MAUDE Adverse Event Report: NOVOCURE GMBH OPTUNE

Model Number TFH9100

Device Problem Adverse Event Without Identified Device or Use Problem (2993)

Patient Problem Seizures (2063)

Event Date 03/26/2018

Event Type  Injury  

Manufacturer Narrative

Novocure medical opinion is that the seizures were related to the underlying disease (anaplastic astrocytoma) and concomitant viral infection and unrelated to optune therapy.Additional risk factors for seizure in this patient include: concomitant dexamethasone (convulsion is listed as a known adverse reaction.Source: dexamethasone prescribing information).Seizures were reported as adverse events in the ef-11 pivotal phase iii recurrent gbm trial in both arms of the trial (9% and 4% in optune therapy and chemotherapy arms respectively).None of these seizures were considered device or chemotherapy related by investigators.Seizures are a common sequela of pediatric brain tumors, with an incidence of 34% reported in the literature (world neurosurg.2018, 109:e594-e600).

Event Description

A (b)(6) year old female patient with anaplastic astrocytoma began optune therapy on (b)(6) 2018, as part of the investigator sponsored trial (ist) "feasibility trial of optune for children with recurrent or progressive supratentorial high-grade glioma and ependymoma".On (b)(6) 2018, novocure was informed that the patient had experienced increased seizure activity while on optune therapy.Per hospital summary, on (b)(6) 2018, the patient presented to the emergency department (ed) with a two day history of increased seizure activity (>40/day), a sore throat, and decreased oral intake.Patient had a history of seizures and was on levetiracetam (1500 mg bid) at the time of the event.Seizure baseline was approximately 10 seizure episodes per day lasting 5-10 seconds without loss of consciousness and ending without intervention, leading to a period of drowsiness and mild altered mental status.Patient was admitted for observation and optune therapy was intermittently used during the hospital stay.Head ct was negative for ventriculoperitoneal (vp) shunt malfunction and negative for increased mass effect.Patient was loaded with fosphenytoin (1000 mg) and regular night time dose of levetiracetam (1500 mg).On (b)(6) 2018, electroencephalogram (eeg) showed sub-clinical seizures despite a second dose of fosphenytoin (1000 mg) plus two loading doses of phenobarbitone, six hours apart.Patient was continued on home dose levetiracetam and oxcarbazepine was added.On (b)(6) 2018, patient was transferred to the pediatric intensive care unit (picu) due to increased sedation secondary to anti-epileptics and hypoxia.Patient had been stable on room air on admission but became hypoxic.Patient was placed on 3/4 l of oxygen with continued hypoxia and then 2 l oxygen to keep spo2 above 90%.Due to continued de-saturation in the upper 80s, patient was placed on 6 l of supplemental oxygen by face mask and eventually weaned to.05 l nasal cannula.Stat chest x-ray revealed patchy left opacity with atelectasis.Deep suctioning was continued due to secretions.Repeat eeg showed slow wave pattern but no seizure activity.Oxcarbazepine was discontinued.Repeat ct scan showed extensive bilateral tumor involvement, vp shunt in place, ventricles not enlarged, reduction in left frontal horn, right frontal horn stable (no change compared to brain mri dated (b)(6) 2018).Dexamethasone dose was increased to 2 mg bid from 0.5 m qd.Patient was monitored clinically for signs and symptoms of infection.Patient became febrile on (b)(6) 2018, with temperature of 38.3c.Arp-pcr was positive for rhinovirus and enterovirus.Blood culture was obtained and patient received a dose of antibiotic (ceftriaxone).However, the fever was believed to be related to viral infection so antibiotics were not continued.Patient had been hemodynamically stable on admission but became tachycardic with heart rate in the 180s, which was associated with episodes of fever.Heart rate slowed to 150 after receiving iv acetaminophen.On (b)(6) 2018, patient was functioning at baseline neurologically and was transferred back to the floor from the picu.Patient was not administered any further anti-seizure medications.Patient was weaned to room air with spo2 in the mid to upper 90s.On (b)(6) 2018, the patient was discharged home in stable condition with improved seizure and neurological activity.Patient resumed optune therapy on (b)(6) 2018.Per the prescriber/ist sub-investigator, the seizures were probably related to viral upper respiratory infection and underlying disease and possibly related to optune therapy.However, the ist lead investigator assessed the seizures as not related to optune therapy.

Manufacturer Narrative

On december 23, 2021, novocure discovered that the initial submitted medical device report had a typo in the model number for the optune device in section d4-suspect medical device model number.Corrected model number is tfh9100.

• Brand Name: OPTUNE
• Type of Device: OPTUNE
• Manufacturer (Section D): NOVOCURE GMBH; business village d4; park 6/platz 10; root d4, 6039 ; SZ 6039
• Manufacturer (Section G): NOVOCURE GMBH; business village d4; park 6/platz 10; root d4, 6039 ; SZ 6039
• Manufacturer Contact: sharon perez ; 195 commerce way; hacarmel 4th floor; portsmouth, NH 03801 ; 2077527602
• MDR Report Key: 7469207
• MDR Text Key: 106837485
• Report Number: 3009453079-2018-00097
• Device Sequence Number: 1
• Product Code: NZK
• Combination Product (y/n): N
• Reporter Country Code: US
• PMA/PMN Number: P100034
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: Health Professional
• Reporter Occupation: Physician
• Type of Report: Initial,Followup
• Report Date: 01/07/2022

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
• Device Operator: Lay User/Patient
• Device Model Number: TFH9100
• Device Catalogue Number: N/A
• Device Lot Number: N/A
• Was Device Available for Evaluation?: No
• Is the Reporter a Health Professional?: Yes
• Was the Report Sent to FDA?: No
• Device Age: 21 MO
• Initial Date Manufacturer Received: 04/03/2018
• Initial Date FDA Received: 04/27/2018
• Supplement Dates Manufacturer Received: 12/23/2021
• Supplement Dates FDA Received: 01/07/2022
• Was Device Evaluated by Manufacturer?: Device Not Returned to Manufacturer
• Date Device Manufactured: 07/13/2016
• Is the Device Single Use?: No
• Is This a Reprocessed and Reused Single-Use Device?: No
• Type of Device Usage: Reuse
• Patient Sequence Number: 1
• Treatment: DEXAMETHASONE.; FAMOTIDINE.; LEVETIRACETAM.; SULFAMETHOXAZOLE/TRIMETHOPRIM.
• Patient Outcome(s): Hospitalization
• Patient Age: 10 YR
• Patient Sex: Female
• Patient Weight: 50 KG
• Patient Ethnicity: Hispanic