Feasibility of an Investigational Extended Wear Infusion ...
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INTRODUCTION RESULTS OBJECTIVE MATERIALS CONCLUSION Insulin Pump Therapy (IPT) is limited by 3-day maximum cannula life and reported failure rates of 15-25% SteadiFlow ™ Technology: Kinkproof, Flexible Cannula with Sideports 88% IIS (36/41) Inserted In 20 Participants Successfully Delivered Insulin For 7-Days Protocol-specified failure criteria were not well aligned with the routine practice of diabetes management No significant difference in total insulin delivered by day was observed, although a subset of participants did increase use SteadiFlow cannula is safe and well tolerated Evaluate the feasibility and device performance of a prototype cannula for an extended wear infusion set Infusion set with SteadiFlow ™ cannula technology (Capillary Biomedical, Inc, Irvine, CA, USA) Infusion Set Failure Modes Infusion Set Failure Criteria Key Innovation and Benefit Provided N= 20 Subjects, N = 60 Infusion Sets Soft, Flexible Cannula Four Drug Delivery Ports Coil Reinforced Cannula Cannula Based Filter Angled Cannula Placement Only 77% of Teflon sets were functional after 3 days of use Source: Patel, J Diab Tech Therapeutics 2014 Technical Challenges and Key Issues Reasons for Device Removal 1. Uncorrectable hyperglycemia n Blood glucose >250mg/dl (14 mmol/L) n ≥2 hours after a meal n Not responsive to a pump bolus dose n Fall of ≥50mg/dl (3mmol/L) within 1 hour 2. Hyperglycemic episode with ketonemia n Blood glucose >250mg/dl or 14 mmol/L n Blood ketone ≥0.6 mmol/L n Not associated with acute intercurrent illness 3. Signs of infection n Erythema or induration >1cm in diameter 4. Non-resolvable insulin pump occlusion alarm n 88% of infusion sets lasted for 7-day wear period n Infusion site adverse events were minimal (data not shown) n No kinked cannulas were observed post-removal n No pump occlusion alarms were recorded n Follow-on studies underway with the SteadiSet™ system, consisting of the SteadiFlow cannula deployed using an auto-inserter Infusion sets have been called the Achilles heal of Insulin pump therapy. Their reliability can be quite poor, with 15–25% failing before 3 days of use in clinical studies. Infusion sets fail for many reasons as identified by the groundbreaking study of extended wear conducted by the team from Stanford University. There are a surprising number of technical challenges that must be faced to improve set reliability and extend infusion wear time. These include mechanical, biological, chemical, physiological and usability challenges. In this study, the 7-day survival rates of the investigational set were 95% for period one when saline was delivered and 88% for periods two and three combined. No serious adverse events were reported. Mild infusion site reactions occurred in 7 participants. Hyperglycemia was reported as an adverse event in 7 participants, resulting in 4 set removals. Signs of infusion site infection resulted in the 5th premature removal. Insulin use by standard 24 hour period. Partial data from day of insertion (1st calendar day) and day of removal (8th calendar day) are excluded. These study results confirm the feasibility of the extended-life investigational cannula. Larger, randomised studies are required to confirm these preliminary observations. We aimed to determine the feasibility of a prototype cannula for an extended wear infusion set. Twenty adults with type 1diabetes using IPT participated in a study with three study periods. For each period a new infusion set was inserted for an intended wear of 7 days. During Period 1 saline was infused via the investigational set through an additional insulin pump. During Periods 2 and 3 insulin lispro was delivered via the investigational set connected to the participant’s own insulin pump. Participants mean age was 44 years with a mean HbA1c of 7.3%. 50% were female. Three pumps were used: Medtronic 640G [n=11]; 670G [n=3];Tandem t-slim X2 [n=6]. The soft cannula material of the set is much more flexible than the Teflon material used in traditional infusion sets. This material results in a cannula that moves with the tissue for increased comfort and reduced inflammation. There are 3 additional side ports designed to deliver insulin over a wider area and prevent occlusions.The cannula is reinforced with a coil that prevents kinking, a common cause of infusion set failures. The coil also acts as a particulate filter, reducing particulates delivered by roughly 50%. Finally, the coil is placed in the tissue at an angle which is intended to further increase comfort and reduce inflammation. Research sponsored by Capillary Biomedical, Inc. and supported by JDRF award 2-IND-2016-232-M-X Catheter Failure 45% Pain at Infusion Site 20% Accidentally Pulled Out 20% Adhesive Failure 9% Infection 6% Mechanical Biological Chemical Psychological Inflammation Pain / irritation Infection Cannula kinking Occlusions Adhesion loss Preservative loss Particulate prevention Intimidation Apprehension Frustration Usability Time /effort Errors Waste Screening Treatment Period 3 (1 Week) CGM (Dexcom G5) and SMBG (Ascencia Contour) Clinic Visits Day 0 Insert Set #1 Remove Set #1 Insert Set #2 +7 (or earlier) (Day 7a = Day 0b) +7 (or earlier) (Day 7b = Day 0c) +7 (or earlier) (Day 7c) Remove Set #2 Insert Set #3 Remove Set #3 EOS Day -21 to 0 0 Treatment Period 2 (1 Week) Treatment Period 1 (1 Week) Pump (saline) + SteadiFlow infusion set Pump (insulin lispro) + SteadiFlow infusion set Pump (insulin lispro) + SteadiFlow infusion set Participant Diary Increases comfort Reduces inflammation Distributes insulin over a wide area Reduces occlusion risk Prevents kinking Reduces inflammation Increases comfort Reduces inflammation 0 10 20 30 40 50 60 70 80 90 100 0 1 2 3 4 5 6 7 Survival Percentage (%) Wear Time (Days) Kaplan-Meier Survival Plot of Primary Endpoint: Infusion Set Failure When Delivering Insulin (N=41 Devices, 20 Participants) Uncorrectable Hyperglycemia, N=3 Ketonemia after Insertion, N=1 Infection Leads to Removal, N=1 7 Day Duration, N=36 Prespecified protocol criteria for infusion set failure were not met 0 10 20 30 40 50 60 70 80 90 100 2 3 4 5 6 7 Insulin (U) Mean ± SD Day of Wear Total Insulin (U) by Day Feasibility of an Investigational Extended Wear Infusion Set for Insulin Pump Therapy (IPT) in People with Type 1 Diabetes Mellitus David N. O’Neal 1, 2 , Nisha Venkatesh 1,2, Katie Brown 1 , Elif Ekinci 1,3 , Spiros Fourlanos 1,4 , Jasmin Kastner 5 , Richard J. MacIsaac 1,2 , Douglas B. Muchmore 5 1. Department of Medicine, University of Melbourne, Melbourne,VIC, Australia 2. Department of Endocrinology and Diabetes, St Vincent’s Hospital Melbourne, Fitzroy,VIC, Australia 3. Department of Endocrinology and Diabetes, Austin Health, Heidelberg,VIC, Australia 4. Department of Endocrinology and Diabetes, The Royal Melbourne Hospital, Parkville,VIC, Australia 5. Capillary Biomedical Incorporated, Irvine, California, U.S.A.
Transcript of Feasibility of an Investigational Extended Wear Infusion ...
INTRODUCTION RESULTS
OBJECTIVE
MATERIALS
CONCLUSION
Insulin Pump Therapy (IPT) is limited by 3-day maximum cannula life and reported failure rates of 15-25%
SteadiFlow™ Technology: Kinkproof, Flexible Cannula with Sideports
88% IIS (36/41) Inserted In 20 Participants Successfully Delivered Insulin For 7-Days
Protocol-specified failure criteria were not well aligned with the routine practice of diabetes management
No significant difference in total insulin delivered by day was observed, although a subset of participants did increase use
SteadiFlow cannula is safe and well tolerated
Evaluate the feasibility and device performance of a prototype cannula for an extended wear infusion set
Infusion set with SteadiFlow™ cannula technology (Capillary Biomedical, Inc, Irvine, CA, USA)
Infusion Set Failure Modes
Infusion Set Failure Criteria
Key Innovation and Benefit Provided
N= 20 Subjects, N = 60 Infusion Sets
Soft, Flexible Cannula
Four Drug Delivery Ports
Coil Reinforced Cannula
Cannula Based Filter
Angled Cannula Placement
Only 77% of Teflon sets were functional after 3 days of use
Source: Patel, J Diab Tech Therapeutics 2014
Technical Challenges and Key Issues
Reasons for Device Removal
1. Uncorrectable hyperglycemia n Blood glucose >250mg/dl (14 mmol/L) n ≥2 hours after a meal n Not responsive to a pump bolus dosen Fall of ≥50mg/dl (3mmol/L) within 1 hour
2. Hyperglycemic episode with ketonemian Blood glucose >250mg/dl or 14 mmol/Ln Blood ketone ≥0.6 mmol/Ln Not associated with acute intercurrent illness
3. Signs of infectionn Erythema or induration >1cm in diameter
4. Non-resolvable insulin pump occlusion alarm
n 88% of infusion sets lasted for 7-day wear period
n Infusion site adverse events were minimal (data not shown)
n No kinked cannulas were observed post-removal
n No pump occlusion alarms were recorded
n Follow-on studies underway with the SteadiSet™ system, consisting of the SteadiFlow cannula deployed using an auto-inserter
Infusion sets have been called the Achilles heal of Insulin pump therapy. Their reliability can be quite poor, with 15–25% failing before 3 days of use in clinical studies. Infusion sets fail for many reasons as identified by the groundbreaking study of extended wear conducted by the team from Stanford University. There are a surprising number of technical challenges that must be faced to improve set reliability and extend infusion wear time. These include mechanical, biological, chemical, physiological and usability challenges.
In this study, the 7-day survival rates of the investigational set were 95% for period one when saline was delivered and 88% for periods two and three combined. No serious adverse events were reported. Mild infusion site reactions occurred in 7 participants. Hyperglycemia was reported as an adverse event in 7 participants, resulting in 4 set removals. Signs of infusion site infection resulted in the 5th premature removal.
Insulin use by standard 24 hour period. Partial data from day of insertion (1st calendar day) and day of removal (8th calendar day) are excluded.
These study results confirm the feasibility of the extended-life investigational cannula. Larger, randomised studies are required to confirm these preliminary observations.
We aimed to determine the feasibility of a prototype cannula for an extended wear infusion set. Twenty adults with type1diabetes using IPT participated in a study with three study periods. For each period a new infusion set was inserted for an intended wear of 7 days. During Period1 saline was infused via the investigational set through an additional insulin pump. During Periods 2 and 3 insulin lispro was delivered via the investigational set connected to the participant’s own insulin pump. Participants mean age was 44 years with a mean HbA1c of 7.3%. 50% were female. Three pumps were used: Medtronic 640G [n=11]; 670G [n=3]; Tandem t-slim X2 [n=6].
The soft cannula material of the set is much more flexible than the Teflon material used in traditional infusion sets. This material results in a cannula that moves with the tissue for increased comfort and reduced inflammation. There are 3 additional side ports designed to deliver insulin over a wider area and prevent occlusions. The cannula is reinforced with a coil that prevents kinking, a common cause of infusion set failures. The coil also acts as a particulate filter, reducing particulates delivered by roughly 50%. Finally, the coil is placed in the tissue at an angle which is intended to further increase comfort and reduce inflammation.
Research sponsored by Capillary Biomedical, Inc. and supported by JDRF award 2-IND-2016-232-M-X
Catheter Failure45%
Pain at Infusion Site20%
AccidentallyPulled Out
20%
AdhesiveFailure
9%
Infection6% Mechanical
Biological
Chemical
Psychological
InflammationPain / irritationInfection
Cannula kinkingOcclusionsAdhesion loss
Preservative lossParticulate prevention
IntimidationApprehensionFrustration
UsabilityTime /effortErrorsWaste
N= 20 Subjects, N = 60 Infusion Sets
Screening
Treatment Period 3 (1 Week)
CGM (Dexcom G5) and SMBG (Ascencia Contour)
Clinic Visits
Day 0Insert Set #1
Remove Set #1Insert Set #2
+7 (or earlier)(Day 7a = Day 0b)
+7 (or earlier)(Day 7b = Day 0c)
+7 (or earlier)(Day 7c)
Remove Set #2Insert Set #3
Remove Set #3EOS
Day -21 to 0 0
Treatment Period 2 (1 Week)Treatment Period 1 (1 Week)
Pump (saline) +SteadiFlow infusion set
Pump (insulin lispro) +SteadiFlow infusion set
Pump (insulin lispro) +SteadiFlow infusion set
Pump & CGMData Download
Participant Diary
Increases comfortReduces inflammation
Distributes insulin over a wide area Reduces occlusion risk
Prevents kinking
Reduces inflammation
Increases comfortReduces inflammation
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7
Surv
ival
Per
cent
age
(%)
Wear Time (Days)
Kaplan-Meier Survival Plot of Primary Endpoint: Infusion Set Failure When Delivering Insulin (N=41 Devices, 20 Participants)
UncorrectableHyperglycemia,
N=3 Ketonemia afterInsertion, N=1
Infection Leadsto Removal, N=1
7 Day Duration, N=36
Prespecified protocol criteria for infusion set failure were not met
0
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70
80
90
100
2 3 4 5 6 7
Insu
lin (
U)
Mea
n ±
SD
Day of Wear
Total Insulin (U) by Day
Feasibility of an Investigational Extended Wear Infusion Set for Insulin Pump Therapy (IPT) in People with Type 1 Diabetes Mellitus
David N. O’Neal1, 2, Nisha Venkatesh1,2, Katie Brown1, Elif Ekinci1,3, Spiros Fourlanos1,4, Jasmin Kastner5, Richard J. MacIsaac1,2, Douglas B. Muchmore5
1. Department of Medicine, University of Melbourne, Melbourne, VIC, Australia 2. Department of Endocrinology and Diabetes, St Vincent’s Hospital Melbourne, Fitzroy, VIC, Australia
3. Department of Endocrinology and Diabetes, Austin Health, Heidelberg, VIC, Australia4. Department of Endocrinology and Diabetes, The Royal Melbourne Hospital, Parkville, VIC, Australia
5. Capillary Biomedical Incorporated, Irvine, California, U.S.A.
