Age: 39.0
Sex: M
Vaccine: ANTH
Symptoms: Death, Drug abuser, Drug screen negative, Hepatitis, Hypertension
Clinical narrative: Information was received on 04JAN2017, 09JAN2017, 10JAN2017 and 13JAN2017 from GlaxoSmithKline (GSK) in the form of a blinded CIOMS report. GSK physician indicated the study drug was unblinded and subject received ava (lot FAV634) only and did not receive raxibacumab. Death secondary to combined fentanyl and methamphetamine intoxication. This male subject was enrolled in a blinded GSK study. The subject received ava vs ava+raxibacumab+diphenhydramine from 29th July 2016 as a study participant. The subject's past medical history included tonsillitis, tonsillectomy, removal of wisdom teeth and impacted wisdom tooth. On 24th September 2016, 57 days after the first dose of ava (lot FAV634) vs ava+raxibacumab+diphenhydramine, the subject developed grade 4 unknown cause of death. Serious criteria included death and medically significant. The outcome of unknown cause of death was fatal on 24th September 2016. The reported cause of death was unknown cause of death. The GSK investigator considered that there was no reasonable possibility that the unknown cause of death may have been caused by ava vs ava+raxibacumab+diphenhydramine. Additional information: GSK study site called subject on 27Sep2016 because he had not come to the site for his Day 29 appointment and was notified by the subject's parent that he was found dead at home on 24Sep2016. Cause of death was unknown at this time. The subject had no medical history of angina pectoris, myocardial infarction, stroke, diabetes, hypertension and hyperlipidemia. Follow-up information received by GSK on 24th October 2016: The subject was a male in his late 30's. Follow up information received by GSK on 01 November 2016: An autopsy was scheduled to be performed. Follow-up information received by GSK on 09 December 2016: On 24th September 2016, 57 days after the first dose of ava vs ava+raxibacumab+diphenhydramine, the subject developed grade 4 drug intoxication (combined fentanyl and methamphetamine intoxication). Serious criteria included death. The subject died on 24th September 2016. The investigator considered that there was no reasonable possibility that the drug intoxication may have been caused by ava vs ava+raxibacumab+diphenhydramine. GSK study site investigator text: autopsy showed evidence of chronic alcohol abuse and hypertensive cardiovascular disease, which significantly contributed to death. Autopsy revealed an enlarged (dilated) heart due to repeated alcoholic toxicity related to alcohol abuse. Long-standing high blood pressure, as evidenced by microvascular disease in the brain and kidney, also contributed to the enlargement of the heart. Autopsy report was reviewed by GSK on 09-Dec-2016 and the SAE information was updated. In addition to the autopsy finding, relevant diagnostic test results noted "there were findings of chronic intravenous drug abuse including needle tracks, inflammation and scarring of the liver, and injected foreign material within the lungs, liver and spleen. Toxicologic analysis of post-mortem femoral blood revealed a toxic concentration of fentanyl. Methamphetamine, amphetamine, norfentanyl, and cotinine were also detected. Analysis of the vitreous fluid for electrolytes was unremarkable". The report also noted that "enlarged hearts are pathologic, prone to electrical instability and sudden cardiac arrest, and less tolerant of the combined toxicity of fentanyl and methamphetamine". It should be noted that the subject did not report any history of hypertension to the study site. Additionally, the subject's urine drug screen results at screening were negative.