Replication of the CANVAS Diabetes Trial in Healthcare Claims

NCT ID: NCT03936010

Last Updated: 2023-07-27

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 152202 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-09-22
• Study Completion Date: 2021-02-18

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.

Conditions

Diabetes

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

DPP4i

Reference group

DPP-4 inhibitor

Intervention Type: DRUG

DPP4 inhibitor dispensing claim is reference

Canagliflozin

Exposure group

Canagliflozin

Intervention Type: DRUG

Canagliflozin dispensing claim is exposure

Interventions

Canagliflozin

Canagliflozin dispensing claim is exposure

Intervention Type: DRUG

DPP-4 inhibitor

DPP4 inhibitor dispensing claim is reference

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Shirley Vichy Wang

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shirley Wang, PhD, ScM

Role: PRINCIPAL_INVESTIGATOR

Brigham and Womens

Locations

Brigham & Women's Hospital

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33327727 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2018P002966-DUP-CANVAS

Identifier Type: -

Identifier Source: org_study_id