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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 06/15/2021.
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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 06/15/2021.

Replication of the CANVAS Diabetes Trial in Healthcare Claims

Clinicaltrials.gov identifier NCT03936010

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: Canagliflozin
    Drug: DPP-4 inhibitor
  • 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: 152202 participants
  • Observational Model: Cohort
  • Time Perspective: Retrospective
  • Official Title: Replication of Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes (CANVAS Trial)
  • 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
: Canagliflozin
Exposure group
Drug: Canagliflozin
Canagliflozin dispensing claim is exposure
: DPP4i
Reference group
Drug: DPP-4 inhibitor
DPP4 inhibitor dispensing claim is 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 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.
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
  • Sampling Method: Non-Probability Sample
  • Study Population: This study will involve a new user, parallel group, cohort study design comparing canagliflozin to the DPP-4 inhibitor (DPP4i) antidiabetic class. DPP4is serve as a proxy for placebo, since this class of antidiabetic drugs is not known to have an impact on the outcome of interest. The comparison against DPP4 inhibitors is the primary comparison. Initiators of 2nd generation sulfonylureas are used as a secondary comparator group. The patients will be required to have continuous enrollment during the baseline period of 180 days before initiation of canagliflozin 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.

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

Eligible cohort entry dates: 4/1/2013-12/31/2016 (market availability of sitagliptin in the
U.S. started on 10/17/2006). For Optum, 4/1/2013-9/30/2017.

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

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

Contacts and Locations

United States, Massachusetts
Brigham & Women's Hospital

Sponsors and Collaborators

Brigham and Women's Hospital


Principal Investigator: Jessica Franklin, PhD Brigham and Womens

More Information
  • Responsible Party: Brigham and Women's Hospital
  • ClinicalTrials.gov Identifier: NCT03936010 History of Changes
  • Other Study ID Numbers: DUPLICATE-CANVAS
  • 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
  • Product Manufactured in and Exported from the U.S.: Yes
  • Additional relevant MeSH terms: Diabetes Mellitus