***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE Central venous access devices ( CVADs ) are a mainstay of current medical therapy but often become occluded by thrombus . Tissue plasminogen activator ( alteplase ) , at a dose of 2 mg per 2 mL , has been shown to be effective in restoring flow to catheters proven by radiographic contrast injection to be occluded by thrombus . The purpose of this double-blind placebo-controlled multicenter trial was to determine the efficacy of alteplase in occluded catheters without earlier contrast injections or radiographic examinations . MATERIAL S AND METHODS Patients were eligible for inclusion if blood could not be withdrawn from their catheter after a period of normal function of at least 48 hours . Single or multiple catheters , peripherally inserted central catheters , catheters with valves , and implanted ports were eligible ; catheters used for hemodialysis were not included . Patients were r and omly assigned to one of two groups . In one group , patients received a first dose of 2 mg alteplase followed , if needed , by a second dose of 2 mg alteplase and a third dose of placebo . The other group received placebo first followed by one 2-mg dose of alteplase and then a second , if needed . Each dose was allowed to dwell for 2 hours and ability to withdraw blood from the catheter was reassessed . The endpoint was restoration of the ability to withdraw and infuse through the catheter . One hundred forty-nine patients were r and omized : 74 received placebo first , 75 received alteplase first . RESULTS After the first 2-hour treatment , function was restored to 74 % in the alteplase arm and 17 % in the placebo arm ( P < .0001 compared to placebo ) . After one or two treatments , function was restored in 90 % of patients . There were no serious study -drug-related adverse events , no intracranial hemorrhage , no major hemorrhage , and no embolic events . CONCLUSION Infusion of alteplase appeared to be safe and effective in restoring flow to occluded catheters without need for pretreatment radiographic evaluation The function of long term indwelling venous access devices is commonly perturbed by postinsertion catheter‐related complications ( CRC ) . In an effort to assess the patterns of CRC in our community accurately , a prospect i ve analysis of  Groshong catheters in adult cancer patients was undertaken PURPOSE To evaluate , in a phase III , single-arm study , the safety and efficacy of the thrombolytic agent tenecteplase in restoring function to dysfunctional central venous catheters ( CVCs ) . MATERIAL S AND METHODS Pediatric and adult patients with dysfunctional CVCs were eligible to receive as much as 2 mL ( 2 mg ) of intraluminal tenecteplase , which was left to dwell in the CVC lumen for a maximum of 120 minutes . If CVC function was not restored at 120 minutes , a second dose was instilled for an additional 120 minutes . RESULTS Tenecteplase was administered to 246 patients . Mean patient age was 44 years ( range , 0 - 92 y ) ; 72 patients ( 29 % ) were younger than 17 years of age . Chemotherapy was the most common reason for catheter insertion .  Restoration of CVC function was achieved in 177 patients ( 72 % ) within 120 minutes after the first dose . After instillation of a maximum of two doses of tenecteplase , CVC function was restored in 200 patients ( 81 % ) , with similar frequencies in pediatric ( 83 % ) and adult ( 80 % ) patients . Adverse events ( AEs ) were reported in 31 patients ( 13 % ) ; fever ( 2 % ) , neutropenia ( 1 % ) , and nausea ( 0.8 % ) were most common . One serious AE , an allergic hypersensitivity reaction , was judged to be related to tenecteplase and /or a chemotherapeutic agent that the patient was receiving concurrently . CONCLUSIONS Consecutive administration of one or two doses of tenecteplase into CVCs showed efficacy in the restoration of catheter function in patients with dysfunctional CVCs PURPOSE This study was undertaken to determine the role of low-dose urokinase infusions in treating fibrinous occlusions of venous access devices ( VADs ) in cancer patients . PATIENTS AND METHODS Forty-two patients with VAD occlusions refractory to routine urokinase instillations were documented by x-ray ( cathetergram ) to have fibrin sleeves at the catheter tips . They were r and omized to receive infusions of either urokinase ( 40,000 U/h ) or urokinase with heparin ( 320 U/h ) through their catheters . After 1 , 3 , 6 , and 12 hours of treatment , the function of the VADs was reassessed . Whenever the obstruction had been relieved , the infusion was stopped and a repeat cathetergram was performed . The status of the unoccluded catheters was followed to determine the longevity of the restored function . RESULTS Twenty-one catheters were treated with urokinase alone and 21 with the combination of urokinase and heparin . In each group , 16 VADs opened within 12 hours of treatment and five did not . By actuarial analysis , the probability was only 0.28 that a reopened catheter would reocclude within 6 months . CONCLUSION Low-dose urokinase infusions can restore function to the majority of catheters occluded by fibrin sleeves . Adding heparin to the urokinase does not enhance the efficacy of the infusions . The restored function often persists until the VADs are removed PURPOSE Recombinant urokinase ( r-UK ) is a high-molecular-weight urokinase produced in transfected , non-human , mammalian cells . A Phase II , r and omized , double-blind , parallel , placebo-controlled , dose-ranging study was performed to compare the safety and efficacy of one or two instillations of three intraluminal concentrations of r-UK ( 5,000 ; 15,000 ; and 25,000 IU/mL ) with a placebo for reestablishment of total function to occluded central venous access devices ( CVADs ) . MATERIAL S AND METHODS One-hundred eight patients with CVAD withdrawal or total occlusion were enrolled and r and omized to treatment ; 104 patients received at least one instillation of study drug and 101 patients completed treatment . All but one patient had cancer . RESULTS All three concentrations of r-UK were significantly superior to placebo in restoring total CVAD function ( patency of all occluded lumens ) after one or two instillations of study medication ( 25,000 IU/mL r-UK , 68 % vs. placebo , 28 % [ P = .007 ] ; 15,000 IU/mL r-UK , 69 % vs. placebo , 24 % [ P = .004 ] ; 5,000 IU/mL r-UK , 70 % vs. placebo , 28 % [ P = .003 ] ) . Comparisons of the three r-UK concentrations indicated no difference after one or two instillations with regards to patency restoration . Treatment-emergent hemorrhagic events occurring within 72 hours after study drug exposure were experienced by four patients ( 17 % ) in the 25,000 IU/mL r-UK group , two patients ( 7 % ) in the 15,000 IU/mL r-UK group , no patients in the 5,000 IU/mL r-UK group , and no patients in the placebo group . CONCLUSIONS Efficacy and safety results of this study support further evaluation of a 5,000 IU/mL concentration of r-UK for treatment of occluded CVADs in adult and pediatric patients from 1 year of age PURPOSE To evaluate the incidence and management of catheter occlusion in implantable arm ports . MATERIAL S AND METHODS Findings were prospect ively examined in 391 patients in whom 393 arm ports were placed . The indications for port placement included chemotherapy ( n = 347 ) , antibiotic administration ( n = 35 ) , combination chemotherapy/antibiotic use ( n = 7 ) , transfusion ( n = 3 ) , and phlebotomy ( n = 1 ) . Of the total catheters , 323 ( 82.2 % ) underwent tip modification prior to placement . Malfunctioning catheters were usually treated with urokinase instillation . RESULTS Three hundred ninety-three devices were implanted with 247 mean days of catheter use ( total , 97,256 days ; range , 1 - 694 days ) . The overall incidence of catheter occlusion was 0.14 per 100 catheter days . A single catheter occlusion occurred in 90 ( 22.9 % ) catheters , with a mean of 90.1 days before the event . A second occlusion occurred in 36 ( 9.2 % ) of the above catheters , with a mean of 60.1 catheter days before the second event . Eighty-five ( 24.0 % ) of the 347 cancer patients had at least one occlusive event , yielding a complication rate of 0.098 per 100 catheter days at risk ( 95 % confidence interval [ CI ] ; 0.079 - 0.114 ) . Of the 35 patients receiving antibiotics  , three ( 8.6 % ) had at least one occlusive event . This represented a complication rate of 0.032 per 100 catheter days at risk ( 95 % CI ; 0.010 - 0.061 ) . Seventeen ( 24.3 % ) of the nonmodified catheters developed an occlusion versus 72 ( 22.3 % ) of the modified ( P > .05 ; Fisher exact test ) . Of the catheters with a first occlusive event , 75 ( 98.7 % ) were treated successfully with urokinase instillation . Four ( 1.0 % ) patients developed symptomatic subclavian vein thrombosis . No bleeding complications occurred . CONCLUSION Catheter occlusion is a common complication of long-term arm port placement , with a significantly higher incidence in the cancer patients in our series ( P < . 05 , Fisher exact test ) . Catheter tip modification , however , does not considerably affect the incidence of occlusion .  Low-dose urokinase therapy is a safe and efficacious treatment of catheter occlusion , obviating the need for catheter removal PURPOSE Alfimeprase is a recombinantly produced , genetically modified variant of the metalloproteinase , fibrolase . Alfimeprase proteolytically cleaves fibrin , independent of plasminogen activation to plasmin , and directly dissolves thrombi . Based on the direct fibrin degradation effect of alfimeprase , rapid activity in patients with occluded central venous access devices ( CVADs ) was hypothesized . PATIENTS AND METHODS We performed a phase II , r and omized , double-blind , active-control , multicenter , dose-ranging study to compare the safety and efficacy of one or two instillations of three intraluminal doses of alfimeprase ( 0.3 , 1.0 , and 3.0 mg ) and alteplase 2.0 mg in re-establishing patency to occluded CVADs in 55 adult patients . RESULTS All three alfimeprase doses were more successful than alteplase during the first 15 and 30 minutes of treatment . The alfimeprase 3.0-mg dose result ed in 40 % , 50 % , and 60 % patency restoration rates at 5 , 15 , and 30 minutes , respectively , compared with 0 % , 0 % , and 23 % for alteplase . The difference at 15 minutes was highly significant ( P = .0075 ) . Alfimeprase 3.0 mg produced the highest patency rate at 120 minutes after the first ( 60 % ) and second ( 80 % ) doses . No major hemorrhagic or embolic events were reported . CONCLUSION A single 1- or 3-mg dose of alfimeprase has the potential to restore function to occluded CVADs rapidly and safely , and to facilitate on-time infusion of vital therapies PURPOSE To evaluate the efficacy and safety of reteplase for central venous catheter ( CVC ) occlusion in patients with cancer . MATERIAL S AND METHODS An open-label , single-arm , prospect i ve study was conducted . Reteplase ( 0.4 U ) was instilled into each catheter lumen with a dwell time of 30 minutes in patients with cancer with a dysfunctional CVC . If the function of the catheter was not restored in 30 minutes , an additional dwell time of 30 minutes was allowed ( a total of 60 minutes possible dwell time for the first dose ) . A second dose was repeated at 60 minutes after the first dose if catheter function was not restored ( a total of 120 minutes for up to two doses ) . The primary efficacy outcome was the restoration of CVC function . RESULTS Of 139 patients who received reteplase , the first-attempt success rate after a 30-minute dwell time was 66.9 % 
    Output:
    
Conclusion The most common interventions used to treat thrombotic catheter occlusion in cancer patients  were urokinase and alteplase .