[139859976]
3 therasphere? Vials were used to treat this patient, it cannot be determined which device contributed to this clinically significant event. Refer to mdr 3002124543-2019-00022 and 3002124543-2019-00023 for the other device associated with this event. (b)(4). Subject: (b)(6). Last sae report: 14 mar 2019. Sae: liver failure (hepatic failure). This report concerns subject (b)(6), a male subject born in (b)(6), who was enrolled in study (b)(6)". On (b)(6) 2018, the subject was randomized to receive treatment with therasphere? For metastatic colorectal carcinoma and second-line chemotherapy. On (b)(6) 2018, the subject received first cycle of second-line chemotherapy, folfiri regimen (irinotecan 337 mg intravenous (iv), folinic acid 749 mg iv and fluorouracil 749 mg and 4495 mg iv which completed on (b)(6) 2019). On (b)(6) 2018, the subject received treatment with total 3 vials of therasphere?. The right hepatic lobe was treated with two vials (lot no 1899055, expiry date: 23 feb 2018 and 1899048, expiry date: 16 feb 2018) at a dose of 119. 89 gy and 110. 91 gy (segment 8 only). One vial was administered in the left hepatic lobe (lot no 1899048, expiry date: 16 feb 2018) at a dose of 115. 34 gy. On (b)(6) 2018, the subject received most recent cycle (fifteenth) of second-line chemotherapy, folfiri regimen (irinotecan 236 mg iv, folinic acid 524 mg iv and fluorouracil 524 mg iv and 3147 mg iv which completed on (b)(6) 2018), prior to the event. There are no relevant medical history or concomitant medications to the event. As on (b)(6) 2019, the subject had disease progression. On (b)(6) 2019, the subject visited emergency room with complaints of epigastric pain. Laboratory test showed creatinine 2. 21 mg/dl (normal range: 0. 6 to 1. 2). On (b)(6) 2019, the subject's laboratory test showed creatinine 2. 38 mg/dl (normal range: 0. 6 to 1. 2) (probably due to diuretics), bilirubin 8. 4 mg/dl (normal range: 0. 3 to 1. 1), aspartate transaminase (ast) 141 u/l (normal range: 6 to 40), alanine aminotransferase (alt) 104 u/l (normal range: 6 to 40) and gamma glutamyltransferase 827 u/l (normal range: 8 to 61). On (b)(6) 2019, the subject had albumin of 1. 9 mg/dl (normal range: 3. 5 to 5. 0). With these laboratory tests the subject was diagnosed with liver failure (hyperbilirubinemia and hypoalbuminemia) with massive ascites. The subject was treated with following medications: sodium chloride 500 ml iv and then 1000 ml iv every 12 hours. 500 ml iv every 8 hours from (b)(6) 2019, 500 ml iv every 12 hours from (b)(6) 2019. Sodium chloride and lactate 500 ml iv every 6 hours from (b)(6) 2019. Glucose 500 ml iv every 12 hours on (b)(6) 2019 and on (b)(6) 2019. Metamizole 2000 mg iv every 8 hours on (b)(6) 2019. Metoclopramide 10 mg iv every 8 hours from (b)(6) 2019. Morphine, 3 mg iv every 8 hours from (b)(6) 2019. Omeprazole 40 mg iv on (b)(6) 2019. Ondansetron 4 mg iv on (b)(6) 2019 and 4000 mg iv every 8 hours from (b)(6) 2019. Paracetamol 1 gm iv on (b)(6) 2019 and 1 gm iv every 8 hours from (b)(6) 2019. Propranolol 20 mg oral every 12 hours from (b)(6) 2019. Tramadol 50 mg iv on (b)(6) 2019. Ciprofloxacin 400 mg, every 24 hours, iv from (b)(6) 2019 and 500 mg, every 12 hours, oral from (b)(6) 2019. On (b)(6) 2019, the subject recovered with sequelae from the event of liver failure and was discharged from the hospital. On (b)(6) 2019, pain along with bilirubin and creatinine (1. 73, normal range: 0. 6 to 1. 2) was improved in subject. Anorexia and asthenia still persisted and physical exam showed semiology of ascites. Gastroscopy showed smaller varices compared to previous gastroscopy. Diuretics were resumed to try to avoid paracentesis. The investigator assessed the event of liver failure as grade-3 (severe) in intensity and serious due to hospitalization and other: clinically significant and definitely related to study device, unrelated to study procedure, probably related second line chemotherapy and other: first line chemotherapy. To the investigator, deterrent for decompensation was reported as urinary infection (pyuria), disease progression (elevation of tumoral markers), administration of chemotherapy and liver ablation (microwave). Per investigator, there is no other alternative explanation for portal hypertension after the study done by gastroenterologists. As portal hypertension was extremely infrequent before the era of selective internal radiation therapy (sirt) in the course of metastatic colorectal carcinoma. Besides there were evidence in literature as well. The lapse of time since the sirt and the event is common in the previously reported cases and disease progression could be the common deterrent. The reason to consider that first line has to be considered as probably related is that previous exposure to oxaliplatin is common rule in the formerly reported cases. Oxaliplatin is a well-known hepato-toxic drug and regenerative nodular hyperplasia is the pathologic finding. The company assessed the event as probably related to study device and possibly related to second line chemotherapy. The event was considered as not related to study procedure. No additional information is expected at this time.
Patient Sequence No: 1, Text Type: D, B5