MAUDE Adverse Event Report: BIOCOMPATIBLES UK LTD THERASPHERE; YTTRIUM-90 GLASS MICROSPHERES, PRODUCT CODE: NAW

Model Number UNKNOWN

Device Problem Adverse Event Without Identified Device or Use Problem (2993)

Patient Problems Abdominal Pain (1685); Anemia (1706); Diarrhea (1811); Dysphagia/ Odynophagia (1815); Edema (1820); Fever (1858); Hair Loss (1877); Hearing Impairment (1881); Inflammation (1932); Nausea (1970); Pain (1994); Rash (2033); Local Reaction (2035); Renal Failure (2041); Swollen Lymph Nodes (2093); Thrombosis (2100); Vomiting (2144); Malaise (2359); Fungal Infection (2419); Weight Changes (2607); Test Result (2695); No Code Available (3191); Constipation (3274)

Event Type  Injury  

Manufacturer Narrative

Btg medical assessment: this is a phase ii study, conducted with the aim of demonstrating the benefit of the association of therasphere and chemotherapy in patient with intra hepatic cholangiocarcinoma, which is a labelled use for therasphere 41 patients were included in the study, 26 (63%) were male with a mead age of 64 years.The trial was conducted in 7 centres in france from november 12, 2013 through june 21, 2016.Eligible patients were aged 18 years or older, had unresectable icc, a measurable lesion (>2 cm), either non-cirrhotic liver or cirrhosis with child-pugh score less than b8 (a score of liver function in which lower scores indicate better liver function), eastern cooperative oncology group performance status of 0 or 1, no or limited extrahepatic disease (limited extrahepatic disease was defined as hilar lymph node <3 cm or <5 lung nodules, each <10 mm), adequate hematologic or kidney function, albumin level of at least 28 g/l (to convert to milligrams per decilitre, divide by 10), and bilirubin level less than or equal to 3 times the upper limit of normal.Procedure: after inclusion, patients-initiated chemotherapy with the gemcitabine plus cisplatin regimen.In case of 1 hemi liver involvement, the sirt was performed during cycle 1 (days 3-21); in case of involvement of both hemi livers, a first sirt was performed as described previously and a second sirt procedure was done during cycle 3 (days 3-21) to cover both hemi livers.In case of anatomic variants of liver arteries, up to 3 sirt sessions were allowed at the discretion of the interventional radiologists.Chemotherapy was continued for a recommended number of 6 cycles, but prolongation of chemotherapy (biweekly gemcitabine plus cisplatin or gemcitabine alone) was accepted when deemed to be necessary by the investigators.The gemcitabine plus cisplalin regimen consisted of cisplatin, 25mg/m2, administered on days 1 and 8 and gemcitabine, 1000 mg/m2, administered on days 1 and 8, with cycles repeated every 3 weeks.For the cycle concomitant and the cycle after sirt, the gemcitabine dose was decreased to 300mg/m2 because of concerns about potential toxic effects from the combination with sirt.Selective internal radiotherapy (sirt) was performed 8 to 15 days later and the second angiography using glass microspheres.Activity administered was calculated with the aim of administering a dose of 120 gy (within 20-gy range) to the targeted liver volume (injected hemiliver) without exceeding a cumulative does of 50 gy to the lungs.Clinical and biological evaluation were performed at d1, d7 of each cycle of chemotherapy the paper discussed adverse events as follows: twenty-nine patients (71%) experienced grade 3 or 4 toxic effects.More liver toxic effects occurred in the 12 patients with cirrhosis than in the patients without cirrhosis.Among patients with cirrhosis treated with sirt without chemotherapy, 9 of 12 patients (75%) experienced hepatic failure (all grade ascites or jaundice with 5 non-reversible cases vs 5 of 29 patients (17%) without cirrhosis (all reversible cases) (p=.001).In all cases of non-reversible toxic effects, patients had received whole-liver sirt.There is no restriction for the use of therasphere in patients that have received or will receive chemotherapy before and/or after therasphere administration.Btg medical assessment: serious/unknown adverse events: nausea (grade 3) 2 patients; related to chemotherapy agent; anticipated with chemo drug abdrominal pain (grade 3); possibly related to device; anticipated event vomiting (grade 3); related to chemotherapy agent; anticipated with chemo drug diarrhoea (grade 3: related to chemotherapy agent; anticipated with chemo drug neutropenia (grade 3) related to chemotherapy agent; anticipated with chemo drug febrile neutropenia (grade 3): related to chemotherapy agent; anticipated with chemo drug anaemia (grade 3): related to chemotherapy agent; anticipated with chemo drug thrombocytopenia (grade 3): related to chemotherapy agent; anticipated with chemo drug lymphoneia (grade 3): possibly related to device and chemotharapy associated; anticipated event cholecystitis acute (grade 3): possibly related to device; anticipated adverse event cholangitis (grade 3): concomitant disease venous thrombosis (grade 3): concomitant disease decreased appetite (grade 3): possibly related to device; anticipated event weight decreased (grade 3): concomitant disease general physical health deterioration (grade 3): possibly related device; anticipated event non-serious adverse events: rash: related to chemotherapy/contrast product alopecia: related to chemotherapy palmar-planatar erythrodysaesthesia syndrome: related to chemotherapy hypoacousia/hpyeracousia: related to chemotherapy renal failure: related to chemotherapy peripheral sensorimotor neuropath: related to chemotherapy taste altheration: related to chemotherapy nausea (grade 1/2): related to chemotherapy abdominal pain (grade 1/2): possibly related device; anticipated event vomiting (grade 1/2): related to chemotherapy diarrhoea (grade 1/2): related to chemotherapy dysphagia: concomitant disease constipation: concomitant disease neutropenia (grade 1/2) related to chemotherapy anaemia (grade 1/2): related to chemotherapy thrombocytopenia (grade 1/2): related to chemotherapy lymphopenia (grade 1/2): possibly related to device and chemotherapy associated; anticipated event cholyecystitis acute (grade 1/2): possibly device; anticipated epistaxis (grade 1/2): concomitant disease venous thrombosis (grade 1/2): concomitant disease oral fungal infection (grade 1/2): related to chemotherapy decreased appetite (grade 1/2): possible related device; anticipated event weight decreased (grade 1/2): concomitant disease pain (grade 1/2): possibly related device and chemotherapy associated; anticipated event mucosal inflammation (grade 1/2): related to chemotherapy edema (grade 1/2): concomitant disease administration site reaction (grade 1/2): related to device; anticipated event no batch review was possible for this case as the batch number(s) could not be ascertained and the product was not returned for evaluation (devices remain implanted in the patients and information was obtained via a literature review).No product malfunction/deficiency has been identified or reported.No corrective/preventative action has been identified.Should we receive any information to enable further investigations, a follow-up report will be submitted.At this time this report is considered final.

Event Description

Review of literature article: radio embolization plus chemotherapy for first-line treatment of locally advanced intrahepatic cholangiocarcinoma a phase 2 clinical trial - author: julien edeline et al 41 patients were included in the study, 26 (63%) were male with a mead age of 64 years.The trail was conducted in 7 centres in france from november 12, 2013 through june 21, 2016.Eligible patients were aged 18 years or older, had unresectable icc, a measurable lesion (>2 cm), either noncirrhotic liver or cirrhosis with child-pugh score less than b8 (a score of liver function in which lower scores indicate better liver function), eastern cooperative oncology group performance status of 0 or 1, no or limited extrahepatic disease (limited extrahepatic disease was defined as hilar lymph node <3 cm or <5 lung nodules, each <10 mm), adequate hematologic or kidney function, albumin level of at least 28 g/l (to convert to milligrams per decilitre, divide by 10), and bilirubin level less than or equal to 3 times the upper limit of normal.Procedure: after inclusion, patients-initiated chemotherapy with the gemcitabine plus cisplatin regimen.In case of 1 hemi liver involvement, the sirt was performed during cycle 1 (days 3-21); in case of involvement of both hemi livers, a first sirt was performed as described previously and a second sirt procedure was done during cycle 3 (days 3-21) to cover both hemi livers.In case of anatomic variants of liver arteries, up to 3 sirt sessions were allowed at the discretion of the interventional radiologists.Chemotherapy was continued for a recommended number of 6 cycles, but prolongation of chemotherapy (biweekly gemcitabine plus cisplatin or gemcitabine alone) was accepted when deemed to be necessary by the investigators.The gemcitabine plus cisplatin regimen consisted of cisplatin, 25mg/m2, administered on days 1 and 8 and gemcitabine, 1000 mg/m2, administered on days 1 and 8, with cycles repeated every 3weeks.For the cycle concomitant and the cycle after sirt, the gemcitabine dose was decreased to 300mg/m2 because of concerns about potential toxic effects from the combination with sirt.Selective internal radiotherapy (sirt) was performed 8 to 15 days later and the second angiography using glass microspheres.Activity administered was calculated with the aim of administering a dose of 120 gy (within 20-gy range) to the targeted liver volume (injected hemiliver) without exceeding a cumulative does of 50 gy to the lungs.The paper discussed adverse events as follows: twenty-nine patients (71%) experienced grade 3 or 4 toxic effects.More liver toxic effects occurred in the 12 patients with cirrhosis than in the patients without cirrhosis.Among patients with cirrhosis treated with sirt without chemotherapy, 9 of 12 patients (75%) experienced hepatic failure (all grade ascites or jaundice with 5 non-reversible cases vs 5 of 29 patients (17%) without cirrhosis (all reversible cases) (p=.001).In all cases of non-reversible toxic effects, patients had received whole-liver sirt.Treatment related adverse events (relationship to therasphere not specified in article):rash (allergic reaction); renal failure; neurological disorders (peripheral sensorimotor neuropath); nausea; abdominal pain; vomiting; diarrhea; dysphagia; neutropenia (decrease white blood cell); febrile neutropenia (fever); anaemia; thrombosis; lymphopenia; cholecystitis; cholangitis; decreased appetite and weight loss (anorexia;); pain; mucosal inflammation (gi injury, ulceration); edema; administration site reaction; general physical health deterioration (malaise); epistaxis; oral fungal infection; palmar-planatar erythrodysaesthesia syndrome (skin reaction).Events of asthenia; hepatic dysfunction and failure; ascites; disease progression and related deaths are already captured and reported as applicable in cases: btg00430; btg00431; btg00432; btg00433; btg00434; btg00435 and have been removed from this case (mdr reports 3002124545-2015-00085 and 3002124545-2015-00086 refer).

• Brand Name: THERASPHERE
• Type of Device: YTTRIUM-90 GLASS MICROSPHERES, PRODUCT CODE: NAW
• Manufacturer (Section D): BIOCOMPATIBLES UK LTD; chapman house farnham bus park; weydon lane; farnham, GU9 8 QL; UK GU9 8QL
• Manufacturer (Section G): BIOCOMPATIBLES UK; chapman house; weydon lane; farnham, GU9 8 QL; UK GU9 8QL
• Manufacturer Contact: sandra bausback-aballo ; 300 four falls corporate cente; 300 conshohocken state road; west conshohocken,, PA 19428-2998 ; 6103311537
• MDR Report Key: 9320350
• MDR Text Key: 166542459
• Report Number: 3002124543-2019-00063
• Device Sequence Number: 1
• Product Code: NAW
• Combination Product (y/n): N
• Reporter Country Code: FR
• PMA/PMN Number: H980006
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: foreign,health professional,l
• Reporter Occupation: Physician
• Type of Report: Initial
• Report Date: 11/11/2019

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 11/14/2019
• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: No
• Device Operator: Health Professional
• Device Model Number: UNKNOWN
• Device Catalogue Number: N/A
• Device Lot Number: UNKNOWN
• Was Device Available for Evaluation?: No
• Is the Reporter a Health Professional?: Yes
• Date Manufacturer Received: 11/11/2019
• Was Device Evaluated by Manufacturer?: Device Not Returned to Manufacturer
• Is the Device Single Use?: Yes
• Is This a Reprocessed and Reused Single-Use Device?: No
• Type of Device Usage: Initial
• Patient Sequence Number: 1
• Patient Outcome(s): Other