2 W. CONCLUSIONS: Alteplase solutions exposed to low-power US energy for as long as 6 minutes remained fully active and stable as determined by protein assays. Further investigation is warranted with use of combinations of US energy and alteplase.

Biological Assay↗
PubMed2005

Alteplase as a catheter locking solution: in vitro evaluation of biochemical stability and antimicrobial properties.

PURPOSE: To reduce potential complications of fibrin deposition to catheter surfaces, there is increasing empiric use of alteplase as a catheter lock solution. The purpose is to evaluate the properties of alteplase when reconstituted in sterile water (SW) or bacteriostatic water (BW) for prolonged periods. MATERIALS AND METHODS: Alteplase in glass vials was reconstituted (1 mg/mL) with SW or BW (0.9% benzyl alcohol) in duplicates and stored at 37 degrees C. Biochemical assays were performed at days 0 and 7 and included optical clarity, protein concentration, percent protein monomer, and in vitro clot lysis activity. Microbiologic assays were performed on days 7 through 28 with use of a standardized antimicrobial effectiveness test (pass/fail) and pour-plate methods incubated at 22.5 degrees C (fungus, 3-7 days) or 32.5 degrees C (bacteria, 3-5 days). Organisms tested included Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Aspergillus niger. RESULTS: Biochemical assay results were as follows: on day 0, all samples were clear/colorless; protein concentrations were 1.10 mg/mL +/- 0 in SW and 1.11 mg/mL +/- 0 in BW; percent protein monomer was 8.2% +/- 0.07 in SW and 98.6% +/- 0.07 in BW; and in vitro clot lysis activity (in percent of relative activity) was 100% in all samples. On day 7, all samples were clear/colorless, protein concentrations were 1.11 mg/mL +/- 0.07 in SW and 1.11 mg/mL +/- 0.07 in BW; percent protein monomer was 97.4% +/- 0.21 in SW and 96.1% +/- 0.21 in BW; and in vitro clot lysis activity (relative activity compared with day 0) was 91% +/- 2.8 in SW and 90% +/- 2.8 in BW. Microbiologic assays (US Pharmacopeia [USP] antimicrobial effectiveness test) yielded a failing result for alteplase reconstituted in SW and a passing result for alteplase reconstituted in BW. CONCLUSIONS: Alteplase reconstituted with SW or BW remains relatively stable with retained bioactivity when stored at 37 degrees C for as long as 7 days. Despite the biochemical similarities of the two solutions, only alteplase in BW met USP criteria as an effective antimicrobial solution. Further clinical evaluation is warranted.

Biological Assay↗
PubMed2005

Characterization of alteplase (tPA) following delivery through the AngioJet rheolytic catheter.

PURPOSE: To analyze alteplase solutions following delivery through the AngioJet Xpeedior rheolytic thrombectomy device to characterize the viability of proteins exposed to high shear stress. METHODS: Alteplase solutions were prepared by reconstitution in sterile water to obtain a targeted concentration of 1.0 mg/mL. A baseline control sample was obtained. The AngioJet system was modified by occluding the return line to allow collection of the dispersed fluid volume. Alteplase solutions (n=5) were delivered through the 6-F, 120-cm Xpeedior catheter and collected. All samples were assayed and compared to baseline using qualitative visual inspection, ultraviolet spectrophotometry, size exclusion chromatography, and in vitro clot lysis assays. RESULTS: Analysis of the test solutions demonstrated a mean protein recovery of 98.0%+/-3.5% of targeted concentration; the collected protein was fully active, as determined by clot lysis assays (specific activity > or =100%). All samples were clear and colorless. No significant fragmentation or aggregation of protein was observed. CONCLUSIONS: Alteplase solutions, when delivered through the AngioJet Xpeedior rheolytic thrombectomy device, remain stable and biologically active in vitro. Further clinical investigation is warranted using this method as a novel approach for pharmacomechanical thrombolysis.

Catheterization↗
PubMed2004

Thrombolysis for lower extremity deep venous thrombosis.

Catheter-directed thrombolysis (CDT) has been proposed as an alternative mode of therapy to anticoagulation in patients with massive, symptomatic deep vein thrombosis of the extremity. The major goal of therapy is to rapidly restore venous blood flow, reduce the pain and edema of the extremity, preserve venous valve function, and reduce chronic symptoms related to chronic venous hypertension (postthrombotic syndrome). In patients with iliofemoral deep venous thrombosis (DVT) standard angiographic techniques are used to instrument a lower extremity vein (popliteal) and venography is performed followed by catheter-directed infusion of a plasminogen activator directly into the thrombus. Following lytic infusion, the interventionalist must evaluate the venous drainage to determine if there is an anatomic lesion that requires further endovascular treatment (eg, iliac vein compression syndrome). Posttreatment therapy usually consists of warfarin therapy and venous compression stockings for at least 3 to 6 months. The purpose of this article is to review the technical approach used in treating iliofemoral DVT and highlight the hurdles that face interventionalists in attempting to broaden this procedure to most types of lower extremity DVT.

Catheterization, Peripheral↗
PubMed2004

TIPS reduction with use of stents or stent-grafts.

This report describes new techniques to perform TIPS reduction in patients with post-TIPS complications. Methods included hourglass-shaped stents and stent-grafts, and parallel stents and stent-grafts. All procedures were technically successful, resulting in increased portosystemic gradients and decreased symptoms, although patient outcomes were mixed. None of the patients experienced recurrent variceal hemorrhage or ascites in short-term follow-up. Stent-grafts have the advantage of immediate exclusion of blood flow outside the reducing stent, resulting in an immediate reduction of the caliber of the shunt. Techniques that allow fine adjustment of shunt diameters may have further advantages.

Aged↗
PubMed2004

Alteplase for treatment of occluded peripherally inserted central catheters: safety and efficacy in 240 patients.

PURPOSE: Peripherally inserted central catheters (PICCs) have dramatically improved intravenous therapy, but thrombotic occlusion remains a common problem. Despite the popularity of PICCs, there are few prospective data on the use of fibrinolytic agents to salvage these particular devices. The purpose of this study was to evaluate the efficacy and safety of alteplase treatment. MATERIALS AND METHODS: A subgroup analysis was performed from a phase IIIB prospective, multicenter trial of 995 patients evaluating the use of alteplase to restore function in occluded venous catheters. Two hundred forty patients (126 men; mean age, 53.5 years; range, 2-90 y) with occluded single-lumen (n = 104) or double-lumen (n = 136) PICCs were identified and constitute the study population. Dysfunction was defined as the inability to withdraw 3 mL of blood. Alteplase (2 mg/2 mL) was instilled into the dysfunctional lumen and assessed at 30 and 120 minutes. If the lumen remained occluded, a second alteplase dose was instilled and assessed at 30 and 120 minutes. Patency was defined as the ability to withdraw 3 mL blood and infuse 5 mL of saline solution. The primary efficacy endpoint was the cumulative restored patency rate after a maximum of two doses of alteplase. The primary safety endpoint was the incidence of intracranial hemorrhage within 5 days of treatment. Serious adverse events were recorded for 30 days after treatment. RESULTS: The primary efficacy endpoint was 92.9% (95% CI: 88.8%, 95.8%). Cumulative efficacy 30 and 120 minutes after first and second doses were 59.4%, 81.1%, 89.1%, and 92.9%, respectively. The primary safety endpoint was 0.0%. One major hemorrhage was reported: a patient with acute flare of ulcerative colitis experienced hematochezia 3 days after treatment. One serious adverse event (fever) was attributed to study drug. CONCLUSIONS: Treatment with use of a maximum of two doses of alteplase is safe and effective in restoring function to occluded PICCs.

Adult↗
PubMed2003

The safety, efficacy, and pharmacoeconomics of low-dose alteplase compared with urokinase for catheter-directed thrombolysis of arterial and venous occlusions.

PURPOSE: The purpose of this study was to compare the efficacy, complications, and costs associated with low-dose (<2 mg/h) alteplase (tissue plasminogen activator [t-PA]) versus urokinase for the catheter-directed treatment of acute peripheral arterial occlusive disease (PAO) and deep vein thrombosis (DVT). MATERIALS AND METHODS: A retrospective review was performed during sequential time periods on two groups with involved extremities treated with either t-PA with subtherapeutic heparin (TPA group) or urokinase with full heparin (UK group) at a single center. Treatment group characteristics, success rates, complications, dosages, infusion time, and costs were compared. RESULTS: Eighty-nine patients with 93 involved limbs underwent treatment (54 with DVT, 39 with PAO). The treatment groups were statistically identical (TPA: 45 limbs; 24 with DVT, 53.3%; 21 with PAO, 46.7%; UK: 48 limbs; 30 with DVT, 62.5%; 18 with PAO, 37.5%). The overall average hourly infused dose, total dose, infusion time, success rates, and cost of thrombolytic agent were as follows (+/- standard deviation): TPA, 0.86 +/- 0.50 mg/h, 21.2 +/- 15.1 mg, 24.6 +/- 11.2 hours, 89.4%, $466 +/- $331; and UK, 13.5 +/- 5.6 (10(4)) U/h, 4.485 +/- 2.394 million U, 33.3 +/- 13.3 hours, 85.7%, $6871 +/- $3667, respectively. Major and minor complication rates were: TPA, 2.2% and 8.9%; and UK, 2.1% and 10.4%, respectively. No statistical differences in success rates or complications were observed; however, t-PA was significantly (P <.05) less expensive and faster than urokinase. CONCLUSION: Low-dose t-PA combined with subtherapeutic heparin is equally efficacious and safe compared with urokinase. Infusions with t-PA were significantly shorter and less expensive than those with urokinase.

Adult↗
PubMed2003

Recombinant tissue plasminogen activator (alteplase) for restoration of function to occluded central venous catheters in pediatric patients.

PURPOSE: To evaluate the safety and efficacy of alteplase for restoring function to occluded central venous catheters in a pediatric population. PATIENTS AND METHODS: A phase III, open-label, single-arm, multicenter trial was performed in 995 adult and pediatric patients with dysfunctional nondialysis catheters and ports. This report is a subset analysis of subjects between 2 and 18 years of age (N = 122) who were enrolled in the study. Alteplase (2 mg/2 mL) was instilled into the dysfunctional catheter lumen and assessed at 30 and 120 minutes. Subjects weighing > or =30 kg received 2 mL of alteplase; subjects <30 kg received 110% of the internal lumen volume (not exceeding 2 mL). Alteplase dosing was repeated once after 120 minutes if the catheter remained dysfunctional. The primary safety endpoint was the rate of intracranial hemorrhage (ICH) within 5 days of treatment. RESULTS: The overall efficacy following up to two instilled doses of alteplase was 87%. In 70 patients (57%), restoration of catheter flow occurred by 30 minutes following a single dose of alteplase. Restoration of function was related to the duration of occlusion (P = 0.04). For catheters with occlusions of 0, 1 to 14, and >14 days duration, the efficacy was 91%, 78%, and 60%, respectively. Success was independent of the patient's age, sex, body weight, CVC type, or catheter age. There were no cases of death, ICH, major bleeding episodes, or embolic events attributable to treatment. CONCLUSIONS: An alteplase regimen of up to two 2-mg doses is safe and effective for restoration of function to occluded central venous catheters in a pediatric population.

Adolescent↗
PubMed2003

Alteplase: stability and bioactivity after dilution in normal saline solution.

PURPOSE: To characterize the biochemical stability and bioactivity of reconstituted alteplase when diluted to a concentration of 0.01 mg/mL in normal saline solution and stored at ambient temperature for as long as 24 hours in commercial saline solution bags. MATERIALS AND METHODS: Two commercially available formulations of lyophilized alteplase (2-mg and 50-mg vials, respectively) were reconstituted with sterile water to a final concentration of 1 mg/mL. For each vial configuration, 5 mg of alteplase (5 mL) was added to a commercial 500-mL bag of normal saline solution to achieve a 0.01-mg/mL targeted concentration. Solutions were assayed for optical clarity, pH, protein concentration, and in-vitro clot lysis activity. Assays of the solutions were performed at time points of 0 (control), 4, 8, and 24 hours at ambient room temperature and compared to controls. RESULTS: On visual inspection, aliquots of the diluted protein solutions in clear glass vials remained clear/colorless after 24 hours. Bioactivity (clot lysis assay) over the course of 24 hours at ambient temperature remained essentially unchanged relative to control (2-mg vial: mean of 98.3%, range of 93.7%-103.3%; 50-mg vial: mean of 103.1%, range of 100.6%-108.3%). The mean protein recovery rates (relative to targeted concentration) over a 24-hour period were 43% (range, 39%-46%) and 42% (range, 40%-45%) for the 2-mg and 50-mg vial configurations, respectively. CONCLUSIONS: Alteplase diluted in normal saline solution at a concentration of 0.01 mg/mL is biochemically stable and active at ambient temperature for as long as 24 hours as assessed by in vitro clot lysis assays. Alteplase appears to have a bimodal solubility profile in normal saline solution and further studies are required to determine the activity and solubility of alteplase concentrations lower than 0.01 mg/mL.

Biological Assay↗
PubMed2003

Tenecteplase: stability and bioactivity of thawed or diluted solutions used in peripheral thrombolysis.

PURPOSE: Tenecteplase (TNK; TNKase) is a third-generation plasminogen activator approved for acute myocardial infarction with an enhanced safety profile compared to alteplase. The stability and bioactivity of reconstituted frozen/thawed and diluted tenecteplase solutions used in noncoronary peripheral thrombolysis was determined. MATERIALS AND METHODS: Lyophilized TNK was freshly reconstituted in sterile water (5 mg/mL) and used as control. In freeze/thaw studies, reconstituted TNK aliquots were stored frozen for 4 weeks at -20 degrees C, thawed at ambient temperature, and assayed with and without an additional freeze/thaw cycle. Additional freshly reconstituted TNK aliquots were assayed after six freeze/thaw cycles when frozen at two separate temperatures (-20 degrees and -70 degrees C) and thawed at 2-8 degrees C or ambient temperature. In dilution studies, reconstituted TNK was diluted in 500-mL commercially available normal saline solution bags to concentrations of 0.01, 0.02, and 0.05 mg/mL. Samples were assayed after 0, 8, and 24 hours at ambient temperature. Optical clarity, pH, protein concentration, particle counts, and in-vitro clot-lysis assays were performed. Protein monomer (%), single-chain protein (%), and particle counts were performed in freeze/thaw studies. RESULTS: Frozen/thawed TNK aliquots met all specifications as freshly reconstituted product. For dilution studies (0.01, 0.02, and 0.05 mg/mL), the recovered protein retained 83%-100% bioactivity after 24 hours. The recovered protein rates over the course of 24 hours (relative to target concentration) were 70%-75%, 80%-85%, and 94%-95% at 0.01, 0.02, and 0.05 mg/mL, respectively. Assayed solutions were clear/colorless at all concentrations and time points. CONCLUSION: TNK is fully active after reconstitution and freezing/thawing. TNK dilutions used in clinical practice (0.01-0.05 mg/mL) demonstrated retention of biologic activity at 24 hours without precipitates.

Biological Assay↗
PubMed2002

Safety and efficacy of alteplase for restoring function in occluded central venous catheters: results of the cardiovascular thrombolytic to open occluded lines trial.

PURPOSE: To evaluate the safety and efficacy of alteplase (TPA) for restoring function to occluded central venous catheters (CVCs). PATIENTS AND METHODS: The study design was a phase III, open-label, single-arm multicenter trial. Subjects with occluded, nondialysis CVCs were enrolled. All subjects received a 2-mg dose of TPA within the dysfunctional catheter lumen that was allowed to dwell for 30 to 120 minutes. Functionality was tested at 30 and 120 minutes. If the CVC remained obstructed at 120 minutes, a second 2-mg TPA dose was allowed to dwell for 30 to 120 minutes. The primary safety end point was the rate of intracranial hemorrhage (ICH) within 5 days of treatment, and serious adverse events were recorded up to 30 days. RESULTS: Nine hundred ninety-five patients received treatment (female, 562; male, 433; mean age, 50.7 years; range, 2 to 91 years). CVCs treated were as follows: single (26%), double (39%), or triple (6%) lumen catheters or ports (29%). The primary end point was 0% ICH within 5 days. There were no cases of death, major bleeding episodes, or embolic events attributable to treatment. Flow was successfully restored in 52% and 78% of CVCs at 30 and 120 minutes after one dose, and 84% and 87% at 30 and 120 minutes after a second dose, respectively. Restoration of flow was 86%, 93%, 90%, and 79%, for single, double, and triple lumen catheters and ports, respectively. Estimated 30-day catheter patency was 74%. CONCLUSION: A regimen of up to two 2-mg doses of TPA is safe and effective for the restoration of flow to occluded central venous catheters.

Adolescent↗
PubMed2002

Central venous catheters in home infusion care: outcomes analysis in 50,470 patients.

PURPOSE: Outpatient home infusion therapy is increasing; however, little data exist on the outcomes of patients receiving care. The purpose of this study was to document the natural history of central venous catheters (CVCs) used in home infusion care to determine the rate and type of catheter complications. MATERIALS AND METHODS: Data from the Strategic HealthCare Programs National Database from April 1999 to September 2000 were analyzed. Primary study objectives were to identify (i) types of CVCs and principal diagnoses, (ii) type and rate of catheter complications, and (iii) outcomes in managing thrombotic catheter complications. Event rates were calculated per 1,000 catheter days; 50,470 patients representing 2.83 million catheter days met study criteria. RESULTS: The rates of complications (per 1,000 catheter days) for the most common events were: catheter dysfunction (0.83 total; 0.6 nonthrombotic, 0.23 thrombotic), catheter site infections (0.26), and bloodstream infections (BSIs; 0.19). A total of 4,138 complication events were identified (event rate per 1,000 days: 1.5). The total rates of complications with each catheter type were: midline catheters (4.5), PICCs (2.0), nontunneled central catheters (1.1), tunneled catheters (1.0), and chest ports (0.52). Catheter dysfunction with loss of patency was the most common group of complications. Thrombotic occlusion was the principal cause of catheter dysfunction, occurring in 28% of patients in this group, typically within 7 days of catheter insertion. BSI was reported in 541 patients, generally more than 30 days after catheter insertion. Catheter thrombosis outcomes resulted in therapy interruption (43%), catheter replacement (29%), premature CVC removal (14%), unscheduled emergency room visits (9%), and/or hospitalizations (6%). CONCLUSION: Catheter dysfunction is the most frequent complication of all CVCs in this population, almost twice that of infections. Outpatient home infusion catheter dysfunction results in delays to therapy, unscheduled hospitalizations, and need for device replacement.

Adolescent↗
PubMed2002

Treatment of occluded central venous catheters with alteplase: results in 1,064 patients.

PURPOSE: Thrombosis of central venous access devices (CVADs) is a relatively frequent complication. Alteplase (tissue plasminogen activator) has been used to salvage dysfunctional devices. The purpose of this study was to analyze the safety and efficacy of alteplase after administration of a maximum of two 2-mg/2-mL doses to thrombosed CVADs. MATERIALS AND METHODS: A combined analysis was performed of two pivotal prospective phase-III clinical trials (Cardiovascular thrombolytic to Open Occluded Lines [COOL] Trials) involving 80 centers enrolling patients from November 1999 through December 2000. Patients 2 years of age or older (with body weights >10 kg) with dysfunctional nondialysis CVADs were eligible, including those with peripherally inserted central catheters, apheresis catheters, and ports. Alteplase (2 mg/2 mL) was instilled into the lumen of the central venous catheter and allowed to dwell for as long as 120 minutes. For patients with body weights of 10-30 kg, 110% of the internal lumen volume of alteplase (2 mg/2 mL) was administered. If the device was still occluded after a maximum of 120 minutes, a second alteplase dose was given and allowed to dwell for as long as 120 minutes. The primary efficacy endpoint was designated as restored function after a maximum of two doses. The primary safety endpoint was intracranial hemorrhage (ICH) within 5 days. RESULTS: A total of 1,064 patients (465 men, 599 women; mean age, 50.7 y; range, 2-91 y) with dysfunctional catheters were treated. After alteplase administration, function was restored in 798 patients (75.0%; 95% CI: 72.3%, 77.6%) after one dose and 905 (85.1%; 95% CI: 82.8%, 87.2%) after two doses. Efficacy rates were similar among catheter types (single-, double-, and triple-lumen catheters, and ports). Serious adverse events monitored within 30 days of treatment included ICH (0.0%), embolic events (0.0%), gastrointestinal bleeding (0.3%), thrombosis (0.3%), and sepsis (0.4%). One event (fever) was attributed to the study drug. Efficacy was independent of age, sex, body weight, and catheter type. CONCLUSION: A regimen of as many as two 2-mg doses of alteplase is safe and effective for restoring flow to occluded central venous access devices.

Adolescent↗
PubMed2002

Initial clinical results of tenecteplase (TNK) in catheter-directed thrombolytic therapy.

PURPOSE: To investigate the safety and immediate efficacy of 2 different doses of tenecteplase (TNK) in peripheral catheter-directed thrombolytic therapy of arterial occlusions and deep vein thrombosis (DVT). METHODS: Over a 20-month period, 63 nonconsecutive patients underwent catheter-directed thrombolytic therapy with either 0.25 mg/h or 0.50 mg/h of TNK in a nonrandomized, open-label study. Of these, 55 patients (60 limbs) were treated for DVT (36 limbs in 16 men and 15 women; mean age 41 years, range 21-73) or peripheral arterial occlusions (24 limbs in 16 men and 8 women; mean age 63 years, range 32-91). The primary endpoints were major bleeding complications and angiographic reduction in clot burden. RESULTS: The mean duration of infusion was 18 +/- 4 hours in patients with arterial occlusions and 30 +/- 13 in those with DVT. Twenty-one (87.5%) patients with occlusive disease had marked or complete lysis of clot. Thirty (83.3%) limbs with DVT had either marked or complete resolution of thrombus. There were 4 (7.3%) episodes of minor bleeding with 1 (1.8%) major hemorrhagic event. Fibrinogen levels dropped by an average of 23%. CONCLUSIONS: Preliminary evidence suggests that TNK doses of 0.25 mg/h to 0.50 mg/h appear to be safe and effective. The potential benefits of TNK therapy warrant further investigation.

Adult↗