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Replication of the SAVOR-TIMI Diabetes Trial in Healthcare Claims

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03936023
Recruitment Status : Active, not recruiting
First Posted : May 3, 2019
Last Update Posted : January 2, 2020
Sponsor:
Information provided by (Responsible Party):
Jessica Franklin, Brigham and Women's Hospital

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 Intervention/treatment
Diabetes Drug: Saxagliptin Drug: Sulfonylurea

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.

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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 22, 2017
Estimated Primary Completion Date : September 22, 2020
Estimated Study Completion Date : September 22, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Saxagliptin

Group/Cohort Intervention/treatment
2nd Generation SUs
Reference Group
Drug: Sulfonylurea
2nd generation sulfonylurea dispensing claim is used as the reference

Saxagliptin
Exposure Group
Drug: Saxagliptin
Saxagliptin dispensing claim is the exposure




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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 <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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03936023


Locations
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United States, Massachusetts
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02120
Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
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Principal Investigator: Jessica Franklin, PhD Brigham and Womens
  Study Documents (Full-Text)

Documents provided by Jessica Franklin, Brigham and Women's Hospital:
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Responsible Party: Jessica Franklin, Assistant Professor of Medicine, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT03936023    
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Saxagliptin
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents