Replication of the SAVOR-TIMI Diabetes Trial in Healthcare Claims

NCT03936023 | Completed FDA Drug

• 1 other identifier: 2018P002966-DUP-SAVOR-TIMI
• Study Type: observational
• Target: 182,126
• Locations: 1 country
• Sites: 1

Brief Summary

Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.

Conditions

Diabetes

Outcome Measures

Primary Outcomes (1)

• Relative hazard of composite outcome of Stroke, MI, and Mortality

  Relative hazard of composite outcome of MI, stroke, and mortality - Please refer to uploaded protocol for full definition due to size limitations.

  Through study completion (a median of 134-151 days)

Study Arms (2)

2nd Generation SUs

Reference Group

Drug: Sulfonylurea

Saxagliptin

Exposure Group

Drug: Saxagliptin

Interventions

Saxagliptin DRUG

Saxagliptin dispensing claim is the exposure

Saxagliptin

Sulfonylurea DRUG

2nd generation sulfonylurea dispensing claim is used as the reference

2nd Generation SUs

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study will involve a new user, parallel group, cohort study design comparing saxagliptin to the 2nd generation sulfonylurea (SU) antidiabetic class as a proxy for placebo. SUs are not known to have an impact on the outcome of interest. In addition, SUs were the most frequent background treatment in SAVOR-TIMI53 (after metformin), and DPP4i and SUs are preferentially prescribed to similarly older patients in real world (Patorno et al., 2019). The patients will be required to have continuous enrollment during the baseline period of 180 days before initiation of saxagliptin or a comparator drug (cohort entry date). Follow-up for the outcome (3P-MACE), begins the day after drug initiation. As in the trial, patients are allowed to take other antidiabetic medications during the study.

You may qualify if:

• Diagnosed with T2DM based on the current American Diabetes Association guidelines Age ≥40 years Glycated hemoglobin level of ≥6.5% (based on the last measured and documented laboratory measurement in the previous 6 months)
• High risk for a CV event defined as having either established CV disease and/or multiple risk factors:
• History of established cardiovascular disease
• Ischemic heart disease, and/or
• Peripheral vascular disease (eg, intermittent claudication), and/or
• Ischemic stroke
• Multiple risk factors for vascular disease - At least 55 years of age (men) or 60 years of age (women), AND at least one of the following additional risk factors
• Dyslipidemia (based on the last measured and documented laboratory measurement in the previous 6 months and defined as at least 1 of the following):
• High level of low-density lipoprotein cholesterol (LDL-C), defined as N130 mg/dL (N 3.36 mmol/L) regardless of lipid-lowering therapy
• Low level of high-density lipoprotein cholesterol (HDL-C), defined as b40 mg/dL (b1.04 mmol/L) for men or b50 mg/dL (b1.30 mmol/L) for women
• Hypertension, as confirmed at the enrolment visit
• BP N140/N90 mm Hg, or
• BP N130/N80 mm Hg on BP-lowering agent
• Currently smoking, as confirmed at the enrolment visit Women of childbearing potential must take precautions to avoid pregnancy throughout the study and for 4 weeks after intake of the last dose. Men participating in the study should also take precautions not to father a childwhile participating in the study and for 4 weeks after intake of the last dose.
• Provision of informed consent before any study specific procedures

You may not qualify if:

• Current or previous (within 6 months) treatment with an incretin-based therapy such as DPP-4 inhibitors and/or GLP-1 mimetics Acute vascular (cardiac or stroke) event \<2 months before randomization Initiation of chronic dialysis and/or renal transplant and/or a serum creatinine \>6.0 mg/dL Pregnant or breastfeeding History of human immunodeficiency virus Patients being treated for severe autoimmune diseases such as lupus Any patient currently receiving long-term (\>30 consecutive days) treatment with an oral steroid Patients with
• Body mass index \>50 kg/m2
• Last measured HbA1c ≥12%
• Sustained BP \>180/100 mm Hg
• LDL-C \>250 mg/dL (\>6.48 mmol/L) (based on the last measured and documented laboratory measurement in the previous 6 months) regardless of lipid-lowering therapy
• Triglycerides \>1,000 mg/dL (N11.3 mmol/L) (based on the last measured and documented laboratory measurement in the previous 6months)
• HDL-C b25 mg/dL (\<0.64 mmol/L) (based on the last measured and documented laboratory measurement in the previous 6 months)
• Known liver function tests \>3 times upper limit of normal (ULN) (based on the last measured and documented laboratory measurement in the previous 6 months) Involvement in the planning and/or conduct of the study (applies to both AstraZeneca and Bristol-- Myers Squibb or representative staff and/or staff at the study site) Previous randomization in the present study Participation in another clinical study with an investigational product and/or intervention within 30 days before visit 1 Individuals at risk for poor protocol or medication compliance

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham & Women's Hospital

Boston, Massachusetts, 02120, United States

Location

Related Publications (1)

• Franklin JM, Patorno E, Desai RJ, Glynn RJ, Martin D, Quinto K, Pawar A, Bessette LG, Lee H, Garry EM, Gautam N, Schneeweiss S. Emulating Randomized Clinical Trials With Nonrandomized Real-World Evidence Studies: First Results From the RCT DUPLICATE Initiative. Circulation. 2021 Mar 9;143(10):1002-1013. doi: 10.1161/CIRCULATIONAHA.120.051718. Epub 2020 Dec 17.

  PMID: 33327727 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

saxagliptin; Sulfonylurea Compounds

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Study Officials

• Shirley Wang, PhD, ScM

  Brigham and Womens

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 29, 2019
• First Posted: May 3, 2019
• Study Start: September 22, 2017
• Primary Completion: February 18, 2021
• Study Completion: February 18, 2021
• Last Updated: August 1, 2023

Record last verified: 2023-07

Locations

US (1)