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 Death (1802); Encephalopathy (1833); Hepatitis (1897); Liver Damage/Dysfunction (1954); Therapeutic Response, Decreased (2271); Ascites (2596); Abdominal Distention (2601); Multiple Organ Failure (3261)

Event Type  Death  

Event Description

Hepatic failure [hepatic failure]; reild (radiation-induced liver disease) [radiation hepatitis]; decompensated cirrhosis [hepatic cirrhosis]; worsening encephalopathy [encephalopathy]; increasing abdominal girth and weight [abdominal distension]; partial response of the smaller tumours [therapeutic response decreased].Case description: information received on 29-mar-2017 this spontaneous medical device report was received from a literature article by braat et al.Entitled "hepatobiliary scintigraphy may improve radioembolization treatment planning in hcc patients" published in the ejnmmi research journal regarding a (b)(6) male patient.The patient was initially included in a multicenter randomised controlled trial in 2012 comparing tace and transarterial radioembolization (re) in patients with unresectable hepatocollular carcinoma (hcc) (the trace study; (b)(4)).The patient's medical history included liver cirrhosis due to alcohol abuse, screening with dynamic contrast-enhanced magnetic resonance imaging (mri), bone scintigraphy and angiography and a 99mtc-mebrofenin hepatobiliary scintigraphy, multifocal hypervascular mass in segments 5 and 8 of the liver (right lobe) with contrast washout, consistent with hcc, diagnosed at ultrasonography and liver ct.The largest tumour measured 3.7 cm (tumour involvement 1%).Splenomegaly and gastro-esophageal varices were also present, but no ascites or portal vein thrombosis was observed.On the day of treatment, the patient was graded as child-pugh grade a6/albi score grade 1.The patient's concomitant medications included tc-99m macroaggregated albumin intra-arterially injected for planar scintigraphy and single-photon emission computed tomography (spect)/ ct used to calculate the lung shunt fraction (lsf) and to detect other extrahepatic deposition, 99mtc-mebrofenin for the hepatobiliary scintigraphiesand coumarin derivates, for unknown indication.The lung shunt fraction (lsf) was calculated at 9% using spect/ ct.On an unspecified date, the patient was treated with therasphere (yttrium-90 glass microspheres), 3,1 gbq, target dose 80 gy, in the right liver lobe for hcc (lot number and expiration date were not reported).On the same day, a post-treatment 90y-positron emission tomography (pet)/ct was performed to assess the activity distribution and showed adequate targeting of the lesion in segments 5 (306 gy) and 8 (376 gy).The average absorbed dose of the non-tumorous liver parenchyma was 33 gy.On an unspecified date, twelve days after treatment, the patient visited the outpatient clinic with complaints of increasing abdominal girth and weight.He was treated with a low sodium diet and diuretics.The outcome of the event was unknown.On an unspecified date, six weeks thereafter, the patient was readmitted because of decompensated cirrhosis with worsening encephalopathy.The outcome was unknown.On an unspecified date, at 3-month follow-up, laboratory tests showed grade 2 bilirubin increased (2.4 mg/dl), grade 3 albumin decreased (20 g/l), grade 1 alp, ast and alt toxicity and an elevated ammonia serum value (60 micromol/l).Concurrent liver ct showed ascites in all quadrants, shrinkage of the liver and partial necrosis of the hcc's (partial response of the smaller tumours and stable disease of the largest tumour).Evaluation of the 99mtc-mebrofenin hepatobiliary scintigraphies (with showed a whole liver function decline from 3.0 to 2.4%/min/m2.The function of the treated right hemiliver declined from 2.3 to 1.6%/min/m2, without evident hypertrophy of the left hemiliver (0.8 vs 0.7%/min/m2).On an unspecified date, the patient died 4 months after re due to hepatic failure, probably caused by radioembolization-induced liver disease (reild).The authors did not assess the seriousness of the events however considered that the rapid clinical deterioration was due to reild.Additionally, the authors considered that the pre-treatment clinical, laboratory and imagining parameters were within acceptable limits for treatment, but did not predict the severe toxicity encountered, although the cases involved lobar treatments only.The company considered the event hepatic failure and radioembolization-induced liver disease as serious (fatal) and the events decompensated cirrhosis and worsening encephalopathy as serious (hospitalization) and the events increasing abdominal girth and weight and partial response of the smaller tumours as non-serious.This case is linked to cases (b)(4) from the same literature article.Follow-up information will be requested.Case comment: hepatic failure, radiation hepatitis, encephalopathy and hepatic cirrhosis are considered anticipated according to therasphere current reference safety information whereas abdominal distension and therapeutic response decreased are unanticipated.In line with the assessment made by the author, the company considered that hepatic failure, radiation hepatitis, encephalopathy, hepatic cirrhosis and abdominal distension are related to the use of therasphere based upon temporal relationship and knowledge of the product.However, the patient's medical history of liver cirrhosis due to alcohol abuse might have contributed to the events.In absence of an assessment made by the author, the company considered that therapeutic response decreased is not related to the use of therasphere and rather related to underlying disease.There was no report of deficiency or malfunction.This single case report does not modify the risk benefit balance of therasphere.The company is continuously monitoring all respective reports received and, based on cumulative experience, will reevaluate the available evidence on an ongoing basis.

Event Description

Hepatic failure [hepatic failure].Reild (radiation-induced liver disease) [radiation hepatitis].Decompensated cirrhosis [hepatic cirrhosis].Worsening encephalopathy [encephalopathy].Increasing abdominal girth and weight [abdominal distension].Partial response of the smaller tumours [therapeutic response decreased].Case description: information received on 29-mar-2017.This spontaneous medical device report was received from a literature article by braat et al.Entitled "hepatobiliary scintigraphy may improve radioembolization treatment planning in hcc patients" published in the ejnmmi research journal regarding a (b)(6) male patient.The patient was initially included in a multicenter randomised controlled trial in 2012 comparing tace and transarterial radioembolization (re) in patients with unresectable hepatocellular carcinoma (hcc) (the trace study; (b)(4)).The patient's medical history included liver cirrhosis due to alcohol abuse, screening with dynamic contrast-enhanced magnetic resonance imaging (mri), bone scintigraphy and angiography and a 99mtc-mebrofenin hepatobiliary scintigraphy, multifocal hypervascular mass in segments 5 and 8 of the liver (right lobe) with contrast washout, consistent with hcc, diagnosed at ultrasonography and liver ct.The largest tumour measured 3.7 cm (tumour involvement 1%).Splenomegaly and gastro-esophageal varices were also present, but no ascites or portal vein thrombosis was observed.On the day of treatment, the patient was graded as child-pugh grade a6/albi score grade 1.The patient's concomitant medications included tc-99m macroaggregated albumin intra-arterially injected for planar scintigraphy and single-photon emission computed tomography (spect)/ ct used to calculate the lung shunt fraction (lsf) and to detect other extrahepatic deposition, 99mtc-mebrofenin for the hepatobiliary scintigraphies and coumarin derivates, for unknown indication.The lung shunt fraction (lsf) was calculated at 9% using spect/ ct.On an unspecified date, the patient was treated with therasphere (yttrium-90 glass microspheres), 3,1 gbq, target dose 80 gy, in the right liver lobe for hcc (lot number and expiration date were not reported).On the same day, a post-treatment 90y-positron emission tomography (pet)/ct was performed to assess the activity distribution and showed adequate targeting of the lesion in segments 5 (306 gy) and 8 (376 gy).The average absorbed dose of the non-tumorous liver parenchyma was 33 gy.On an unspecified date, twelve days after treatment, the patient visited the outpatient clinic with complaints of increasing abdominal girth and weight.He was treated with a low sodium diet and diuretics.The outcome of the event was unknown.On an unspecified date, six weeks thereafter, the patient was readmitted because of decompensated cirrhosis with worsening encephalopathy.The outcome was unknown.On an unspecified date, at 3-month follow-up, laboratory tests showed grade 2 bilirubin increased (2.4 mg/dl), grade 3 albumin decreased (20 g/l), grade 1 alp, ast and alt toxicity and an elevated ammonia serum value (60 micromol/l).Concurrent liver ct showed ascites in all quadrants, shrinkage of the liver and partial necrosis of the hcc's (partial response of the smaller tumours and stable disease of the largest tumour).Evaluation of the 99mtc-mebrofenin hepatobiliary scintigraphies (with showed a whole liver function decline from 3.0 to 2.4%/min/m2.The function of the treated right hemiliver declined from 2.3 to 1.6%/min/m2, without evident hypertrophy of the left hemiliver (0.8 vs 0.7%/min/m2).On an unspecified date, the patient died 4 months after re due to hepatic failure, probably caused by radioembolization-induced liver disease (reild).The authors did not assess the seriousness of the events however considered that the rapid clinical deterioration was due to reild.Additionally, the authors considered that the pre-treatment clinical, laboratory and imagining parameters were within acceptable limits for treatment, but did not predict the severe toxicity encountered, although the cases involved lobar treatments only.The company considered the event hepatic failure and radioembolization-induced liver disease as serious (fatal) and the events decompensated cirrhosis and worsening encephalopathy as serious (hospitalization) and the events increasing abdominal girth and weight and partial response of the smaller tumours as non-serious.This case is linked to cases (b)(4) from the same literature article.Follow-up information will be requested.Final assessment on 02-may-2017: follow up information has been sought to further investigate the events but no new information has been received.After four follow up attempts, the case is considered lost to follow up.No device failure has been identified as a result of this adverse events.It has been assessed that no corrective action is necessary at this time and the report is considered final.Case comment: hepatic failure, radiation hepatitis, encephalopathy and hepatic cirrhosis are considered anticipated according to therasphere current reference safety information whereas abdominal distension and therapeutic response decreased are unanticipated.In line with the assessment made by the author, the company considered that hepatic failure, radiation hepatitis, encephalopathy, hepatic cirrhosis and abdominal distension are related to the use of therasphere based upon temporal relationship and knowledge of the product.However, the patient's medical history of liver cirrhosis due to alcohol abuse might have contributed to the events.In absence of an assessment made by the author, the company considered that therapeutic response decreased is not related to the use of therasphere and rather related to underlying disease.There was no report of deficiency or malfunction.This single case report does not modify the risk benefit balance of therasphere.The company is continuously monitoring all respective reports received and, based on cumulative experience, will reevaluate the available evidence on an ongoing basis.

Manufacturer Narrative

The case comment reported in the initial and follow up 1 report remains unchanged.There was no device malfunction reported.No additional information will be reported in association with this case.

Event Description

This is a follow up #2 submitted to report additional information received from the physician on 04 may 2018.Refer to initial report and follow up #1 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 19 mar 2018.Limited information was reported in response to the request.Additional information reported: hepatic tumor identification, including the kind of tumor, tumor burden in the liver, date and method of identification: hcc, multifocal right lobe, largest tumor 3.7 cm, cirrhosis, child-pugh a6.Calculation formula for required dose assessment: mird; 80 gy, 3.1 gbq.Pre-procedural hepatic angiogram finding, and follow up procedure: uncomplicated, maa rha.Lung shunt: 9.5% lung shunt fraction.Follow up data, at the day of administration, in 1, 4, 8, 12 weeks and the significant findings in the follow up: at 3 months bilirubin grade 2 tox (2.4 mg/dl), grade 3 albumin (20 g/l), ascites, encephalopathy.On ct pr of tumors.Death 4 months after treatment.Description of sae events, significant finding, lab data, mitigation process, and the patient outcome: reild (radioembolixation induced liver disease).Assessment of the relationship to the device: most likely related to therasphere.

• 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 falls corp cntr - 380; 300 conshohocken st. rd.; west conshohocken, PA 19428-2998 ; 6103311537
• MDR Report Key: 6510785
• MDR Text Key: 73348205
• Report Number: 3002124543-2017-00014
• Device Sequence Number: 1
• Product Code: NAW
• Combination Product (y/n): N
• Reporter Country Code: NL
• 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,Followup,Followup
• Report Date: 05/04/2018

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 04/21/2017
• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: No
• Device Operator: Physician
• Device Model Number: UNKNOWN
• Device Lot Number: UNKNOWN
• Was Device Available for Evaluation?: No
• Is the Reporter a Health Professional?: Yes
• Was the Report Sent to FDA?: No
• Date Manufacturer Received: 05/04/2018
• 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
• Treatment: MEBROFENIN (MEBROFENIN); TECHNETIUM (99M TC) DMSA
• Patient Outcome(s): Death; Hospitalization
• Patient Age: 74 YR