MAUDE Adverse Event Report: COOK IRELAND LTD ZILVER PTX 35 DRUG-ELUTING STENT; NIU STENT, SUPERFICIAL FEMORAL ARTERY, DRUG-ELUTING

Model Number G24890

Device Problem Occlusion Within Device (1423)

Patient Problem Reocclusion (1985)

Event Date 12/13/2017

Event Type  Injury  

Manufacturer Narrative

(b)(4).Device evaluation: the device was implanted in the patient and is therefore unavailable for evaluation.With the information provided a document based investigation was carried out.The patient had the following pre-existing conditions: this (b)(6)-year-old female presented at the time of enrollment with a history of hypertension and smoking (current).The lesion morphology revealed a tasc i type c lesion and a tasc ii type b lesion with thrombus and mild calcification.There was no previous intervention in the study lesion.There was no inflow tract stenosis greater than 50% and there were three patent runoff vessels.Baseline angiographic lesion measurements revealed a proximal reference vessel diameter (rvd) of 5 mm and distal rvd of 5 mm.There was 100% diameter stenosis.The lesion length was 55.0 mm.There is no evidence to suggest that this event did not occur, therefore the complaint is confirmed based on customer testimony.Images were provided to support the complaint investigation.They were reviewed through cook research inc.(cri) and the following comments were provided by the independent reviewer: findings: pre-implantation and implantation angiography is provided.Post-implantation six, 12, and 24 month ultrasounds are provided.Six and 24 month plain films are provided.A 24 month abi is provided.Imaging of the complaint reported at three years was not provided.The stent was implanted across a distal right superficial femoral artery into an above the knee, popliteal artery occlusion.The stenosis was completely relieved.The stent extended 1cm inferior to the femoral epicondyles.In the proximal, mid, and distal sfa, angiographic 50% stenoses superimposed on diffuse atherosclerotic irregularity were left untreated.The proximal and mid stenoses were likely greater than 50% because enface plaque was evident at these stenoses.On all three follow up ultrasounds, these stenoses demonstrated peak to baseline systolic velocity ratios greater than 2:1, consistent with 50-99% stenosis.Between six months and one year, new flow reversal in the right anterior tibial artery on ultrasound indicated proximal anterior tibial artery occlusion.Since the abis depended on the status of the posterior tibial artery, this did not degrade the right abi.Stability of the right abi though two years indicated stable atherosclerotic disease from the right iliac arteries through the posterior tibial artery, including the diseased sfa and the stent.The bent knee x-ray performed at 24 months demonstrated transient stent element distortion at the femoral epicondyles, consistent with kinking and/ or twisting.On ultrasound, in-stent and adjacent artery stenosis was not observed.Impression: stent occlusion cannot be confirmed as imaging from the complaint event was not provided.The stent remained widely patent through two years despite significant untreated upstream sfa stenoses, reported continued tobacco abuse, and stent kinking with knee flexion.The observed kink with knee flexion where the stent passed the level of the femoral epicondyles risked stent thrombosis.Although atherosclerotic disease progression in the sfa and in-stent stenosis through two years was immeasurable by abi and ultrasound, slow progression was certain given the continued tobacco abuse.Their progression would decrease the duration and/ or degree of knee flexion required to thrombose the stent.This explains how the stent, after remaining free of in-stent stenosis for two years, could suddenly occlude at year three.Significant findings relative to the patient's anatomy were not observed.Significant findings relative to the disease state were observed.Persistent tobacco abuse was reported.Significant inflow limitation from sfa atherosclerotic disease limited inflow.Significant findings relative to the use of the device were observed.Stent implantation inferior to the femoral epicondyles subjected the stent to kinking with knee flexion.Inflow limitation from upstream sfa stenoses was left untreated.Significant findings relative to the design or performance of the device were not observed.Cause of adverse events was not observed.Following the receipt of imaging review, it was noted that imaging from the date of the complaint reported, i.E.(b)(4) 2017 was not covered in the review.It was determined that this imaging has now been received by cri and an updated version of the review is currently pending.The investigation will be updated once this is received.It may be noted that stent kinking due to knee flexing was noted in the imaging review.A separate complaint file has been opened to capture this event.For details of the investigation reference complaint file (b)(4).Restenosis is a common adverse event of endovascular procedures and can be caused by injury to the vessel (e.G.During percutaneous transluminal angioplasty (pta) and/or stenting).Vessel injury provokes an inflammatory response that leads to (or amplifies) the restenosis process.It may be noted that surface of the zilver ptx stent is coated with the drug (paclitaxel) to help prevent subsequent restenosis of the artery.It can be therefore stated that it is very unlikely that the reported restenosis could have occurred due to zilver ptx malfunction; however as no imaging was available at the time of investigation, a definitive root cause of this event cannot be determined at this time.It may be noted that as per the instructions for use, restenosis of the stented artery is a known potential adverse event associated with the placement of this device.Document review: the ziv6-35-125-6-80-ptx stent contains zilver ptx drug eluting stent zvsp6-125-6-80-is.Prior to distribution all zilver ptx devices are subject to visual inspection and functional checks to ensure device integrity.A review of the relevant manufacturing records revealed no discrepancies that could have contributed to this complaint.Upon review of complaints, this failure mode has not occurred previously.Based on the information available to date, there is no evidence to suggest that there are any manufacturing issues associated.Summary: there is no evidence to suggest that this event did not occur, therefore the complaint is confirmed based on customer testimony.Thrombolysis & angioplasty were performed as a result of this occurrence.The patient remains in the study.Complaints of this nature will continue to be monitored for any potential emerging trends.

Event Description

Occlusion/restenosis definitely related to study product.At the index procedure on (b)(6) 2014, the patient received one 6 mm x 80 mm zilver ptx study stent in the right popliteal artery.On (b)(6) 2014, the patient underwent pre-dilatation of study lesion with one inflation of a 5.0 x 80 mm balloon at 6 atm for 45 seconds and a second inflation at 5 atm for 60 seconds.One 6.0 mm x 80 mm study stent was placed in the popliteal artery via contralateral access.The implanting physician noted that device deployment was easy.No non-study stents were used to treat the study lesion.Post-stent dilatation was performed with two inflations of a 5.0 mm x 80 mm balloon at 4 atm for 15 seconds and 10 atm for 10 seconds.At the conclusion of the case, thrombus was present and was treated.There was no dissection noted by the site, and the entire length of the study stent was apposed to the vessel wall.There was 10 % residual stenosis remaining in the study lesion.The proximal and distal rvds were 5.0 mm.The post-procedural abi was 0.93 for the study leg.On the same day, the patient was discharged from the hospital taking aspirin and plavix.On (b)(6) 2017 (1433 days post-procedure), the patient experienced an occlusion/restenosis of the study lesion (and proximal to the study lesion) requiring intervention.The patient had continued to take aspirin.Thrombolysis was performed on (b)(6) 2017 and angioplasty was done on (b)(6) 2017.The physician determined that the occlusion/ restenosis of the study lesion was definitely related to the study product and not related to the study procedure.To the question, ¿did the device malfunction or deteriorate in characteristics or performance?¿, the investigator marked no.

Manufacturer Narrative

(b)(4).Exemption number: e2016031.(b)(4).The device was implanted in the patient and is therefore unavailable for evaluation.With the information provided a document based investigation was carried out.The patient had the following pre-existing conditions: this (b)(6) female presented at the time of enrollment with a history of hypertension and smoking (current).The lesion morphology revealed a tasc i type c lesion and a tasc ii type b lesion with thrombus and mild calcification.There was no previous intervention in the study lesion.There was no inflow tract stenosis greater than 50% and there were three patent runoff vessels.Baseline angiographic lesion measurements revealed a proximal reference vessel diameter (rvd) of 5 mm and distal rvd of 5 mm.There was 100% diameter stenosis.The lesion length was 55.0 mm.There is no evidence to suggest that this event did not occur, therefore the complaint is confirmed based on customer testimony.Images were provided to support the complaint investigation.They were reviewed through cook research inc.(cri) and the following comments were provided by the independent reviewer: findings: 1.Pre-implantation and implantation angiography are provided.Post-implantation six, 12, and 24 month ultrasounds are provided.Six and 24 month plain films are provided.A 24 month abi is provided.Imaging of the complaint reported at three years was provided.2.The stent was implanted across a distal right superficial femoral artery into an above the knee popliteal artery occlusion.The stenosis was completely relieved.The stent extended 1 cm inferior to the femoral epicondyles.3.In the proximal, mid, and distal sfa, angiographic 50% stenoses superimposed on diffuse atherosclerotic irregularity were left untreated.The proximal and mid stenoses were likely greater than 50% because enface plaque was evident at these stenoses.On all three follow up ultrasounds, these stenoses demonstrated peak to baseline systolic velocity ratios greater than 2:1, consistent with 50-99% stenosis.4.Between six months and one year, new flow reversal in the right anterior tibial artery on ultrasound indicated proximal anterior tibial artery occlusion.Since the abis depended on the status of the posterior tibial artery, this did not degrade the right abi.Stability of the right abi through two years indicated stable atherosclerotic disease from the right iliac arteries through the posterior tibial artery, including the diseased sfa and the stent.5.The bent knee x-ray performed at 24 months demonstrated transient stent element distortion at the femoral epicondyles, consistent with kinking and/ or twisting.6.On ultrasound, in-stent and adjacent artery stenosis was not observed.7.Angiography at approximately two years was reported as unscheduled.Study stent angioplasty followed diagnostic angiography and overnight thrombolysis.The unscheduled presentation and prompt treatment indicate that although underlying lesions may have been present, an acute thrombosis was the primary event.8.The stent and a short segment of sfa proximal to the stent were occluded.Overnight thrombolysis and subsequent drug coated balloon (dcb) angioplasty indicated that the occlusion was all clot except for a focal, moderate to severe, 50-75%, distal in-stent stenosis from neointimal hyperplasia.This stenosis developed exactly where knee flexion kinked the stent.9.A less than 50% distal sfa stenosis at implantation had progressed to greater than 75%.One of the previously imaged mid sfa stenosis that initially appeared angiographically moderate but was more severe on ultrasound also progressed to 60%.Because the plaque was still primarily enface, the stenosis was likely more severe than it appeared.10.The proximal sfa stenosis was stable.11.Anterior tibial artery occlusion as suspected by ultrasound was confirmed.12.The sfa stenoses and distal stent neointimal hyperplasia were relieved with dcb angioplasty following thrombolysis.13.Follow up ultrasound one week after the secondary intervention demonstrated continued resolution of the sfa and in-stent stenoses.Impression: 1.The primarily thrombotic stent occlusion was secondary to knee flexion precipitated thrombosis of neointimal hyperplasia in the distal stent and progressive inflow limitation from proximal sfa stenoses.These processes were aggravated by continued tobacco abuse.2.The neointimal hyperplasia occurred where knee flexion transiently kinked the stent.The following queries were sent to the independent reviewer on receipt of the imaging review: ¿the stent and a short segment of sfa proximal to the stent were occluded.Overnight thrombolysis and subsequent drug coated balloon (dcb) angioplasty indicated that the occlusion was all clot except for a focal, moderate to severe, 50-75%, distal in-stent stenosis from neointimal hyperplasia.This stenosis developed exactly where knee flexion kinked the stent.¿ was the occlusion a mix of both thrombosis and restenosis? and if so were they related to each other and as a result of the stent kinking? ¿11.Anterior tibial artery occlusion as suspected by ultrasound was confirmed.¿ ¿ was this related to the zilver ptx stent? if so what was the nature of the occlusion? the following was received: ¿the occlusion was primarily thrombosis with some restenosis where the stent kinked and or twisted with knee flexion.There was not nearly enough neointimal hyperplasia to occlude the stent.The stent need some transient event to cause it to clot.Knee flexion is the usual cause of this particularly with lower sfa popliteal stent such as this.However because it went for a long time without a problem knee flexion alone could have not been the sole cause.Knee flexion can cause neointimal hyperplasia.The neointimal hyperplasia was exactly were sent deformed on x-ray.Although it cannot be determined kinking and twisting were likely both present.After three years enough neointimal hyperplasia had built up inside the stent that when the knee was flexed, the lumen was just not narrowed but completely occluded.This is the most plausible explanation for primary thrombosis of a stent three years after implantation with just one focus of moderate to severe restenosis that also matched where the stent had previously been shown to twist and kink.The anterior tibial artery occlusion predated the occlusion and was consequently unrelated to the stent occlusion.It was a sign of progressive atherosclerotic disease and outflow limitation that could have a deleterious effect on stent patency in that the patient went from having two vessel to one vessel runoff.¿ the customer complaint is confirmed as the failure was verified on the imaging review received.The occlusion was primarily thrombosis with some restenosis where the stent kinked and or twisted with knee flexion.As stated in the imaging review, the primarily thrombotic stent occlusion was secondary to knee flexion precipitated thrombosis of neointimal hyperplasia in the distal stent and progressive inflow limitation from proximal sfa stenoses.These processes were aggravated by continued tobacco abuse.It may be noted that as per the instructions for use, thrombosis of the stented artery is a known potential adverse event associated with the placement of this device.Prior to distribution all zilver ptx devices are subject to visual inspection and functional checks to ensure device integrity.A review of the relevant manufacturing records revealed no discrepancies that could have contributed to this complaint.Upon review of complaints, this failure mode has not occurred previously with the lot number c950186.Based on the information available to date, there is no evidence to suggest that there are any manufacturing issues associated with the lot number c950186.Thrombolysis & angioplasty were performed as a result of this occurrence.The patient remains in the study.Complaints of this nature will continue to be monitored for any potential emerging trends.

Event Description

This follow up mdr is being submitted due to the receipt and review of updated images relating to this event.Initial report details: occlusion/restenosis definitely related to study product at the index procedure on (b)(6) 2014, the patient received one 6 mm x 80 mm zilver ptx study stent in the right popliteal artery.On (b)(6) 2014, the patient underwent pre-dilatation of study lesion with one inflation of a 5.0 x 80 mm balloon at 6 atm for 45 seconds and a second inflation at 5 atm for 60 seconds.One 6.0 mm x 80 mm study stent was placed in the popliteal artery via contralateral access.The implanting physician noted that device deployment was easy.No non-study stents were used to treat the study lesion.Post-stent dilatation was performed with two inflations of a 5.0 mm x 80 mm balloon at 4 atm for 15 seconds and 10 atm for 10 seconds.At the conclusion of the case, thrombus was present and was treated.There was no dissection noted by the site, and the entire length of the study stent was apposed to the vessel wall.There was 10 % residual stenosis remaining in the study lesion.The proximal and distal rvds were 5.0 mm.The post-procedural abi was 0.93 for the study leg.On the same day, the patient was discharged from the hospital taking aspirin and plavix.On (b)(6) 2017 (1433 days post-procedure), the patient experienced an occlusion/restenosis of the study lesion (and proximal to the study lesion) requiring intervention.The patient had continued to take aspirin.Thrombolysis was performed on (b)(6) 2017 and angioplasty was done on (b)(6) 2017.The physician determined that the occlusion/restenosis of the study lesion was definitely related to the study product and not related to the study procedure.To the question, ¿did the device malfunction or deteriorate in characteristics or performance?¿, the investigator marked no.

• Brand Name: ZILVER PTX 35 DRUG-ELUTING STENT
• Type of Device: NIU STENT, SUPERFICIAL FEMORAL ARTERY, DRUG-ELUTING
• Manufacturer (Section D): COOK IRELAND LTD; o halloran road; limerick
• MDR Report Key: 7189303
• MDR Text Key: 97396908
• Report Number: 3001845648-2018-00021
• Device Sequence Number: 1
• Product Code: NIU
• UDI-Device Identifier: 10827002248905
• UDI-Public: (01)10827002248905(17)140304(10)C950186
• Combination Product (y/n): N
• PMA/PMN Number: P100022
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: company representative,health
• Type of Report: Initial,Followup
• Report Date: 01/15/2018

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 01/15/2018
• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: No
• Device Operator: Health Professional
• Device Model Number: G24890
• Device Catalogue Number: ZIV6-35-125-6-80-PTX
• Was Device Available for Evaluation?: No
• Was the Report Sent to FDA?: No
• Distributor Facility Aware Date: 12/19/2017
• Event Location: Hospital
• Date Manufacturer Received: 01/15/2018
• Is This a Reprocessed and Reused Single-Use Device?: No
• Patient Sequence Number: 1
• Patient Outcome(s): Required Intervention
• Patient Age: 70 YR