Replication of the CANVAS Diabetes Trial in Healthcare Claims

NCT03936010 | Completed FDA Drug

• 1 other identifier: 2018P002966-DUP-CANVAS
• Study Type: observational
• Target: 152,202
• 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 120-140 days)

Study Arms (2)

DPP4i

Reference group

Drug: DPP-4 inhibitor

Canagliflozin

Exposure group

Drug: Canagliflozin

Interventions

Canagliflozin DRUG

Canagliflozin dispensing claim is exposure

Canagliflozin

DPP-4 inhibitor DRUG

DPP4 inhibitor dispensing claim is reference

DPP4i

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• 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 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.

You may qualify if:

• Man or woman with a diagnosis of type 2 diabetes with glycated hemoglobin level ≥7.0% to≤10.5% at screening and be either
• not currently on antihyperglycemic agent (AHA) therapy or
• 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

You may not qualify if:

• 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

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

Canagliflozin; Dipeptidyl-Peptidase IV Inhibitors

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs

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: July 27, 2023

Record last verified: 2023-07

Locations

US (1)