MAUDE Adverse Event Report: BIOCOMPATIBLES UK LTD THERASPHERE; YTTRIUM-90 GLASS MICROSPHERES

Model Number UNKNOWN

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

Patient Problems Chest Pain (1776); Death (1802); Edema (1820); Encephalopathy (1833); Liver Damage/Dysfunction (1954); Heart Failure (2206); Ascites (2596)

Event Date 06/21/2017

Event Type  Death  

Manufacturer Narrative

The lot numbers for the therasphere doses were not reported.Disease progression, liver decompensation (edema, ascites, encephalopathy) and death are anticipated adverse events listed in the ifu.This patient died 6 years after diagnosis/2 years after the first therasphere treatment/5 months after the last treatment.Disease progression is considered not related to tace/therasphere, while liver decompensation, edema, ascites and encephalopathy are considered possibly related.This patient's death is considered unlikely related to therasphere.There is not enough information to determine the difference in disease progression and liver decompensation due to therasphere and/or tace.This event is being reported in an abundance of caution; therasphere as a contributing factor could not be ruled out.This patient was an outside referral to the reporting facility and did not receive the reported therasphere treatment at the reporting facility.No further information is available.The cause of death is undetermined.

Event Description

On (b)(6) 2017, clinical research coordinator from university of (b)(6) forwarded a completed medwatch form with the following information.It could not be determined if this user facility report was submitted to the fda.A (b)(6) male patient was diagnosed with hepatocellular carcinoma (hcc) in (b)(6) 2011 by liver biopsy.This patient had a history of coronary artery disease, hypertension, diabetes, and right carotid endarcterectomy.He received tace to segment 8 of the right lobe, twice, on (b)(6) 2012 and again on (b)(6) 2013.Imaging conducted in (b)(6) 2015 revealed new lesions.The patient received the first of three therasphere treatments on (b)(6) 2015 to segment 8 of the right lobe.The patient was then administered a deb-tace on (b)(6) 2016 to segment 2 of the left lobe.The second round of therasphere was administered on 05/2016 as a right lobar treatment.Then on (b)(6) 2016, the patient had another round of tace delivered to segment 4 of left lobe.Imaging was conducted on (b)(6) 2017 and revealed further hcc progression.The patient received his third, and final, therasphere treatment on (b)(6) 2017 delivered left lobar.The patient's health started to deteriorate several months after his final y-90 treatment on (b)(6) 2017.The patient went to his primary care provider on (b)(6) 2017 complaining of severe leg swelling and weeping from the shin.Fluid was clear and no purulence.The patient was seen by gastroenterology on (b)(6) 2017 for abdominal distention and discomfort.Providers impression was that he has had some decompensation of the liver with evidence of edema, ascites and new onset of mild encephalopathy.The patient was admitted to ed on (b)(6) 2017 for shortness of breath and chest pain.Ct conducted that day showed recurrent/residual hcc.Lab work indicated anemia (hb= 6.9) and bnp (629) indicating worsening heart failure.The patient passed away on (b)(6) 2017.This patient was an outside referral to the reporting facility and did not receive the reported therasphere treatment at the reporting facility.No further information available.The cause of death is undetermined.It was reported that all of the patient's liver labs were normal, but he started to express symptomology of liver decompensation.Therasphere doses reported: #1: (b)(6) 2015 - 78.2 mci.#2: (b)(6) 2016 - 75.73 mci.#3: (b)(6) 2017 - 33.9 mci.Tace procedures: #1: (b)(6) 2012 - segment 8, right lobe.#2: (b)(6) 2013 - segment 8, right lobe.#3: (b)(6) 2016 - segment 2, left lobe (deb-tace).#4: (b)(6) 2016 - segment 4, left lobe.

Manufacturer Narrative

Following the submission of an annual report to the fda on 23 feb 2018, the fda requested additional detailed patient and procedure information to aid in reviewing the saes reported in the annual update.Additional information was reported in response to the request.An assessment of the relationship to the device was not provided by th physician.The company assessment previously reported remains unchanged.Refer to initial mdr.

Event Description

This is a follow up #1 submitted to report additional information received from the physician on 02 apr 2018.Refer to initial report for event description.Following the submission of an annual report to the fda on 23 feb 2018, the fda requested additional detailed patient and procedure information to aid in reviewing the saes reported in the annual update.The request for additional information was sent to the physician via email on 21 mar 2018.Limited information was reported in response to the request.Additional information reported: - patient age, gender, past medical history, e.G., (b)(6), or alcoholic hepatitis, the presence of cirrhosis, mild, moderate, or advanced, and preliminary screening lfts, other lab data.Patient age, sex & medical history previously reported.Refer to initial mdr additional medical history received: the emergency department notes on (b)(6) 2017 list an extensive patient active problem list: degeneration of lumbar or lumbosacral intervertebral disc, esophageal reflux, dyspnea and respiratory abnormality, hyperlipidemia with target ldl less than 100, chronic kidney disease (stage 3), liver lesion, hypothyroidism, coronary artery disease, overweight, chronic pain syndrome, anemia, positive fecal immunochemical test, iron deficiency anemia, gi bleed, acute chest pain, bilateral lower extremity edema and pedal edema.In addition, a history of uncontrolled type 2 diabetes mellitus with complication, copd, malignant neoplasm of primary liver, (b)(6), pancytopenia, alcoholic cirrhosis of the liver with ascites, thrombocytopenia.The emergency department physical exam notes on (b)(6) 2017 notes the patient's skin to be appearing mildly jaundice.- hepatic tumor identification, including the kind of tumor, tumor burden in the liver, date and method of identification (biopsy, imaging, ct, mri, or other method).Previously reported.Refer to initial mdr pathology results reported: the liver needle biopsy on (b)(6) 2011 diagnosed well differentiated hepatocellular carcinoma, background of (b)(6) with piecemeal necrosis and portal fibrosis, focally bridging (grade 2, stage 3), and known (b)(6).- pre-procedural hepatic angiogram finding, and follow up procedure.The pre-procedure mr of abdomen with and without contract on (b)(6) 2017 revealed the following: cirrhosis and evidence of portal hypertension with evolving post treatment changes in the right lobe.Well residual right lobe (b)(6) is difficult to exclude, no highly suspicious areas are identified.A 3.4 cm optn 5t lesion with significant enhancement in the posterior left lobe has enlarged abd is consistent with (b)(6) recurrence.Satellite li_rads 4 nodule is probably (b)(6) but has not significantly changed in size.Enlarging li-rads 4 mass along the border of segments 2 and 3.Based on this exam only, the patient is within the milan criteria.Additional significant findings: bilobed spleen is moderately enlarged (similar to last exam), renal cyst (right superior pole/right extrarenal pelvis) and trace ascites.The pre-procedural angiogram on (b)(6) 2017 demonstrated multiple tumor blushes arising from the hepatic segment 2 and 3 arteries.The right gastric artery was arising from the proximal aspect of the left hepatic artery.The microcatheter tip was positioned into the distal aspect of the left hepatic artery and maa was administered very slowly.The plan is to administer radioembolization very slowly to the left hepatic lobe with the microcatheter and distal left hepatic artery.No procedural complications were noted.Post procedure mr of abdomen with and without contrast on (b)(6) 2017 revealed the following: limited study due to suboptimal bolus timing on the arterial phase.Cirrhosis and evidence of portal hypertension including mild splenomegaly and small volume ascites.Post radioembolization changes are again noted in hepatic segment 2 with a crescentic region of hypointensity along the posterior margin and capsule appearance.Unfortunately, washout cannot be assessed on the current examination given the lack of arterial phase timing, however this region demonstrated arterial enhancement on the prior exam and there is concern for residual/recurrent disease.No significant change in 1.5 cm lesion in the lateral aspect of hepatic segment 2.Optn/lirads class 5a.Extensive post treatment changes in the right lobe of liver with areas of heterogeneous enhancement related to perfusion abnormalities, unchanged.Increase in size of right pleural effusion.Post procedure mr of abdomen with and without contrast on (b)(6) 2017 revealed the following: cirrhotic appearance of liver with small ascites.There are post treatment changes involving hepatic segment 5, 6 and 8 lesions.This exam will serve as a new baseline for future follow up.Optn 5b lesion in hepatic segment 4a with a satellite optn 5a lesion.Additionally, there is a lirads 4 lesion more superior within hepatic segment 4a.New subtle nodularity along the margin of previously treated hepatic segment 2 lesion.Attention to follow up, as this could represent early recurrence.- finding in lung shunt assessment.Therasphere doses: (b)(6) 2017 - lung shunt 1.97%.- assessment of the relationship to the device was not provided.Company assessment previously reported remains unchanged.Refer to initial mdr.

• Brand Name: THERASPHERE
• Type of Device: YTTRIUM-90 GLASS MICROSPHERES
• Manufacturer (Section D): BIOCOMPATIBLES UK LTD; farnham business park; weydon lane; farnham, surrey GU9 8 QL; UK GU9 8QL
• Manufacturer (Section G): BIOCOMPATIBLES UK LTD; farnham business park; weydon lane; farnham, surrey GU9 8 QL,; UK GU9 8QL,
• Manufacturer Contact: sandra bausback ; 300 four falss corp cnt - 380; 300 conshohocken st. rd.; west conshohocken, PA 19428-2998 ; 6103311537
• MDR Report Key: 7053012
• MDR Text Key: 92806970
• Report Number: 3002124543-2017-00052
• Device Sequence Number: 1
• Product Code: NAW
• Combination Product (y/n): N
• Reporter Country Code: US
• PMA/PMN Number: H980006
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: health professional,user faci
• Reporter Occupation: Physician
• Type of Report: Initial,Followup
• Report Date: 10/27/2017

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: No
• Device Operator: Physician
• 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
• Was the Report Sent to FDA?: No
• Initial Date Manufacturer Received: 10/27/2017
• Initial Date FDA Received: 11/22/2017
• Supplement Dates Manufacturer Received: 04/02/2018
• Supplement Dates FDA Received: 05/01/2018
• 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): Death
• Patient Age: 70 YR