BEUDAMED
    FDA Adverse Event Summary report: N

    THERASHERE, YTTRIUM-90 GLASS MICROSPHERES

    MDR report key: 3890647 · Received June 3, 2014

    Report

    Report Number
    3002124545-2014-00012
    Date Received
    June 3, 2014
    Date of Event
    May 22, 2014
    Report Date
    May 22, 2014
    Product Code
    KXK
    Adverse Event
    Yes
    Report Source
    Manufacturer report
    Reporter Location
    FR
    Reporter Occupation
    PHYSICIAN

    Narratives

    Additional Manufacturer Narrative · 1

    AT THE TIME OF THIS REPORT, THE EVENT OF PORTAL AND MESENTERIC VEIN THROMBOSIS, RILD WAS ONGOING. THE SUBJECT DISCONTINUED PARTICIPATION IN THE STUDY. THE INVESTIGATOR ASSESSED THE EVENT OF PORTAL AND MESENTERIC VEIN THROMBOSIS, RILD AS GRADE-3 (SEVERE) IN INTENSITY, SERIOUS DUE TO HOSPITALIZATION; AND PROBABLY RELATED TO THE STUDY DEVICE AND DEVICE PROCEDURE, DEFINITELY RELATED TO SECOND LINE CHEMOTHERAPY (FOLFIRI REGIMEN) AND ALSO RELATED TO PRE-EXISTING DISEASE (UNSPECIFIED). THE COMPANY AGREED WITH THE INVESTIGATOR'S ASSESSMENT THAT THE EVENT IS SERIOUS DUE TO HOSPITALIZATION. THE COMPANY AGREED WITH THE INVESTIGATOR'S CAUSALITY ASSESSMENT, HOWEVER, RILD WAS CONSIDERED RELATED TO STUDY DEVICE, BUT NOT TO CHEMOTHERAPY OR STUDY PROCEDURES. IT WAS ASSESSED THAT PORTAL AND MESENTERIC VEIN THROMBOSIS MIGHT BE RELATED BOTH THE STUDY DEVICE AND TO THE UNDERLYING LIVER METASTASES AND NOT RELATED TO CHEMOTHERAPY OR TO STUDY PROCEDURES. A TOTAL OF 77 SUBJECTS UNDERWENT THERASPHERE TREATMENT WHILE ENROLLED IN 3 ONGOING CLINICAL TRIALS (B)(6). THERE WERE NO REPORTS OF ADVERSE EVENTS CONSISTENT WITH A DIAGNOSIS OF PORTAL VEIN THROMBOSIS OR MESENTERIC VEIN THROMBOSIS DURING THESE TRIALS. THERE WERE 3 REPORTS OF EVENTS ASSOCIATED WITH RILD. MESENTERIC VEIN THROMBOSIS AND PORTAL VEIN THROMBOSIS: GIVEN THAT NO PRIOR REPORTS WERE RECEIVED, A RELATIONSHIP BETWEEN THE USE OF THE THERASPHERE AND THE PATIENT'S PORTAL AND MESENTERIC VEIN THROMBOSIS THE COMPANY ASSESSES AS POSSIBLY RELATED TO TREATMENT WITH THE STUDY DEVICE. THE EVENT WAS DIAGNOSED APPROXIMATELY THREE MONTHS AFTER INITIATING TREATMENT WITH THE STUDY DEVICE AND THE CAUSAL RELATIONSHIP CANNOT BE EXCLUDED. ALTERNATIVE OR CONTRIBUTING CAUSES OF THE EVENT INCLUDE DISEASE UNDER STUDY ITSELF. PORTAL VEIN THROMBOSIS OF DIFFERENT EXTENT, INCLUDING ALSO MESENTERIC VEIN, IS A KNOWN COMPLICATION OF LIVER TUMORS, BOTH PRIMARY AND SECONDARY ONES AS IT REFERENCED BY FOLLOWING ARTICLES: PIRISI M, AVELLINIC, FABRIS C, ET AL. PORTAL VEIN THROMBOSIS IN HEPATOCELLULAR CARCINOMA: AGE AND SEX DISTRIBUTION IN AN AUTOPSY STUDY. J CANCER RES CLIN ONCOL 1998; 124:397-400.K120615-023 18 REV. 10; KULIK LM, CARR B, MULCAHY MF, LEWANDOWSKI RJ ET AL. SAFETY AND EFFICACY OF 90Y RADIOTHERAPY FOR HEPATOCELLULAR CARCINOMA WITH AND WITHOUT PORTAL VEIN THROMBOSIS. HEPATOLOGY. 2008; 47(1):71-81.; SALEM R, LEWANDOWSKI R, ROBERTS C, GAIN J, ET AL. USE OF YTTRIUM-90 GLASS MICROSPHERES (THERASPHERE) FOR THE TREATMENT OF UNRESECTABLE HEPATOCELLULAR CARCINOMA IN PATIENTS WITH PORTAL VEIN THROMBOSIS. J VASE INTERV RADIOL 2004; 15:335-345. GIVEN THE PREVIOUS REPORTS FOR PATIENTS TREATED WITH THE STUDY DEVICE AND THE FACT THAT RILD IS A WELL-KNOWN COMPLICATION OF LIVER IRRADIATION, THE COMPANY ASSESSES THE EVENT AS PROBABLY RELATED TO TREATMENT WITH THERASPHERE. ADDITIONAL INFORMATION FOR THE EVENT OF PORTAL AND MESENTERIC VEIN THROMBOSIS AND RILD IS ANTICIPATED. USA - IDE: 100324 CANADA - MEDICAL DEVICE LICENSE NUMBER: 67286. DEVICE IDENTIFICATION NO. SPHERES:208651, SET: 208652, KIT: 176305. MANUFACTURER'S MEDICAL DEVICE IDENTIFIER (CATALOGUE/MODEL NO.)-ACCESSORY KIT: K125914-001, MICROSPHERE INJECTION: 990700.SPE, ADMINISTRATION SET: 990226.SPE.

    Description of Event or Problem · 1

    MANUFACTURE REPORT NUMBER: 3002124545-2014-00012; (B)(6); SAE: PORTAL AND MESENTERIC VEIN THROMBOSIS, RILD [RADIATION INDUCED LIVER DISEASE]; (MEDDRA PT: PORTAL VEIN THROMBOSIS). THIS REPORT CONCERNS SUBJECT (B)(6) -YEAR-OLD FEMALE WHO WAS ENROLLED IN STUDY (B)(6) ENTITLED "A PHASE III CLINICAL TRIAL EVALUATING THERASPHERE IN SUBJECTS WITH METASTATIC COLORECTAL CARCINOMA OF THE LIVER WHO HAVE FAILED FIRST LINE CHEMOTHERAPY". ON (B)(6) 2014, THE PATIENT RECEIVED TREATMENT WITH RANDOMIZED THERASPHERE (B)(4) ON RIGHT LOBE, (B)(4) ON LEFT LOBE FOR THE TREATMENT OF METASTATIC COLORECTAL CARCINOMA. THE SUBJECT STARTED 1ST CYCLE OF SECOND LINE CHEMOTHERAPY WITH FOLFIRI REGIMEN (IRINOTECAN 295.2 MG, FOLINIC ACID 35 MG, IV FLUOROURACIL 656MG AND FLUOROURACIL IV BOLUS TOTAL 3936MG) ON (B)(6) 2014 AND HAD RECEIVED THE 5TH CYCLE OF CHEMOTHERAPY ON (B)(6) 2014. THE SUBJECT'S RELEVANT MEDICAL HISTORY WAS NOT PROVIDED. ON (B)(6) 2014, APPROX THREE MONTHS AFTER RECEIVING TREATMENT WITH THE STUDY DEVICE AND INITIATING CHEMOTHERAPY, THE SUBJECT WAS ADMITTED TO THE HOSPITAL WITH ASTHENIA, PLEURAL EFFUSION, ASCITES, CHOLESTASIS, DECREASED PROTHROMBIN TIME AND INCREASED BILIRUBIN (VALUES UNKNOWN).ON (B)(6) 2014, A CT (COMPUTED TOMOGRAPHY) SCAN WAS PERFORMED WHICH SHOWED DISAPPEARED LIVER METASTASES WITH VERY HETEROGENEOUS LIVER STRUCTURE, SPLENOMEGALY AND PRESENCE OF NON­ VASCULARIZED THROMBOSIS OF PORTAL VEIN IN BOTH RIGHT AND LEFT BRANCH UP TO THE MESENTERIC VEIN AT CTCAE GRADE 3.

    Devices

    Seq Brand Generic Product Code Manufacturer Model Lot UDI-DI
    325187 THERASHERE, YTTRIUM-90 GLASS MICROSPHERES NONE KXK

    Patients

    Seq Age Sex Outcome Treatment
    1 65 YR Hospitalization PREDNISOLONE (CON.)| MACROGOL (CON.)| ISAPAGHUL (CON.)| ONDANSETRON (CON.)| ATROPINE (CON.)| BISOPROLOL (CON.) (TX DATE: 2009 - (B)(6) 2014)| APREPITANT (CON.)| LORAZEPAM (CON.)| PREV MEDS = UNK| CLINUTREN (CON.)| METHYLPREDNISOLONE (CON.)| CALCIUM (CON.)