Study to Compare Efficacy of the MiniMed Paradigm REAL-Time System Vs. MDI in Subjects Naive to Insulin Pump Therapy (STAR3)

• ClinicalTrials.gov Identifier: NCT00417989
• Recruitment Status: Completed
• First Posted: January 4, 2007
• Results First Posted: March 10, 2011
• Last Update Posted: May 23, 2018
• Sponsor: Medtronic Diabetes
• Information provided by (Responsible Party): Medtronic Diabetes

Tracking Information

• First Submitted Date: January 2, 2007
• First Posted Date: January 4, 2007
• Results First Submitted Date: December 24, 2010
• Results First Posted Date: March 10, 2011
• Last Update Posted Date: May 23, 2018
• Study Start Date: January 2007
• Actual Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 9, 2011)

Change in A1c From Baseline to 52 Weeks [ Time Frame: Baseline and 52 weeks ]

Change is defined as A1c at Week 52 minus A1c at Baseline in each study arm. The difference between the change in each group will then be analyzed. A1c measure is defined as the percent of glycated hemoglobin using one standardized assay for all subjects.

• Original Primary Outcome Measures (submitted: January 2, 2007): Average decrease in A1c from baseline to end of Study Phase (52 weeks) for subjects in the "722 Group" is greater than that for subjects in the "Control (MDI) Group".

Current Secondary Outcome Measures (submitted: May 22, 2018)

• Difference in Frequency of Severe Hypoglycemia From Baseline to Week 52; [ Time Frame: Baseline and 52 weeks ]
  Severe Hypoglycemia is defined as a hypoglycemic episode absolutely requiring assistance from another person and preferably accompanied by a confirmatory Blood Glucose (BG) by finger stick of less than 50 mg/dL (2.8 mmol/L). The frequency evaluates the total number of events. This will be analyzed and compared between the two study arms from baseline to week 52.
• Overall Difference in Rate of Severe Hypoglycemia Events Between Study Arms From Baseline to Week 52 [ Time Frame: Baseline and 52 weeks ]
  Severe Hypoglycemia is defined as a hypoglycemic episode absolutely requiring assistance from another person and preferably accompanied by a confirmatory BG by finger stick of less than 50 mg/dL (2.8 mmol/L). The rate evaluates the number of participants that experienced at least one severe hypoglycemia event and compares this number between the two study arms from Baseline to week 52. This measure identifies the rate or frequency of unique participant events.
• Changes in Hypoglycemia Area Under the Curve (AUC) From Baseline to Week 52; [ Time Frame: Baseline and 52 weeks ]
  Hypoglycemia is defined as a recorded blood glucose event <70mg/dL. The amount of time spent below this parameter will be analyzed and compared between groups from Baseline to Week 52.
• Changes From Baseline in Hyperglycemia Area Under the Curve (AUC) From Baseline to Week 52 [ Time Frame: Baseline and 52 weeks ]
  Hyperglycemia is defined as a recorded blood glucose event > 180 mg/dL. The amount of time spent above this parameter will be analyzed and compared between groups from Baseline to Week 52.
• Quality of Life - Hypoglycemia Fear Scale (HFS), Overall Score [ Time Frame: Baseline and 52 weeks ]
  Difference of Baseline and 52 Weeks in Hypoglycemia Fear Scale (HFS) Overall Score between the two study arms (adult subjects only) is presented. Both baseline and 52 weeks scores range from 0-100, with lower scores suggest higher satisfaction. Therefore, a negative number in the difference suggests higher satisfaction at 52 Weeks than Baseline.
• Health Economic Outcome [ Time Frame: Baseline and 52 weeks ]
  Health Economic Outcome was a cost-effectiveness analysis combining estimates from the trial and the literature to populate the previously validated Center for Outcomes Research (CORE) Diabetes Model. Results represent the use of 3-day sensors. This analysis was restricted to only adult subjects (Age 19 to 70), therefore the number of participant analyzed is different. The goal was to estimate the long term cost effectiveness of Sensor Augmented Pump therapy from the perspective of the US health care system. The unit of measurement was cost in $ per year for sensor augmented pump group and MDI group. No formal statistical analysis was planned or performed
• Quality of Life - Short Form-36 (SF-36v2™), General Health [ Time Frame: Baseline and 52 Weeks ]
  Difference of Baseline and 52 Weeks in Short Form-36 (SF-36v2™), General Health, between the two study arms (adult subjects only) is presented. Both baseline and 52 weeks scores range from 0-100, with higher scores suggest higher satisfaction. Therefore, a positive number in the difference suggests higher satisfaction at 52 Weeks than Baseline.
• Quality of Life - Insulin Delivery System Rating Questionnaire (IDSRQ) for Subject Satisfaction With Type of Insulin Therapy [ Time Frame: Baseline and 52 Weeks ]
  Difference of Baseline and 52 Weeks in Insulin Delivery System Rating Questionnaire (IDSRQ) for Subject Satisfaction with Type of Insulin Therapy, between the two study arms is presented. Both baseline and 52 weeks scores range from 0-100, with higher scores suggest higher satisfaction. Therefore, a positive number in the difference suggests higher satisfaction at 52 Weeks than Baseline.

Original Secondary Outcome Measures (submitted: January 2, 2007)

• Incidence and frequency of severe hypoglycemia;
• Measure of glycemic variability (AUC);
• Quality of Life;
• Health Economic Outcomes (MRU)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Compare Efficacy of the MiniMed Paradigm REAL-Time System Vs. MDI in Subjects Naive to Insulin Pump Therapy
• Official Title: The STAR 3 Study - A Prospective, Randomized, Two-Arm Study to Compare the Efficacy of the MiniMed Paradigm REAL-Time System Versus Multiple Daily Injections (MDI) in Subjects Naïve to Insulin Pump Therapy

Brief Summary

Primary Outcomes: Average decrease in A1c from baseline to end of Study Phase (52 weeks) for subjects in the "722 Group" is greater than that for subjects in the "Control (MDI) Group".

Secondary Outcomes: Incidence and frequency of severe hypoglycemia; Measure of glycemic variability, Area Under the Curve (AUC); Quality of Life; and Health Economic Outcomes (MRU)

Detailed Description

Glycemic control remains a significant challenge for adult, adolescent and pediatric Type 1 diabetics. The current first line standard of care continues to be MDI therapy utilizing a long acting analog insulin. Continuous Glucose Monitoring (CGMS) is currently used by clinicians to record continuous, retrospective glucose measurements, which aid in identification of glycemic excursion patterns. This data is then used to make future therapy change recommendations. The MiniMed Paradigm REAL-Time System transmits real-time glucose measurements to the insulin pump every 5 minutes, allowing users to view their current glucose values, as well as to review glycemic excursions and trends over a 24-hour period. Additionally, data can be downloaded from the monitor to a personal computer, using appropriate software, so that the patient and physician can see a complete picture of glucose trends over time. The System will also alert users of high and low glucose levels, and allow subjects and their clinicians to treat to a therapeutic target HbA1c under carefully monitored conditions.

Subjects wearing the MiniMed Paradigm REAL-Time System will be compared to subjects that continue on their current MDI therapy, that includes a long acting analog insulin, over a 12 month period to evaluate changes in glycemic control (HbA1c).

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Type 1 Diabetes

Intervention

Device: MiniMed Paradigm REAL-Time System

Paradigm 722 insulin pump Paradigm REAL-Time Transmitter Sensor ComLink Paradigm Link glucose meter

Other Name: Medtronic Paradigm REAL-Time System

Study Arms

• Experimental: 722 sensor augmented pump
  722 arm: MiniMed Paradigm REAL-Time System using NovoLog/NovoRapid for 1 year
  Intervention: Device: MiniMed Paradigm REAL-Time System
• No Intervention: Multiple Daily Injections (MDI)
  MDI arm: Continue with current MDI therapy using Lantus and NovoLog/NovoRapid for 1 year

Publications *

• Perkins BA, Halpern EM, Orszag A, Weisman A, Houlden RL, Bergenstal RM, Joyce C. Sensor-augmented pump and multiple daily injection therapy in the United States and Canada: post-hoc analysis of a randomized controlled trial. Can J Diabetes. 2015 Feb;39(1):50-4. doi: 10.1016/j.jcjd.2014.03.003. Epub 2014 Aug 29.
• Bergenstal RM, Tamborlane WV, Ahmann A, Buse JB, Dailey G, Davis SN, Joyce C, Peoples T, Perkins BA, Welsh JB, Willi SM, Wood MA; STAR 3 Study Group. Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes. N Engl J Med. 2010 Jul 22;363(4):311-20. doi: 10.1056/NEJMoa1002853. Epub 2010 Jun 29. Erratum in: N Engl J Med. 2010 Sep 9;363(11):1092.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 9, 2011): 485
• Original Enrollment (submitted: January 2, 2007): 336
• Actual Study Completion Date: June 2010
• Actual Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Aged 7 to 70 years
• Has been treated by the Principal Investigator or referring physician within the same practice for at least six months prior to screening
• Is fluent in speaking, reading and understanding English
• Has Type 1 diabetes mellitus, diagnosed by c-peptide, insulin antibodies, or prior documented DKA, or by a clinical picture consistent with Type 1 diabetes and excluding type 2 diabetes i.e. - previous ketosis as evidenced by laboratory evidence of urine ketones or alteration in bicarbonate levels with corresponding increased glucose levels, diagnosed at least 6 months prior to study entry, or has a fasting C-peptide that meet criteria of 110% of lower limit of normal or 200% of lower limit of normal in the presence of renal insufficiency (creatinine clearance < 50ml/min) at screening
• Is insulin infusion pump naїve or has not used an insulin pump within the last three years
• Currently is treated with insulin administration by injection > (greater or equal to) three (3) times daily and therapy has included the use of a long acting analog insulin for at least the previous 3 months prior to screening
• Performs fingerstick blood glucose (BG) testing an average of four times per day in the 30 days prior to screening
• Within 6 months prior to study entry and at Screening Visit 1, subject has a documented A1c level =/> 7.4% and =/< 9.5%

Exclusion Criteria:

• Is pregnant or planning to become pregnant during the course of the study
• Has suffered two or more documented events of severe hypoglycemia without warning of impending low glucose levels, within the previous 12 months
• Currently using oral or injectable steroids or immunosuppressant medications
• Use of any other pharmaceutical agent, other than insulin to treat diabetes, within the three months prior to screening;
• Has a current history of alcohol or drug abuse
• Has a history of myocardial infarction, unstable angina, coronary artery bypass surgery, coronary artery stenting, transient ischemic attack (TIA), cerebrovascular accident (CVA), or thromboembolic disease in the 3 months prior to screening
• Has uncontrolled hypertension (diastolic blood pressure >100 mmHg and/or sustained systolic level [3 successive readings] > 160). Subjects who are taking antihypertensive medication will not be excluded provided they are maintained at a stable dose for 3 months prior to screening
• Has serious or unstable medical or psychological conditions (e.g., eating disorders, clinical depression, anxiety disorder) which, in the opinion of the Investigator, would compromise the subject's safety or successful participation in the study
• Is undergoing renal dialysis, including hemodialysis and continuous ambulatory peritoneal dialysis (CAPD)
• Has evidence of any allergic dermatological condition (e.g., severe adhesive sensitivity)
• Has recurrent episodes of skin infections or history of staphylococcus infection carrier state
• Has potential for lack of compliance or any other issue that may preclude the subject from satisfactory participation in the study, based on Investigatory judgment

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 7 Years to 70 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT00417989
• Other Study ID Numbers: CEP179/Z25
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Medtronic Diabetes
• Study Sponsor: Medtronic Diabetes
• Collaborators: Not Provided

Investigators

• Principal Investigator: Stephen N Davis, MD; University of Maryland, College Park
• Principal Investigator: William V Tamborlane, MD; Yale University
• Study Director: Scott W Lee, MD; Medtronic Minimed

• PRS Account: Medtronic Diabetes
• Verification Date: May 2018