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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P160017 / PAS001 |
| Date Original Protocol Accepted |
12/22/2016
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| Date Current Protocol Accepted |
04/19/2021
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| Study Name |
MiniMed 670G Post Approval Study
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| Device Name |
MiniMed 670G System
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| Clinical Trial Number(s) |
NCT02130284 NCT02246582 NCT02463097
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| General Study Protocol Parameters |
| Study Design |
Randomized Clinical Trial
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| Data Source |
New Data Collection
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| Comparison Group |
Concurrent & Historical Control
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| Analysis Type |
Descriptive
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| Study Population |
Child: 2-12 yrs,
Adolescent: 13-18 yrs,
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
This is a multi-center, randomized, parallel, adaptive controlled trial in adult and pediatric patients with Type 1 Diabetes using Hybrid Closed Loop System (HCL) and/or control (CSII, MDI, or SAP) in the home setting. Three cohorts, each consisting of a control arm (CSII, MDI, or SAP) and an HCL arm and further divided by A1C group (A1C > 8% or A1C < 8%), will participate in the 6-month study period followed by a 6-month continuation period where all subjects will use HCL. The purpose of this study is to demonstrate the safety and effectiveness of the HCL in the study population.
This study includes the continued follow-up of premarket cohorts and new subject enrollment.
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| Study Population |
Adult and pediatric patients (2-80 years of age) with type 1 diabetes that meet the inclusion/exclusion criteria will be studied.
The device is investigational in ages 2-13 years. The 2-13 year age group will also be studied under an approved IDE.
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| Sample Size |
A minimum of 1120 subjects will be enrolled
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| Key Study Endpoints |
Primary Safety Endpoint
The primary safety endpoint is the event rate of severe hypoglycemia and DKA from both A1C Groups (baseline A1C > 8% and baseline A1C < 8%) during the first 6 months of study phase and second 6 months of continuation phase. The descriptive summary statistics will be presented by number of event and event rate (100 patient years) for severe hypoglycemia and DKA separately.
The safety of the study will be evaluated and summarized per arm, including but not limited to the following:
• Diabetic ketoacidosis (DKA)
• Severe hypoglycemia
• Severe hyperglycemia
• Serious adverse events (SAEs)
• Unanticipated adverse device effects (UADEs)
Descriptive analyses will be performed to assess the primary safety endpoint. Event rates of severe hypoglycemia and DKA will be compared to: (1) the target event rate (defined by the medical literature and other studies) and (2) the control groups (CSII, MDI, SAP).
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| Follow-up Visits and Length of Follow-up |
Follow-up visits are scheduled throughout the study period up to 6 months and throughout the continuation period up to 6 months.
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
817
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| Actual Number of Sites Enrolled |
34
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| Patient Follow-up Rate |
A total of 817 subjects ages 14 years and older were enrolled across all three treatment cohorts of the study. The Sponsor had an overall
enrollment goal of 1,120 subjects for all age groups (participants 2 years and older). Results are summarized by treatment cohort below.
Cohort 1 (Hybrid Closed Loop (HCL) vs. Continuous Subcutaneous Insulin Infusion (CSII)): A total of 289 subjects were enrolled in the
study. A total of 270 subjects entered the Study Period. A total of 251 subjects completed the Study Period. The follow-up rate was 93.0%
(251/270).
Cohort 2 (HCL vs Multiple Daily Injection (MDI)): A total of 237 subjects were enrolled in the study. A total of 209 subjects entered the
Study period. A total of 189 subjects completed the Study period. The follow-up rate was 90.4% (189/209).
Cohort 3 (HCL vs Sensor Augmented Pump (SAP)): A total of 291 subjects were enrolled in the study. A total of 263 subjects entered the
Study period. A total of 242 subjects completed the Study period. The follow-up rate was 92.0% (242/263).
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| Final Safety Findings |
Cohort 1: Of the 450 adverse events reported through the end of the Study Period, 11% (N=50) were classified as device related, including
glycemic events (e.g., severe hyperglycemia, hypoglycemia), skin issues (e.g., abscess, dermatitis, skin infection at the infusion set site
and skin irritation), and bleeding at the sensor insertion site. There was one report of DKA, 6 reports of severe hypoglycemia, and 50 reports
of severe hyperglycemia.
Cohort 2: Of the 316 adverse events reported through the end of the Study period, 16% (N=52) were classified as device related, including
glycemic events (e.g., hyperglycemia, severe hyperglycemia, hypoglycemia), skin issues (e.g., dermatitis, skin infection at the
infusion set site and skin irritation), and bleeding at the sensor insertion site. There was one report of DKA, 6 reports of severe
hypoglycemia, and 19 reports of severe hyperglycemia.
Cohort 3: Of the 470 adverse events reported through the end of the Study period, 16% (N=76) were classified as device related, including
glycemic events (e.g., hyperglycemia, severe hyperglycemia, hypoglycemia) and skin issues (e.g., dermatitis and/or skin irritation at
the sensor site, skin infection at the infusion set site). There were no reports of DKA, 11 reports of severe hypoglycemia, and 44 reports of
severe hyperglycemia. There were no reports of serious unanticipated adverse device effects or deaths in any cohort.
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| Final Effect Findings |
The co-primary effectiveness endpoints for all three cohorts were
stratified into two groups: Group 1 for subjects with a baseline A1C >
8%, and Group 2 for subjects with a baseline A1C = 8%.
Cohort 1:
Group 1 (baseline A1C > 8%): change in A1C:
From baseline to end of study, the mean change in A1C was -
1.7±1.3% (95% Confidence Interval (CI): -2.0, -1.3) for the HCL Arm
(N=64) and -0.9±0.8% (95% CI: -1.1, -0.7) for the Control Arm
(N=64). The estimated mean difference (HCL vs CSII) was -0.8±1.1%
(95% CI: -1.2, -0.4).
Group 2 (baseline A1C = 8%): time in CGM < 70 mg/dL range:
From baseline to end of study, the mean change in time in
hypoglycemic range was 2.3±1.9% (95% Confidence Interval (CI):
1.8, 2.8) for the HCL Arm (N=62) and 7.6±5.3% (95% CI: 6.2, 8.9)
for the Control Arm (N=60). The estimated mean difference (HCL vs
CSII) was -5.2±4.0% (95% CI: -6.6, -3.8).
Cohort 2:
Group 1 (baseline A1C > 8%): change in A1C:
From baseline to end of study, the mean change in A1C was -
1.5±1.0% (95% Confidence Interval (CI): -1.8, -1.2) for the HCL Arm
(N=39) and -0.7±1.0% (95% CI: -1.0, -0.4) for the Control Arm
(N=36). The estimated mean difference (HCL vs MDI) was -0.8±1.0%
(95% CI: -1.3, -0.3).
Group 2 (baseline A1C = 8%): time in CGM < 70 mg/dL range:
From baseline to end of study, the mean change in time in
hypoglycemic range was 2.8±2.8% (95% Confidence Interval (95%
CI): 2.0, 3.5) for the HCL Arm (N=53) and 7.1±5.3% (95% CI: 5.6,
8.6) for the Control Arm (N=51). The estimated mean difference
(HCL vs MDI) was -4.3±4.2% (95% CI: -6.0,-2.7).
Cohort 3:
Group 1 (baseline A1C > 8%): change in A1C:
From baseline to end of study, the mean change in A1C was -
0.7±0.7% (95% Confidence Interval (CI): -1.0, -0.5) for the HCL Arm
(N=39) and -0.8±0.9% (95% CI: -1.1, -0.5) for the Control Arm
(N=44). The estimated mean difference (HCL vs SAP) was 0.1±0.8%
(95% CI: -0.3,0.4).
Group 2 (baseline A1C = 8%): time in CGM < 70 mg/dL range:
From baseline to end of study, the mean change in time in
hypoglycemic range was 2.3±2.3% (95% Confidence Interval (CI):
1.8, 2.8) for the HCL Arm (N=77) and 3.4±3.0% (95% CI: 2.7, 4.1)
for the Control Arm (N=76). The estimated mean difference (HCL vs
SAP) was -1.1±2.7% (95% CI: -2.0, -0.3).
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| Study Strengths & Weaknesses |
Strengths: This post-approval study included users aged 14-80 across
34 sites transitioning to the MiniMed 670G/770G Hybrid Closed Loop
system from three different baseline therapy options (MDI, CSII and
SAP) which were representative of the standard of care for people
with Type 1 Diabetes in the United States at the time of study
initiation. The incident rates of safety events (severe hypoglycemia
and diabetic ketoacidosis) of users on the MiniMed 670G/770G were
below the prespecified threshold for all cohorts. The post-approval
study confirms that the MiniMed 670G/770G System is safe when
used as intended.
Weaknesses: The post-approval study included mostly white device
users. There is uncertainty remaining regarding the risk/benefit profile
of the device when used in the broader intended use population.
However, available data from this post-approval study and additional
data from the post-market surveillance program support safety of the
MiniMed 670G/770G System when used as intended in these age
groups.
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| Recommendations for Labeling Changes |
Results of the post-approval study does not change the benefits and
risks conclusions of the original PMA approval. Labeling changes are
recommended to include PAS results.
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