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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/22/2021.

Replication of the SAVOR-TIMI Diabetes Trial in Healthcare Claims

Clinicaltrials.gov identifier NCT03936023

Recruitment Status Active, not recruiting

First Posted May 3, 2019

Last update posted January 2, 2020

Study Description

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.

  • Condition or Disease:Diabetes
  • Intervention/Treatment: Drug: Saxagliptin
    Drug: Sulfonylurea
  • Phase: N/A
Detailed Description

This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.

Study Design
  • Study Type: Observational
  • Actual Enrollment: 182126 participants
  • Observational Model: Cohort
  • Time Perspective: Retrospective
  • Official Title: Replication of the SAVOR-TIMI Diabetes Trial in Healthcare Claims
  • Actual Study Start Date: September 2017
  • Estimated Primary Completion Date: September 2020
  • Estimated Study Completion Date: September 2020
Groups and Cohorts
Groups/Cohorts Intervention/treatment
: Saxagliptin
Exposure Group
Drug: Saxagliptin
Saxagliptin dispensing claim is the exposure
: 2nd Generation SUs
Reference Group
Drug: Sulfonylurea
2nd generation sulfonylurea dispensing claim is used as the reference
Outcome Measures
  • Primary Outcome Measures: 1. Relative hazard of composite outcome of Stroke, MI, and Mortality [ Time Frame: Through study completion (a median of 134-151 days) ]
    Relative hazard of composite outcome of MI, stroke, and mortality - Please refer to uploaded protocol for full definition due to size limitations.
Eligibility Criteria
  • Ages Eligible for Study: 40 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: Yes
  • 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.
Criteria

Please see: https://drive.google.com/drive/folders/1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV for
full code and algorithm definitions.

Eligible cohort entry dates:

Market availability of saxagliptin in the U.S. started on July 31, 2009 For Marketscan and
Medicare: July 31, 2009-Dec 31, 2016 (end of data availability).

For Optum: July 31, 2009-Sep 30, 2017 (end of data availability).

Inclusion Criteria:

- 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

Exclusion Criteria:

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 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 (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

Contacts and Locations
Contacts
Locations

United States, Massachusetts
Brigham & Women's Hospital
Boston

Sponsors and Collaborators

Brigham and Women's Hospital

Investigators

Principal Investigator: Jessica Franklin, PhD Brigham and Womens

More Information
  • Responsible Party: Brigham and Women's Hospital
  • ClinicalTrials.gov Identifier: NCT03936023 History of Changes
  • Other Study ID Numbers: DUPLICATE-SAVOR-TIMI
  • First Posted: May 3, 2019 Key Record Dates
  • Last Update Posted: January 2, 2020
  • Last Verified: December 2019
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Additional relevant MeSH terms: Diabetes Mellitus