Intrathecal Drug Delivery Systems

Study Participants

Centers

The following tables and graphs were generated based on data collected between the date of initiation of the Implantable Systems Performance Registry (ISPR) for intrathecal drug delivery systems on August 7, 2003 and the report cut-off date of July 29, 2011. Fifty centers enrolled and contributed patients to the intrathecal drug delivery systems section of the report.

Patients

As the table below demonstrates, there were 4,891 total intrathecal drug delivery system patients enrolled in the ISPR through July 29, 2011. As indicated, 52.6% of patients were implanted with an intrathecal drug delivery system for treatment of non-malignant pain (pain not related to cancer and its treatment), followed by 27.1% for treatment of intractable spasticity, and 19.6% for treatment of malignant pain (pain related to cancer). For the most part, the ISPR is representative of the overall population of patients receiving new pump implants in the United States, with the minor exception of malignant pain, which is slightly over-representative in the ISPR (ISPR = 19.6% versus U.S. population = 14.3%).

Event Summary

There were 2,701 events reported between August 2003 and July 29, 2011 in patients with intrathecal drug delivery systems. Nineteen percent of these events (505/2,701) were categorized as product performance-related events and are presented graphically within this report. In addition, there were 1,164 non-product performance events and 1,032 deaths reported during this timeframe. Early versions of the protocol required events to be reported only when the event required a surgical intervention, resulted in therapy abandonment, or resulted in death. The required event reporting definition was expanded in April 2010 to include all adverse events related to the device, implant procedure, and/or therapy. The event tables provided below include combined data from these versions of the protocol.

^a Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term or Lower Level Term
^b The total number of patients with event may not represent the sum of all rows, as a patient may have experienced more than one type of event.
^c Includes 13 events reported as pump connector break/cut , 4 events reported as pump malfunction, 1 pump unable to interrogate/program, 1 possible corrosion of pump, 1 inconsistent pump reservoir volume, 1 telemetry stopped secondary to error code, 1 discrepancy in reservoir volume, 1 leak at pump connector, and 1 pump residual volume
^d Includes 11 events reported as catheter malfunction, 2 coiled catheters, 1 suspected catheter failure, 1 difficulty aspirating catheter, 1 catheter wear, 1 patency issue with catheter, 1 catheter aneurysm, and 1 catheter arachnoid loculations caused by the catheter
^e Event was reported by the physician as being caused by the catheter, but no device event was provided at the time of data cut-off
^f Physician reported patient was under-medicated secondary to pump-related issue

A total of 415 (82.2%) of the 505 product performance events were related to the catheter, 83 (16.4%) were related to the pump, 1 (0.2%) was related to incisional site/device tract, 1 (0.2%) was related to medication, 3 (0.6%) were reported as "other" etiology, and 2 (0.4%) did not have a specified etiology.

^a MedDRA Preferred Term
^b For products that are returned with a suspected device issue, and RPA establishes a root cause or finds no anomaly, results reported herein default to the RPA finding
^c Includes 2 events reported as unable to fill/refill pump not caused by the pump, 1 pump dislodged from sutures, 1 protrusion of pump, 1 vascular runoff of intrathecal catheter, 1 empty pump reservoir secondary to patient failure to keep refill appointments, 1 patient unable to adequately dose with baclofen not caused by the pump, and 1 suspected malfunction not yet related to a specific device
^d Composed of 75 event codes that include less than 5 patients each and events that had not been MedDRA coded at the time of the report cut-off (n=15)

There were 1,032 deaths reported in the ISPR for patients with intrathecal drug delivery systems, none of which were reported as a direct result of a device-related event or the infusion therapy. As indicated, 68.4% of patient deaths occurred in patients receiving therapy for malignant pain, 22.8% for non-malignant pain, and 8.7% for intractable spasticity.

Pumps

From August 2003 to the report cut-off date of July 29, 2011, 5,562 pumps were followed in the Implantable Systems Performance Registry (ISPR). The difference between the total number of patients (n=4,891) versus pumps is due to the fact that some patients were subsequently re-implanted with a pump multiple times.

Most of the pumps followed in the registry were either SynchroMed EL (21.5%) or SynchroMed II (78.4%), and a small number of pumps were SynchroMed Classic (0.1%). The aggregate total prospective follow-up time for all pumps was 138,494 months (11,541 years).

Pump Survival CurvesPump Survival Curves

The figures and tables below represent pump survival and 95% confidence intervals where at least 20 pumps contributed to each 3-month interval. At 3 years of follow-up, the 95% confidence intervals for the SynchroMed EL and both SynchroMed II pumps do not overlap. In addition, 95% confidence intervals for the SynchroMed EL and SynchroMed II 40 ml pumps do not overlap at 4 years of follow-up indicating that survival from pump-related events is statistically significantly better for applicable SynchroMed II pumps than SynchroMed EL pumps at these time points. Medtronic chose to voluntarily discontinue the SynchroMed EL pump in August 2007 in the United States based on broad customer acceptance of the SynchroMed II pump for all approved indications, the high reliability record of the SynchroMed II pump, and the fact that the SynchroMed II pump offers additional performance features beyond those available in the SynchroMed EL pump.

                 

Choose a model --Model 8627-18 SynchroMed EL 18mL --Model 8637-20 SynchroMed II 20mL --Model 8637-40 SynchroMed II 40mL

Model 8627-18 SynchroMed EL 18mL: Device Survival Probability

Data are shown if there are at least 20 devices in each 3-month interval.

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Pump Characteristics
Model Name	SynchroMed EL (18 mL)
FDA Approval Date	Mar 1999
Pumps Enrolled	1,162
Pumps Currently Active in Study	38
Device Events	39
Cumulative Months of Follow-up	36,444

Pump Event	Total
Motor stall	14
Motor gear corrosion	14
Pump underinfusion	7
Drug-related cracked pump tube	3
Medical device complicationa	1
Total Pump Events	39

^a Reported as unable to interrogate/program pump

Time Interval	Survival	Effective Sample Size
1 yr	99.0%	216
2 yrs	97.9%	444
3 yrs	96.4%	652
4 yrs	95.3%	668
5 yrs	94.0%	527
6 yrs	92.5%	294
7 yrs	91.5%	122
8 yrs	91.5%	42
at 102 mo	91.5%	20

 

Model 8627-18 SynchroMed EL 18mL: Specifications

Expected battery life	3-7 years
Thickness	1.08 in (27.5 mm)
Diameter (with integral access port)	3.35 in (85.2 mm)
Capacity	18.0 mL
Minimal Flow Rate*	0.048 mL/day
Maximum Flow Rate**	21.6 mL/day

* At rates less than 0.048 mL/day, the flow accuracy may exceed the ± 15% specification.
** Actual limits depend on pump calibration constant and selected infusion mode. The programmer may further narrow these limits.

Model 8637-20 SynchroMed II 20mL: Device Survival Probability

Data are shown if there are at least 20 devices in each 3-month interval.

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Pump Characteristics
Model Name	SynchroMed II (20 mL)
FDA Approval Date	Sep 2003
Pumps Enrolled	1,615
Pumps Currently Active in Study	899
Device Events	16
Cumulative Months of Follow-up	43,446

Pump Event	Total
Motor stall	8
Medical device complicationa	3
Pump no infusion	2
Hole in pump tube	1
Resonator cracked – alarm anomaly	1
Not coded	1
Total Pump Events	16

^a Includes 1 event reported as pump malfunction, 1 inconsistent pump reservoir volume, and 1 discrepancy in reservoir volume

Time Interval	Survival	Effective Sample Size
1 yr	100.0%	1,117
2 yrs	99.7%	865
3 yrs	99.3%	576
4 yrs	97.5%	356
5 yrs	96.5%	170
6 yrs	96.5%	59
at 75 mo	96.5%	36

 

Model 8637-20 SynchroMed II 20mL: Specifications

Expected battery life*	6-7 years
Thickness	0.78 in (19.5 mm)
Diameter	3.4 in (87.5 mm)
Capacity	20.0 mL
Minimal Flow Rate**	0.048 mL/day
Maximum Flow Rate**	24 mL/day

* Dependent on flow rate
** Actual limits depend on pump calibration constant and selected infusion mode.

Model 8637-40 SynchroMed II 40mL: Device Survival Probability

Data are shown if there are at least 20 devices in each 3-month interval.

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Pump Characteristics
Model Name	SynchroMed II (40 mL)
FDA Approval Date	Sep 2003
Pumps Enrolled	2,747
Pumps Currently Active in Study	1,050
Device Events	20
Cumulative Months of Follow-up	54,670

Pump Event	Total
Motor stall	10
Pump underinfusion	3
Reduced battery performance	3
Pump no infusion	2
Medical device complicationa	1
Therapeutic product ineffective	1
Total Pump Events	20

^a Reported as pump malfunction

Time Interval	Survival	Effective Sample Size
1 yr	99.9%	1,523
2 yrs	99.5%	1,057
3 yrs	99.2%	657
4 yrs	98.7%	359
5 yrs	96.0%	138
6 yrs	92.4%	35

 

Model 8637-40 SynchroMed II 40mL: Specifications

Expected battery life*	6-7 years
Thickness	1.0 in (26 mm)
Diameter	3.4 in (87.5 mm)
Capacity	40.0 mL
Minimal Flow Rate**	0.048 mL/day
Maximum Flow Rate**	24 mL/day

* Dependent on flow rate
** Actual limits depend on pump calibration constant and selected infusion mode.

Catheters

From August 2003 to the report cut-off date of July 29, 2011, 5,283 catheters were followed in the Implantable Systems Performance Registry (ISPR). The total number of catheters was not equal to the total number of pumps (n=5,562) because a patient may have undergone a pump replacement but used the same catheter, or patients may have been implanted with Medtronic pumps and non-Medtronic catheters which were not registered with Medtronic Device and Registrant Tracking system (DART). The aggregate total prospective follow-up time for all catheters was 145,282 months (12,107 years).

A total of 48.8% of the catheters were Model 8709 catheters, 13.1% were Model 8709SC catheters, 10.8% were Model 8711 catheters, 9.0% were Model 8731 catheters, 3.5% were Model 8703W catheters, 1.9% were Model 8731SC catheters, and 0.8% were other or unspecified catheters. An additional 2.2% were considered catheters revised as designed, (8731 catheters that had been repaired with an 8596 proximal or 8598 distal revision kit); 5.6% were considered catheters revised not as designed (Medtronic non-8731 catheters that had been repaired with an 8596 proximal or 8598 distal revision kit); and 4.2% were catheters grafted not as designed (catheters that involve the ad-hoc assembly of components other than a Medtronic repair kit or brand new catheter).

Catheter Survival CurvesCatheter Survival Curves

The figures and tables below represent catheter survival and 95% confidence intervals where at least 20 catheters contributed to each 3-month interval. Currently, the 95% confidence intervals for all catheter models overlap at all time intervals, indicating that survival from catheter-related events is not significantly different between the catheter models across various applicable follow-up time points.

Although not statistically significantly different, the survival estimates indicate that the survival of catheters revised not as designed (Medtronic non-8731 catheters that had been repaired with an 8596 proximal or 8598 distal revision kit) and catheters grafted not as designed (those catheters repaired or spliced using non-Medtronic components, or Medtronic components other than the Model 8596 or 8598 revision kits) have a lower probability of survival during the first 4 years of follow-up than any other catheter model, including catheters revised as designed. Medtronic catheter repair kits and 2-piece catheters include specially designed connector pins and strain relief sleeves to splice the catheter segments together. Catheters grafted not as designed, by definition, involve the ad-hoc assembly of components other than a Medtronic repair kit or brand new catheter. Explanations for this finding remain speculative, and include small sample size and a relatively brief observation period compared to other catheter models. Other non-statistical explanations may include device-related causes and/or system troubleshooting errors. Another possible explanation is that intrathecal drug and cerebrospinal fluid mixing or flow anomaly existed that was not corrected by assembly of a grafted not as designed catheter system. Medtronic will continue to monitor and review the performance and survival of catheters revised not as designed and catheters grafted not as designed. Medtronic recommends following the labeling for the Model 8596 and 8598 revision kits.

                 

Choose a model --Model 8709 --Model 8709SC --Model 8711 --Model 8731 --Model 8731SC --Revised As Designed --Revised Not As Designed --Grafted Not As Designed

Model 8709: Survival from Catheter Events

Data are shown if there are at least 20 devices in each 3-month interval.

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Catheter Characteristics
Model Number	8709
FDA Approval Date	May 1998
Catheters Enrolled	2,578
Catheters Currently Active in Study	755
Device Events	176
Cumulative Months of Follow-up	66,361

Catheter Events	Total
Catheter kink/occlusion	53
Catheter dislodgment from intrathecal space	44
Catheter break/cut	43
Medical device complicationa	10
Catheter disconnection at pump	9
Catheter disconnection at distal connection	7
Catheter related complicationb	3
Catheter leakage	3
Arachnoiditisc	1
Painc	1
Unable to enter/withdraw from catheter access port	1
Not coded	1
Total Catheter Events	176

^a Reported as pump connector break/cut
^b Includes 1 event reported as difficulty aspirating catheter, 1 catheter aneurysm, and 1 coiled catheter
^c Event was reported by the physician as being caused by the catheter, but no device event was provided at the time of data cut-off

Time Interval	Survival	Effective Sample Size
1 yr	94.4%	986
2 yrs	92.4%	894
3 yrs	90.3%	838
4 yrs	88.6%	701
5 yrs	86.9%	498
6 yrs	83.0%	380
7 yrs	81.3%	289
8 yrs	78.4%	201
9 yrs	76.3%	122
10 yrs	73.8%	77
11 yrs	73.8%	32
at 135 mo	73.8%	24

 

Model 8709: Specifications

Total Length	89 cm
Outer diameter (spinal segment)	1.4 mm (4.2 French)
Inner Diameter (spinal segment)	0.53 mm
Catheter Tip Description	Closed with 6 side holes
Catheter Volume	0.0022 mL/cm
Trimmable Segments	Pump end

Model 8709SC: Survival from Catheter Events

Data are shown if there are at least 20 devices in each 3-month interval.

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Catheter Characteristics
Model Number	8709SC
FDA Approval Date	Mar 2006
Catheters Enrolled	692
Catheters Currently Active in Study	408
Device Events	33
Cumulative Months of Follow-up	9,308

Catheter Events	Total
Catheter dislodgment from intrathecal space	10
Catheter kink/occlusion	8
Catheter break/cut	7
Catheter related complicationa	2
Catheter disconnection at distal connection	2
Catheter disconnection at pump	1
Catheter leakage	1
Unable to enter/withdraw from catheter access port	1
Medical device complicationb	1
Total Catheter Events	33

^a Includes 1 event reported as catheter arachnoid loculations caused by the catheter and 1 catheter malfunction
^b Reported as leak at pump connector

Time Interval	Survival	Effective Sample Size
1 yr	95.8%	347
2 yrs	91.9%	163
3 yrs	90.8%	60
at 42 mo	88.7%	25

 

Model 8709SC: Specifications

Total Length	89 cm
Outer diameter (spinal segment)	1.4 mm (4.2 French)
Inner Diameter (spinal segment)	0.53 mm
Catheter Tip Description	Closed tip, radiopaque, titanium with 6 side holes
Catheter Volume	0.0022 mL/cm
Trimmable Segments	Pump end

Model 8711: Survival from Catheter Events

Data are shown if there are at least 20 devices in each 3-month interval.

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Catheter Characteristics
Model Number	8711
FDA Approval Date	Oct 1999
Catheters Enrolled	573
Catheters Currently Active in Study	220
Device Events	58
Cumulative Months of Follow-up	17,640

Catheter Events	Total
Catheter kink/occlusion	22
Catheter dislodgment from intrathecal space	12
Catheter break/cut	11
Catheter related complicationa	4
Catheter disconnection at pump	2
Unable to enter/withdraw from catheter access port	2
Medical device complicationb	1
Gait disturbancec	1
Muscle spasticityc	1
Unable to withdraw fluid from catheter access port	1
Not coded	1
Total Catheter Events	58

^a Reported as catheter malfunction
^b Reported as pump connector break/cut
^c Event was reported by the physician as being caused by the catheter, but no device event was provided at the time of data cut-off

Time Interval	Survival	Effective Sample Size
1 yr	94.3%	296
2 yrs	92.5%	258
3 yrs	87.0%	203
4 yrs	84.5%	164
5 yrs	84.0%	140
6 yrs	80.4%	107
7 yrs	77.8%	82
8 yrs	74.4%	54
9 yrs	72.8%	31
at 111 mo	72.8%	24

 

Model 8711: Specifications

Total Length	104.1 cm
Outer diameter (spinal segment)	1.4 mm (4.2 French)
Inner Diameter (spinal segment)	0.53 mm
Catheter Tip Description	Closed with 6 side holes
Catheter Volume	0.0022 mL/cm
Trimmable Segments	Spinal and pump ends

Model 8731: Survival from Catheter Events

Data are shown if there are at least 20 devices in each 3-month interval.

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Catheter Characteristics
Model Number	8731
FDA Approval Date	Oct 2002
Catheters Enrolled	478
Catheters Currently Active in Study	128
Device Events	35
Cumulative Months of Follow-up	17,172

Catheter Events	Total
Catheter dislodgment from intrathecal space	16
Catheter kink/occlusion	12
Catheter related complicationa	3
Catheter disconnection at distal connection	2
Catheter break/cut	1
Medical device complicationb	1
Total Catheter Events	35

^a Includes 1 event reported as patency issue with catheter, 1 coiled catheter, and 1 catheter malfunction
^b Reported as pump connector break/cut

Time Interval	Survival	Effective Sample Size
1 yr	95.4%	291
2 yrs	93.9%	318
3 yrs	92.7%	276
4 yrs	90.8%	216
5 yrs	89.2%	141
6 yrs	85.7%	80
7 yrs	84.4%	33
at 87 mo	84.4%	24

 

Model 8731: Specifications

Total Length	104.1 cm
Outer diameter (spinal segment)	1.4 mm (4.2 French)
Inner Diameter (spinal segment)	0.53 mm
Catheter Tip Description	Closed tip, radiopaque, with 6 side holes
Catheter Volume	2.22μl/cm
Trimmable Segments	Spinal end

Model 8731SC: Survival from Catheter Events

Data are shown if there are at least 20 devices in each 3-month interval.

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Catheter Characteristics
Model Number	8731SC
FDA Approval Date	Mar 2006
Catheters Enrolled	103
Catheters Currently Active in Study	55
Device Events	5
Cumulative Months of Follow-up	1,807

Catheter Events	Total
Catheter kink/occlusion	2
Catheter dislodgment from intrathecal space	2
Catheter disconnection at distal connection	1
Total Catheter Events	5

Time Interval	Survival	Effective Sample Size
1 yr	96.3%	67
2 yrs	92.9%	34
at 30 mo	92.9%	22

 

Model 8731SC: Specifications

Total Length	104.1 cm
Outer diameter (spinal segment)	1.4 mm (4.2 French)
Inner Diameter (spinal segment)	0.53 mm
Catheter Tip Description	Closed with 6 side holes
Catheter Volume	0.0022 mL/cm
Trimmable Segments	Spinal and pump end

Revised As Designed: Survival from Catheter Events

Data are shown if there are at least 20 devices in each 3-month interval.

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Catheter Characteristics
Model Name	Revised As Designed
FDA Approval Date	Oct 2002
Catheters Enrolled	118
Catheters Currently Active in Study	41
Device Events	7
Cumulative Months of Follow-up	4,034

Catheter Events	Total
Catheter kink/occlusion	5
Catheter dislodgment from intrathecal space	1
Catheter related complicationa	1
Total Catheter Events	7

^a Reported as catheter malfunction

Time Interval	Survival	Effective Sample Size
1 yr	97.2%	69
2 yrs	94.4%	63
3 yrs	92.9%	55
4 yrs	92.9%	49
5 yrs	92.9%	38
6 yrs	88.9%	23

 

Revised As Designed: Specifications

Revised As Designed catheters are Model 8731 catheters repaired with the 8596 proximal or 8598 distal revision kit.

Revised Not As Designed: Survival from Catheter Events

Data are shown if there are at least 20 devices in each 3-month interval.

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Catheter Characteristics
Model Name	Revised Not As Designed
FDA Approval Date	NA
Catheters Enrolled	294
Catheters Currently Active in Study	153
Device Events	28
Cumulative Months of Follow-up	6,587

Catheter Events	Total
Catheter kink/occlusion	9
Catheter break/cut	8
Catheter dislodgment from intrathecal space	6
Catheter disconnection at distal connection	3
Catheter related complicationa	1
Catheter leakage	1
Total Catheter Events	28

^a Reported as catheter malfunction

Time Interval	Survival	Effective Sample Size
1 yr	91.8%	187
2 yrs	90.0%	122
3 yrs	86.1%	77
4 yrs	83.4%	44
5 yrs	80.0%	25

 

Revised Not As Designed: Specifications

Revised Not As Designed catheters are Medtronic non-8731 catheters repaired with the 8596 proximal or 8598 distal revision kit.

Grafted Not As Designed Catheters: Survival from Catheter Events

Data are shown if there are at least 20 devices in each 3-month interval.

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Catheter Characteristics
Model Name	Grafted Not As Designed
FDA Approval Date	NA
Catheters Enrolled	224
Catheters Currently Active in Study	126
Device Events	21
Cumulative Months of Follow-up	4,427

Catheter Events	Total
Catheter dislodgment from intrathecal space	9
Catheter kink/occlusion	5
Catheter break/cut	3
Catheter related complicationa	1
Catheter disconnection at pump	1
Medical device complicationb	1
Catheter leakage	1
Total Catheter Events	21

^a Reported as catheter malfunction
^b Reported as pump connector break/cut

Time Interval	Survival	Effective Sample Size
1 yr	91.1%	102
2 yrs	88.9%	65
3 yrs	85.9%	50
4 yrs	85.9%	34
at 57 mo	82.8%	21

 

Grafted Not As Designed: Specifications

Grafted Not As Designed catheters are catheters repaired or spliced using non-Medtronic components, or Medtronic components other than the Model 8596 or 8598 revision kits spliced together using existing or other industry products.