MAUDE Adverse Event Report: BIOCOMPATIBLES UK LTD. THERASPHERE®

Lot Number	U584
Medical Device Problem Code	Adverse Event Without Identified Device or Use Problem (2993)
Health Effect - Clinical Code	Liver Damage/Dysfunction (1954)
Date of Event	05/02/2017
Type of Reportable Event	Serious Injury
Event or Problem Description
(b)(4).Subject# (b)(6).Last sae report: (b)(6) 2017.Sae: hepatic disorder; other radiation induced liver disease (chronic hepatic failure).This report concerns subject (b)(6), a (b)(6) female, who was enrolled in the 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) 2017, the subject received the first treatment with study device therasphere® with dosage of 126 gy to the right lobe and 129 gy to the left lobe.On (b)(6) 2017, the subject started first cycle of study treatment with second-line chemotherapy for metastatic colorectal carcinoma with folfiri regimen.On (b)(6) 2017, the subject started the fourth cycle of chemotherapy with folfiri regimen (irinotecan 250 mg iv, folinic acid 350 mg iv and fluorouracil 3500 mg iv in 46 hours).On (b)(6) 2017, the treatment with folfiri regimen was discontinued.The subject's relevant medical history included insulin diabetes ((b)(6) 2017-ongoing).The subject's concomitant medication included metformin 1 gm (po, bd from 2004 - ongoing), lantus insulin 18 iu (sc, od from (b)(6) 2015) and movicol (po, prn from (b)(6) 2017 - ongoing).On (b)(6) 2017, chemotherapy had been interrupted due to low platelet count.Radiation hepatitis was suspected and subject started on dexamethasone 4 mg daily.On (b)(6) 2017, the subject was hospitalized with abdominal pain, constipation and bloating.On admission liver function tests were abnormal.The subject was placed on iv fluids and ascetic tapping was performed.On (b)(6) 2017, deterioration in hepatic function with increase in ascetic fluid, pleural effusion and soft tissue edema was noted.On (b)(6) 2017 blood test showed abnormal liver function tests (alt 147 u/t (normal<40), bilirubin 22 umol/l (normal value 2-21), albumin 22 g/l (normal value 35-50) and alkaline phosphatase 341 iu/l (normal value 30-130).The subject was hence treated for radiation induced liver disease with defibrotide 6.2 mg/kg four times a day (for a maximum of 21 days).The subject was also taking 8 mg of dexamethasone iv daily.On (b)(6) 2017, the condition of the subject remained stable but serious.Liver function tests were also stable (alt 102 u/t (normal<40), bilirubin 26 umol/l (normal value 2-21), albumin 22 g/l (normal value 35-50) and alkaline phosphatase 370 iu/l (normal value 30-130) and no signs of hepatic encephalopathy were noticed.The subject was treated with defibrotide 6.25 mg/kg 6 hourly iv, dexamethasone 8 mg daily for radiation induced liver disease.Monitoring of ascites was also being performed with repeat drainage if required.Monitoring of diabetes and infection monitoring was also performed while the subject was hospitalized.The subject has not recovered from the event at the time of reporting this event.On (b)(6) 2017, the condition of the subject was serious but stable while reporting the follow up information.The subject discontinued participation in the study due to the event.The investigator assessed the event of hepatic disorder; other radiation induced liver disease as grade 4 (life-threatening) in intensity and serious due to hospitalization and as the event was life threatening.The event was considered as probably related to study device and procedure.The event was considered as possibly related to study treatment with second-line chemotherapy (folfiri regimen).The company agreed with investigator's assessment.A supplemental report will be submitted if additional relevant information is received.
Event or Problem Description
This is a follow up report to update test results, action taken subject and company assessment.Mfr report number: 3002124543-2017-00024.(b)(4).Subject (b)(6).Last sae report: (b)(6) 2017.Sae: hepatic disorder; other radiation induced liver disease (chronic hepatic failure).On (b)(6) 2017, the subject's ct scan showed slight recovery in liver.On (b)(6) 2017, the event of hepatic disorder other radiation induced liver disease resolved with sequelae and the subject was discharged home.The subject's condition was stable with reduction in ascites.Lts remained elevated but were stable and the subject was continued to be monitored at home.The treatment of subject with second line chemotherapy was discontinued due to the event, however participation in the study continued.The company assessed the event of hepatic disorder other radiation induced liver disease as grade 4 (life-threatening) in intensity and serious due to hospitalization and as it was a life-threatening experience.The event was considered as probably related to study device and possibly related to study second line chemotherapy treatment and to study procedure.No additional information is expected at this time.If additional information is received, a follow up report will be submitted.
Event or Problem Description
This follow-up report is being sent to correct pma/510(k) number to h980006.

• Brand Name: THERASPHERE®
• Common Device Name: THERASPHERE®
• Manufacturer (Section D): BIOCOMPATIBLES UK LTD.; chapman house farnham business; weydon lane; farnham,, surrey GU9 8 QL; UK GU9 8QL
• MDR Report Key: 6607535
• Report Number: 3002124543-2017-00024
• Device Sequence Number: 767850
• Product Code: NAW
• UDI-Device Identifier: 05060116920383
• UDI-Public: 05060116920383
• Combination Product (Y/N): N
• Initial Reporter Country: UK
• PMA/510(K) Number: H980006
• Number of Events Summarized: 1
• Summary Report (Y/N): N
• Device Implanted Year: 2017
• Reporter Type: Manufacturer
• Report Source: foreign,study
• Initial Reporter Occupation: Physician
• Remedial Action: Patient Monitoring
• Type of Report: Initial,Followup,Followup
• Report Date (Section B): 07/31/2017

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
• Operator of Device: Physician
• Device Expiration Date: 02/19/2017
• Device Lot Number: U584
• Was Device Available for Evaluation?: No
• Was the Report Sent to FDA?: No
• Event Location: Hospital
• Type of Report(Section G): Thirty-Day
• Initial Date Received by Manufacturer: 05/04/2017
• Supplement Date Received by Manufacturer: 07/07/2017; 07/07/2017
• Initial Report FDA Received Date: 06/02/2017
• Supplement Report FDA Received Date: 07/31/2017; 11/02/2017
• Is This a Single-Use Device that was Reprocessed and Reused on a Patient? (Y/N): No
• Patient Sequence Number: 1
• Concomitant Medical Products and Therapy/Usage Dates: FLUOROURACIL; FOLINIC ACID; IRINOTECAN; LANTUS INSULIN; METFORMIN; MOVICOL
• Outcome Attributed to Adverse Event: Hospitalization; Life Threatening
• Patient Age: 58 YR
• Patient Weight: 47