THERASPHERE
Report
- Report Number
- 3002124543-2019-00046
- Event Type
- Death
- Date Received
- May 29, 2019
- Date of Event
- October 5, 2015
- Report Date
- June 28, 2019
- Manufacturer
- BIOCOMPATIBLES UK LTD
- Product Code
- NAW
- UDI-DI
- 05060116920284
- PMA / PMN Number
- H980006
- Adverse Event
- Yes
- Report Source
- Manufacturer report
- Reporter Location
- CA, US
- Reporter Occupation
- PHYSICIAN
Narratives
THE EVENTS WERE REPORTED THROUGH A RETROSPECTIVE CLINICAL TRIAL. THE EVENTS ARE CONSIDERED SERIOUS DUE TO HOSPITALIZATION AND SUBSEQUENT DEATH OF PATIENT. ADDITIONAL INFORMATION WAS RECEIVED ON 28-JUN-2019: CORRESPONDENCE FROM THE PHYSICIAN WAS RECEIVED (B)(6) 2019 AS FOLLOWS: I REVIEWED THE ORIGINAL ACTIVITY CALCULATION SHEETS, AND THE SEGMENT 2/4 ARTERY AND THE SEGMENT 3 ARTERY WERE PRESCRIBED 117 GY EACH. PART OF SEG 4 WAS FED BY COLLATERAL FLOW FROM THE RIGHT LOBE, SO IT IS POSSIBLE THAT THE 2/4 VOLUME OF DISTRIBUTION WAS SMALLER THAN ANTICIPATED AND THE ABSORBED DOSE WAS HIGHER. I WILL NEED TO CHECK THE SEGMENTATION BY THE DR TO SEE WHETHER IT DIFFERS FROM THE ORIGINAL SEGMENTATION USED FOR ACTIVITY CALCULATION. FOLLOWING RECEIPT OF FURTHER INFORMATION RECEIVED (B)(6) 2019 - FURTHER INVESTIGATIONS OF INFORMATION CONFIRMED: WHAT WE KNOW IS 1. THE LIVER VOLUME DETERMINED BY MRI (ANATOMICAL) IS 1585 ML 2. PATIENT WAS TREATED WITH THERMOSPHERE: (B)(6) 2015, INFUSED IN THE RIGHT ARTERY AND THE ACTIVITY ADMINISTERED IN THE RIGHT LOBE IS [3.01- 0.09]X(1-7.4% LUNG SHUNT)= 2.7 GBQ 3. PATIENT WAS TREATED WITH THERMOSPHERE (B)(6) 2015, INFUSED IN THE RIGHT ARTERY THE DOSE TO THE LEFT LOBE AND THE VOLUME OF THE LEFT LOBE WERE 176 GY AND 478 ML THEN WE CAN CALCULATE: 1. ACTIVITY ADMINISTERED IN THE LEFT LOBE = 176X0.478X1.03/50X(1-7.4% LS)=1.88 GBQ 2. TOTAL ACTIVITY ADMINISTERED TO THE PATIENT IS 2.7+1.88=4.58 GBQ 3. DOSE TO THE WHOLE LIVER IS 4.58X50/1.578X1.03=120.26 GY THAT IS IN THE IFU THERE IS NO OFF-LABEL USE OF THE PRODUCT THE PATIENT HAS SLIGHT IMPAIRMENT OF LIVER FUNCTION AT BASELINE BILI1.5 ULN, ALBUMIN JUST AT THE LOWER NORMAL LIMIT, PORTAL HYPERTENSION WITH SLIGHT ASCITES, CHILD A6 AND HE WAS 83 YO BEFORE THE SECOND ADMINISTRATION THE BILIRUBIN HAD SLIGHTLY INCREASED. FINAL MEDICAL ASSESSMENT PERFORMED: (B)(6) 2019 PATIENT RECEIVED THE SECOND TREATMENT, THE LIVER FUNCTION HAS DEGRADATE COMPARED TO STUDY ENTRY ALBUMIN 26G/L, BILIRUBIN 2,3 MG LYMPHOPENIA IS A COMMON CONSEQUENCE OF TS TREATMENT, PATIENT EXPERIENCED SEPSIS AND PERITONEAL INFECTION, NOTED ON THE (B)(6) 2015. IN PATIENT WITH CIRRHOSIS AND PORTAL HYPERTENSION, SPONTANEOUS ASCITES/PERITONEAL INFECTION MAY OCCUR, BY BACTERIAL TRANSLOCATION OF DIGESTIVE BACTERIA THROUGH THE GUT WALL. THAT IS FAVOURED BY A LOW ALBUMIN LEVEL IN THE ASCITES (RESULT NOT KNOWN). PATIENT EXPERIENCED A REILD, THAT ASSOCIATE THE CLINICAL SYMPTOMS OF BOTH ASCITES OR INCREASING ABDOMINAL GIRTH AND JAUNDICE OR HYPERBILIRUBINEMIA. REILD IS THE CONSEQUENCE OF OBSTRUCTION OF THE SINUSOID AS AN EFFECT OF RADIATION THAT CAUSE PORTAL HYPERTENSION AND CHOLESTASIS WITH THE INFORMATION AVAILABLE OF ACTIVITY ADMINISTERED AND LIVER VOLUME THE DOSE TO THE WHOLE LIVER IS CALCULATED AS FOLLOWS WITH THE MIRD FORMULA= 4.58X50/1.578X1.03= 120.26 GY THAT IS IN THE IFU FOR THE CURRENT SITUATION, THE PATIENT MIGHT HAVE EXPERIENCE A REILD THAT CAUSE LIVER DYSFUNCTION AND THEREFORE RENAL DYSFUNCTION DUE TO A HIGHER DOSE TO NON-TUMORAL LIVER TISSUE THAT WAS ABOVE HIS OWN TOLERANCE. SEPSIS: SEVERITY 4; SERIOUS; CAUSALITY - HEPATIC FAILURE; ANTICIPATED PERITONEAL INFECTION: SEVERITY 3; SERIOUS; CAUSALITY - HEPATIC FAILURE; ANTICIPATED HEPATIC FAILURE; SEVERITY 4; SERIOUS - FATAL; RELATED TO DEVICE; ANTICIPATED ACUTE KIDNEY INJURY: SEVERITY 3; SERIOUS; CAUSALITY - HEPATIC FAILURE; ANTICIPATED LYMPHOCYTE COUNT DECREASED: SEVERITY 3; NON-SERIOUS; RELATED TO DEVICE; ANTICIPATED BLOOD BILIRUBIN INCREASED: SEVERITY 3; SERIOUS; CAUSALITY - HEPATIC FAILURE; ANTICIPATED THIS REPORT IS CONSIDERED FINAL.
THE EVENTS WERE REPORTED THROUGH A RETROSPECTIVE CLINICAL TRIAL. THE EVENTS ARE CONSIDERED SERIOUS DUE TO HOSPITALIZATION AND RELATED TO THERASPHERE ADMINISTRATION. BTG MEDICAL ASSESSMENT: SUBJECT (B)(4) IS AN 83 YEAR-OLD MALE PATIENT. DIAGNOSED WITH HCC ON (B)(6) 2015. PRESENCE OF PORTAL HYPERTENSION. BILOBAR TUMOR, BCLC B, INDEX TUMOR OF 44 MM OF THE RIGHT LIVER. ETIOLOGIC ASSOCIATIONS: LIVER CIRRHOSIS. ALCOHOLIC CIRRHOSIS. NO PRIOR SORAFENIB TREATMENT BEFORE THERASPHERE AND NO DISEASE SPECIFIC SURGERY. PATIENT WAS TREATED WITH THERASPHERE: (B)(6) 2015, INFUSED IN THE RIGHT ARTERY ACTIVITY AT START OF INFUSION 3.01 GBQ; RESIDUALS REMAINING 0.09GBQ. LUNG SHUNT FRACTION (B)(4)%. TREATMENT TO RIGHT LOBE. 2ND TREATMENT TO LEFT LOBE ON (B)(6) 2015. 2ND ABSORBED DOSE TO THE PERFUSED VOLUME 176.4GY. PATIENT RECEIVED THE SECOND TREATMENT, THE LIVER FUNCTION HAS DEGRADATED COMPARED TO STUDY ENTRY: ALBUMIN 26G/L, BILIRUBIN 2,3 MG . LYMPHOPENIA IS A COMMON CONSEQUENCE OF TS TREATMENT, PATIENT EXPERIENCED A REILD, THAT ASSOCIATES THE CLINICAL SYMPTOMS OF BOTH ASCITES OR INCREASING ABDOMINAL GIRTH AND JAUNDICE OR HYPERBILIRUBINEMIA. REILD IS THE CONSEQUENCE OF OBSTRUCTION OF THE SINUSOID AS AN EFFECT OF RADIATION THAT CAUSE PORTAL HYPERTENSION AND CHOLESTASIS. DOSE TO THE NORMAL LIVER WAS ABOVE THE IFU RECOMMENDATION WHICH IS 80-150 GY TO THE WHOLE LIVER AND THE PATIENT RECEIVED : 223 RIGHT LIVER AND 176 GY LEFT LIVER CONSEQUENTLY, FOR THE CURRENT SITUATION, THE PATIENT MIGHT HAVE EXPERIENCED A REILD THAT CAUSED LIVER DYSFUNCTION AND THEREFORE RENAL DYSFUNCTION. ALL EVENTS ARE ANTICIPATED ADVERSE EVENTS LISTED IN THE RISK MANAGEMENT DOCUMENTATION/IFU. NO DEVICE MALFUNCTION WAS REPORTED AND NO CORRECTIVE AND PREVENTIVE ACTION (CAPA) PLAN HAS BEEN IDENTIFIED. THE LOT NUMBER ASSOCIATED WITH THE THERASPHERE ADMINISTRATION WAS NOT REPORTED, THEREFORE NO INVESTIGATION COULD BE PERFORMED. ADDITIONAL INFORMATION HAS ALSO BEEN SOUGHT REGARDING HOSPITAL ADMISSION AND DISCHARGE DATES IF ADDITIONAL INFORMATION BECOMES AVAILABLE, A FOLLOW UP REPORT WILL BE SUBMITTED. NO OTHER INFORMATION IS AVAILABLE THAT COULD CONFIRM/DENY THE ALLEGED EVENT. AT THIS TIME THIS REPORT IS CONSIDERED FINAL. BTG MEDICAL ASSESSMENT OF ADDITIONAL ADVERSE EVENT REPORTED (B)(6) 2019: PATIENT EXPERIENCED SEPSIS AND PERITONEAL INFECTION, NOTED ON THE (B)(6) 2015. IN PATIENTS WITH CIRRHOSIS AND PORTAL HYPERTENSION, SPONTANEOUS ASCITES/PERITONEAL INFECTION MAY OCCUR, BY BACTERIAL TRANSLOCATION OF DIGESTIVE BACTERIA THROUGH THE GUT WALL. THAT IS FAVOURED BY A LOW ALBUMIN LEVEL IN THE ASCITES (RESULT NOT KNOWN). PATIENT EXPERIENCED A REILD, THAT ASSOCIATE THE CLINICAL SYMPTOMS OF BOTH ASCITES OR INCREASING ABDOMINAL GIRTH AND JAUNDICE OR HYPERBILIRUBINEMIA. REILD IS THE CONSEQUENCE OF OBSTRUCTION OF THE SINUSOID AS AN EFFECT OF RADIATION THAT CAUSE PORTAL HYPERTENSION AND CHOLESTASIS DOSE TO THE NORMAL LIVER WAS ABOVE THE IFU RECOMMENDATION WHICH IS 80-150 GY TO THE WHOLE LIVER AND THE PATIENT RECEIVED: 223 RIGHT LIVER AND 176 GY LEFT LIVER FOR THE CURRENT SITUATION, THE PATIENT MIGHT HAVE EXPERIENCE A REILD THAT CAUSE LIVER DYSFUNCTION AND THEREFORE RENAL DYSFUNCTION.
ADDITIONAL INFORMATION RECEIVED: 23-JUN-2019. ADMINISTERED ACTIVITY: 3.01GBQ, TOTAL PERFUSED VOLUME: 1107.3MM3 TREATMENT WAS ADMINISTERED THROUGH THE RIGHT HEPATIC ARTERY TO THE RIGHT LOBE OF THE LIVER. ADDITIONAL INFORMATION RECEIVED: 28-JUN-2019. PHYSICIAN REPORTED: I REVIEWED THE ORIGINAL ACTIVITY CALCULATION SHEETS, AND THE SEGMENT 2/4 ARTERY AND THE SEGMENT 3 ARTERY WERE PRESCRIBED 117 GY EACH. PART OF SEG 4 WAS FED BY COLLATERAL FLOW FROM THE RIGHT LOBE, SO IT IS POSSIBLE THAT THE 2/4 VOLUME OF DISTRIBUTION WAS SMALLER THAN ANTICIPATED AND THE ABSORBED DOSE WAS HIGHER. I WILL NEED TO CHECK THE SEGMENTATION BY THE DR TO SEE WHETHER IT DIFFERS FROM THE ORIGINAL SEGMENTATION USED FOR ACTIVITY CALCULATION.
AUTO-NOTIFICATION RECEIVED FROM DATATRAK (B)(6) 2019. SUBJECT (B)(4) IS AN 83 YEAR-OLD MALE PATIENT. DIAGNOSED WITH HCC ON (B)(6) 2015. PRESENCE OF PORTAL HYPERTENSION. BILOBAR TUMOR, BCLC B, INDEX TUMOR OF 44 MM OF THE RIGHT LIVER. ETIOLOGIC ASSOCIATIONS: LIVER CIRRHOSIS. ALCOHOLIC CIRRHOSIS. NO PRIOR SORAFENIB TREATMENT BEFORE THERASPHERE AND NO DISEASE SPECIFIC SURGERY. PATIENT WAS TREATED WITH THERASPHERE: (B)(6) 2015, INFUSED IN THE RIGHT ARTERY. ACTIVITY AT START OF INFUSION 3.01 GBQ; RESIDUALS REMAINING 0.09GBQ. LUNG SHUNT FRACTION (B)(6)%. TREATMENT TO RIGHT LOBE. 2ND TREATMENT TO LEFT LOBE ON (B)(6) 2015. 2ND ABSORBED DOSE TO THE PERFUSED VOLUME 176.4GY. CONCOMITANT MEDICATION: OCTREOTIDE (3 X PER DAY) (B)(6) 2015. ZOSYN (ONCE) (B)(6) 2015. ALDACTONE (25 MG PER DAY) (B)(6) 2015. LASIX (40 MG PER DAY) (B)(6) 2015. ON (B)(6) 2015: PATIENT EXPERIENCED: SEPSIS, HEPATIC FAILURE; ACUTE KIDNEY INJURY; LYMPHOCYTE COUNT DECREASED AND BLOOD BILIRUBIN INCREASE. PATIENT SUBSEQUENTLY DIED (CAUSE NOT REPORTED) (B)(6) 2015. ADDITIONAL INFORMATION RECEIVED: (B)(6) 2019. ON (B)(6) 2015 ADVERSE EVENT: PERITONEAL INFECTION. OUTCOME: NOT RECOVERED/NOT RESOLVED. THE EVENTS WERE NOT REPORTED TO BTG BY THE INVESTIGATOR IN 2015.
THE EVENTS WERE REPORTED THROUGH A RETROSPECTIVE CLINICAL TRIAL. THE EVENTS ARE CONSIDERED SERIOUS DUE TO HOSPITALIZATION AND RELATED TO THERASPHERE ADMINISTRATION. BTG MEDICAL ASSESSMENT: SUBJECT (B)(6) IS (B)(6) YEAR-OLD MALE PATIENT. DIAGNOSED WITH HCC ON (B)(6) 2015. PRESENCE OF PORTAL HYPERTENSION, BILOBAR TUMOR, BCLC B, INDEX TUMOR OF 44 MM OF THE RIGHT LIVER. ETIOLOGIC ASSOCIATIONS: LIVER CIRRHOSIS, ALCOHOLIC CIRRHOSIS, NO PRIOR SORAFENIB TREATMENT BEFORE THERASPHERE AND NO DISEASE SPECIFIC SURGERY. PATIENT WAS TREATED WITH THERASPHERE: (B)(6) 2015, INFUSED IN THE RIGHT ARTERY. ACTIVITY AT START OF INFUSION 3.01 GBQ; RESIDUALS REMAINING 0.09GBQ; LUNG SHUNT FRACTION 7.4%; TREATMENT TO RIGHT LOBE; 2ND TREATMENT TO LEFT LOBE ON (B)(6) 2015; 2ND ABSORBED DOSE TO THE PERFUSED VOLUME 176.4GY. PATIENT RECEIVED THE SECOND TREATMENT, THE LIVER FUNCTION HAS DEGRADATED COMPARED TO STUDY ENTRY: ALBUMIN 26G/L, BILIRUBIN 2,3 MG. LYMPHOPENIA IS A COMMON CONSEQUENCE OF TS TREATMENT. PATIENT EXPERIENCED A REILD, THAT ASSOCIATES THE CLINICAL SYMPTOMS OF BOTH ASCITES OR INCREASING ABDOMINAL GIRTH AND JAUNDICE OR HYPERBILIRUBINEMIA. REILD IS THE CONSEQUENCE OF OBSTRUCTION OF THE SINUSOID AS AN EFFECT OF RADIATION THAT CAUSE PORTAL HYPERTENSION AND CHOLESTASIS. DOSE TO THE NORMAL LIVER WAS ABOVE THE IFU RECOMMENDATION WHICH IS 80-150 GY TO THE WHOLE LIVER AND THE PATIENT RECEIVED : 223 RIGHT LIVER AND 176 GY LEFT LIVER CONSEQUENTLY, FOR THE CURRENT SITUATION, THE PATIENT MIGHT HAVE EXPERIENCED A REILD THAT CAUSED LIVER DYSFUNCTION AND THEREFORE RENAL DYSFUNCTION. ALL EVENTS ARE ANTICIPATED ADVERSE EVENTS LISTED IN THE RISK MANAGEMENT DOCUMENTATION/IFU. NO DEVICE MALFUNCTION WAS REPORTED AND NO CORRECTIVE AND PREVENTIVE ACTION (CAPA) PLAN HAS BEEN IDENTIFIED. THE LOT NUMBER ASSOCIATED WITH THE THERASPHERE ADMINISTRATION WAS NOT REPORTED, THEREFORE NO INVESTIGATION COULD BE PERFORMED. ADDITIONAL INFORMATION HAS ALSO BEEN SOUGHT REGARDING HOSPITAL ADMISSION AND DISCHARGE DATES IF ADDITIONAL INFORMATION BECOMES AVAILABLE, A FOLLOW UP REPORT WILL BE SUBMITTED. NO OTHER INFORMATION IS AVAILABLE THAT COULD CONFIRM/DENY THE ALLEGED EVENT. AT THIS TIME THIS REPORT IS CONSIDERED FINAL.
AUTO-NOTIFICATION RECEIVED FROM (B)(6) 23-MAY-2019. SUBJECT (B)(6) IS (B)(6) YEAR-OLD MALE PATIENT. DIAGNOSED WITH HCC ON (B)(6) 2015. PRESENCE OF PORTAL HYPERTENSION. BILOBAR TUMOR, BCLC B, INDEX TUMOR OF 44 MM OF THE RIGHT LIVER ETIOLOGIC ASSOCIATIONS: LIVER CIRRHOSIS, ALCOHOLIC CIRRHOSIS, NO PRIOR SORAFENIB TREATMENT BEFORE THERASPHERE AND NO DISEASE SPECIFIC SURGERY. PATIENT WAS TREATED WITH THERASPHERE: (B)(6) 2015, INFUSED IN THE RIGHT ARTERY - ACTIVITY AT START OF INFUSION 3.01 GBQ; RESIDUALS REMAINING 0.09GBQ; LUNG SHUNT FRACTION 7.4%; TREATMENT TO RIGHT LOBE; 2ND TREATMENT TO LEFT LOBE ON (B)(6) 2015; 2ND ABSORBED DOSE TO THE PERFUSED VOLUME 176.4GY. CONCOMITANT MEDICATION: OCTREOTIDE (3 X PER DAY) (B)(6) 2015, ZOSYN (ONCE) (B)(6) 2015, ALDACTONE (25 MG PER DAY) (B)(6) 2015, LASIX (40 MG PER DAY) (B)(6) 2015. (B)(6) 2015: PATIENT EXPERIENCED: SEPSIS, HEPATIC FAILURE; ACUTE KIDNEY INJURY; LYMPHOCYTE COUNT DECREASED AND BLOOD BILIRUBIN INCREASE. PATIENT SUBSEQUENTLY DIED (CAUSE NOT REPORTED) (B)(6) 2015. THE EVENTS WERE NOT REPORTED TO BTG BY THE INVESTIGATOR IN 2015.
Devices
| Seq | Brand | Generic | Product Code | Manufacturer | Model | Lot | UDI-DI |
|---|---|---|---|---|---|---|---|
| 445389 | THERASPHERE | YTTRIUM-90 GLASS MICROSPHERES, PRODUCT CODE: NAW | NAW | BIOCOMPATIBLES UK LTD | UNKNOWN | UNKNOWN | 05060116920284 |
Patients
| Seq | Age | Sex | Outcome | Treatment |
|---|---|---|---|---|
| 1 | 83 YR | Death| H |