MAUDE Adverse Event Report: NOVOCURE, LTD. OPTUNE

Model Number TFH-9100

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

Patient Problems Wound Dehiscence (1154); Cerebrospinal Fluid Leakage (1772)

Event Date 11/22/2019

Event Type  Injury  

Manufacturer Narrative

Novocure's medical opinion is that cerebrospinal fistula is not related to optune therapy but is related to previous tumor resection and is a known complication of craniotomy.Cerebrospinal fistula was not reported as an adverse event in the pivotal ef-11 recurrent gbm trial or in the commercial program to date.A contribution of the array placement to wound dehiscence cannot be ruled out.Wound dehiscence was not reported as an adverse event in the pivotal ef-11 recurrent gbm trial.There have been 91 reports of wound dehiscence in the commercial program to date.Contributing factors for wound dehiscence in this patient include: concomitant dexamethasone use (impaired wound healing and increased risk of infection are listed as side effects.Source: dexamethasone prescribing information), prior radiation, underlying cancer disease and prior surgery affecting skin integrity.

Event Description

A (b)(6)-year old female patient with recurrent glioblastoma began optune therapy on (b)(6) 2018, as part of the non-interventional study "ttfields in germany in routine clinical care".On december 13, 2019, novocure was informed by the patient's spouse that the patient had been hospitalized.On (b)(6) 2019, patient presented to the emergency department with a cerebrospinal fistula of the left parietal-occipital surgical resection site (last resection (b)(6) 2019).Head mri showed serous liquid accumulations in the left parietal-temporal-occipital epidural cavity below the trepanation area, no empyema, no abscess.Lumbar drain was placed with a collection of 30 milliliters of cerebrospinal fluid daily for three days.Wound dehiscence was treated with secondary sutures.Wound was dry and not irritated.On (b)(6) 2019, lumbar drain was removed and patient was discharged home.On december 13, 2019, it was reported to novocure by the patient's spouse that the patient resumed optune therapy on (b)(6) 2019.On (b)(6) 2019, patient's sutures were removed and the wound was noted to be weeping.On (b)(6) 2019, patient presented to the neuro-surgical clinic with a cerebrospinal fluid fistula.Optune therapy was discontinued.Patient had no headaches, no nausea, no fever; leukocytes and c reactive protein were not increased.Wound was not irritated or crusted.Cerebrospinal fluid leakage was observed.Later that day, patient underwent wound revision surgery.Bone flap was removed and duraplasty with muscle and periosteum was performed.Bone edges and boreholes were filled with bone cement.After surgery, the wound was observed to be dry and not irritated, with no signs of cerebrospinal fluid leakage, no fever, no headaches, no nausea and no vomiting.On (b)(6) 2019, patient was discharged home.Per prescriber, the events were related to optune therapy.

Manufacturer Narrative

On (b)(6) 2020, novocure received additional information regarding the event.At the time of this report, the patient had not restarted optune therapy since temporary discontinuation on (b)(6), 2019.On (b)(6) 2020, during a check-up, the wound revision site was dry, not irritated, with no signs of cerebrospinal fluid (csf) leakage.On (b)(6), the patient observed discharge from the wound.On (b)(6) 2020, the patient presented to the neurosurgical emergency department with coughing and possible csf leakage.Patient denied headaches, nausea or vomiting, and vertigo.The wound was not irritated, crusted or red.C-reactive protein was 1 mg/l with a leukocyte count of 4400/mcl.Later that day, lumbar drain was placed and 40 ml csf fluid was collected daily.On (b)(6) 2020, a lumbar-peritoneal shunt was placed.After the surgery, the patient had headaches and ringing in her ears when in vertical position.On (b)(6) 2020, head ct showed no signs of over-drainage or bleeding.On (b)(6) 2020, patient was discharged home with no signs of sensor motor deficits.Wound was dry and not irritated.On (b)(6) 2020, the patient observed the wound to be weeping again.On (b)(6) 2020, the patient presented to the neurosurgical emergency department with a discrete wound dehiscence in the middle part of the parietal occipital wound.Inflammation parameters were not increased and patient did not have fever or signs of meningitis.X-ray showed correct placement of the csf shunt.On (b)(6) 2020, patient underwent surgery to retrieve the csf shunt.After cutting the end of the shunt catheter, csf, which was apparently under pressure, discharged immediately, indicating under-drainage.Wound revision was performed.After surgery, the wound was dry and not irritated, with no signs of csf leakage and no signs of over-drainage.On (b)(6) 2020, the patient was discharged home.Suture removal was planned for (b)(6) 2020.Per pre-scriber, the events were related to optune therapy.

Manufacturer Narrative

On september 07, 2020, novocure received additional information regarding the event.At the time of this report, the patient had not resumed optune therapy since discontinuation on (b)(6) 2019.On an unknown date, during a scheduled outpatient visit, the patient reported that approximately every two days, small amounts of fluid were discharged at the craniotomy incision site.On (b)(6) 2020, a head mri showed intraventricular and subgaleal air inclusions as well as suspected gbm recurrence.On (b)(6) 2020, the patient was hospitalized.At admission, patient was in good general health with no sensorimotor deficits.Patient did not demonstrate signs of meningitis or fever.The craniotomy incision appeared dry without erythema, however wound dehiscence was present.On (b)(6) 2020, a head ct demonstrated progressive air inclusions with ventricular expansion.Later that evening, patient became disorientated and confused.On (b)(6) 2020, patient underwent surgical resection for gbm recurrence and wound revision surgery.Bone flap and bone cement were removed.The dura was reopened and air was found trapped in the resection cavity.Patient's dura was reconstructed and wound was closed using rectus abdominis flap and split-thickness skin graft.Patient was transferred to the intensive care unit for further monitoring.On (b)(6) 2020, patient's transplant was under perfused and required additional wound revision surgery, without complications.On (b)(6) 2020, patient was extubated without complications, however the patient was not able to answer simple questions and was unable to move extremities upon request.Repeat head ct demonstrated improvement.Patient became restless during the night and was sedated with propofol.On (b)(6) 2020, patient's surgical incision, skin flap, and skin graft removal site appeared normal.Head and abdomen drains were removed and the patient was transferred to the general ward.On (b)(6) 2020, patient was discharged home in good general condition.Per prescribing physician, cause of the events were related to optune therapy.

Manufacturer Narrative

On november 25, 2020, novocure received additional information regarding the event.On (b)(6) 2020, during a scheduled outpatient visit, prescribing physician noted cerebrospinal fluid leakage at the dorsal caudal part of the craniotomy surgical incision site.Patient was hospitalized the same day for further evaluation.The patient presented with severe headaches accompanied by nausea with increased intensity when lying down.The patient did not demonstrate signs of meningismus or sensorimotor deficits.Testing of cranial nerves appeared normal.On (b)(6) 2020, a head ct demonstrated progressive pneumocephalus.The left parietal occipital resection defect appeared to be almost completely filled with air.The lateral ventricles as well as the third ventricle presented pneumatized.The patient was started on prophylactic antibiotics (ceftriaxone) for suspected meningitis.On (b)(6) 2020, the patient became disorientated and her vigilance appeared reduced, she was transferred to the neurosurgical intensive care unit on the same day.On (b)(6) 2020, the patient underwent surgery for skin flap revision, cranium bone flap removal, and duraplasty.The dura did not appear irritated or inflamed.The dura was sealed with fibrin adhesive.A patch of rectus abdominis fascia skin graft was placed and the skin flap altered to cover the dura over a wide area.Split skin graft from the left upper leg was placed for additional coverage and the wound was sutured closed.The patient was transferred to the neurosurgical intensive care unit.On (b)(6) 2020, the patient was extubated, appeared responsive, and able to move upon request.On an unspecified date, while in the the neurosurgical general ward, the patient experienced neck stiffness and alternating vigilance.Meningitis was suspected and patient was started on antibiotics (meropenem/vancomycin).The headaches and fever improved.Lab values did not demonstrate elevated inflammatory parameters.On (b)(6) 2020, lung x-ray showed a right pneumothorax.Thorax drain was inserted.On (b)(6) 2020, pneumothorax was completely resolved and thorax drain was removed.On (b)(6) 2020, antibiosis was stopped as crp value was constantly low.The skin flap and split skin grafts presented dry without irritation.On (b)(6) 2020, cranium sutures were removed and patient was discharged home in good general condition with instructions to wear a cranial helmet to protect the parietal occipital region where the bone flap had been removed.Per prescribing physician, the event of recurrent liquor fistula was related to optune therapy.

• Brand Name: OPTUNE
• Type of Device: OPTUNE
• Manufacturer (Section D): NOVOCURE, LTD.; 195 commerce way; portsmouth NH 03801
• MDR Report Key: 9667230
• MDR Text Key: 191558880
• Report Number: 3009453079-2020-00134
• Device Sequence Number: 1
• Product Code: NZK
• Combination Product (y/n): N
• PMA/PMN Number: P100034
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: consumer
• Type of Report: Initial,Followup,Followup,Followup
• Report Date: 12/21/2020

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: TFH-9100
• Device Catalogue Number: N/A
• Device Lot Number: N/A
• Was Device Available for Evaluation?: No
• Device Age: 10 MO
• Initial Date Manufacturer Received: 01/20/2020
• Initial Date FDA Received: 02/04/2020
• Supplement Dates Manufacturer Received: 05/06/2020; 09/07/2020; 11/25/2020
• Supplement Dates FDA Received: 06/03/2020; 10/06/2020; 12/21/2020
• Is This a Reprocessed and Reused Single-Use Device?: No
• Patient Sequence Number: 1
• Treatment: ACYCLOVIR.; AMLODIPINE.; CEFUROXIME.; CEFUROXIME.; CITALOPRAM.; DEXAMETHASONE.; DIPHENYLPROPYLAMINE.; DIPYRONE.; ENOXAPARIN.; FOLIC ACID.; HEPARIN.; IBUPROFEN.; INSULIN.; L-THYROXINE.; LETROZOLE.; LOMUSTINE.; MELPERONE HYDROCHLORIDE.; PANTOPRAZOLE.; PREDNISOLONE.; SULFAMETHOXAZOLE/TRIMETHOPRIM.; TEMOZOLOMIDE.; TILIDINE.; URAPIDIL.
• Patient Outcome(s): Hospitalization; Required Intervention
• Patient Age: 67 YR
• Patient Weight: 60