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Replication of the CANVAS Diabetes Trial in Healthcare Claims

Completed
Conditions
Diabetes
Interventions
Drug: DPP-4 inhibitor
Registration Number
NCT03936010
Lead Sponsor
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
152202
Inclusion Criteria
  • Man or woman with a diagnosis of type 2 diabetes with glycated hemoglobin level ≥7.0% to≤10.5% at screening and be either

    1. not currently on antihyperglycemic agent (AHA) therapy or
    2. on AHA monotherapy or combination therapy with any approved class of agents: e.g., sulfonylurea, metformin, peroxisome proliferator-activated receptor gamma (PPARγ) agonist, alpha-glucosidase inhibitor, glucagon-like peptide-1 (GLP-1) analogue, dipeptidyl peptidase-4 (DPP-4) inhibitor, or insulin.
  • Age ≥30 years with documented symptomatic atherosclerotic cardiovascular disease

  • Age ≥50 years with 2 or more of the following risk factors determined at the screening visit

Exclusion Criteria
  • History of diabetic ketoacidosis, type 1 diabetes, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy.
  • History of one or more severe hypoglycemic episode within 6 months before screening
  • Ongoing, inadequately controlled thyroid disorder.
  • Renal disease that required treatment with immunosuppressive therapy or a history of dialysis or renal transplant.
  • MI, unstable angina, revascularization procedure, or cerebrovascular accident within 3 months before screening, or a planned revascularization procedure, or history of New York Heart Association (NYHA) Class IV cardiac disease.
  • Findings on 12-lead electrocardiogram (ECG) that would require urgent diagnostic evaluation or intervention
  • History of hepatitis B surface antigen or hepatitis C antibody positive
  • Any history of or planned bariatric surgery.
  • History of malignancy within 5 years before screening
  • History of human immunodeficiency virus (HIV) antibody positive.
  • Subject has a current clinically important hematological disorder (e.g., symptomatic anemia, proliferative bone marrow disorder, thrombocytopenia).
  • Major surgery (i.e., requiring general anesthesia) within 3 months of the screening visit or any surgery planned during the subject's expected participation in the study
  • Current use of other sodium glucose co-transporter 2 (SGLT2) inhibitor.
  • Current use of a corticosteroid medication or immunosuppressive agent, or likely to require treatment with a corticosteroid medication

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
DPP4iDPP-4 inhibitorReference group
CanagliflozinCanagliflozinExposure group
Primary Outcome Measures
NameTimeMethod
Relative hazard of composite outcome of Stroke, MI, and MortalityThrough study completion (a median of 120-140 days)

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

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Brigham & Women's Hospital

🇺🇸

Boston, Massachusetts, United States

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