DiabetesNCT03936010
Replication of the CANVAS Diabetes Trial in Healthcare Claims
An observational study of Diabetes, run by Brigham and Women's Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes
- What is being tested?
- Canagliflozin and DPP-4 inhibitor
- How many people
- 152,202 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Sep 2017to 18 Feb 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham & Women's Hospital
Boston, Massachusetts, 02120
About this study
Official title: Replication of Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes (CANVAS Trial)
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.
Read the 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
- Being tested
- Canagliflozin, DPP-4 inhibitor
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CanagliflozinDrug
Canagliflozin dispensing claim is exposure
DPP-4 inhibitorDrug
DPP4 inhibitor dispensing claim is reference
| Study group | Role | What they receive |
|---|---|---|
| DPP4i | Reference group Receives: Drug: DPP-4 inhibitor | |
| Canagliflozin | Exposure group Receives: Drug: Canagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Through study completion (a median of 120-140 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2019
- Study start22 Sep 2017
- Primary completion18 Feb 2021
- Study completion18 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DiabetesStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 152,202 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shirley Vichy Wang, Brigham and Women's Hospital
- Investigators
- Shirley Wang, PhD, ScM, Principal investigator, Brigham and Womens
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03936010
- Sponsor's protocol ID
- 2018P002966-DUP-CANVAS
- Status last verified
- Jul 2023
- First submitted
- 29 Apr 2019
- Last updated
- 27 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 33327727
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Replication of Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes (CANVAS Trial)
- ClinicalTrials.gov ID
- NCT03936010
- Acronym / sponsor ID
- 2018P002966-DUP-CANVAS
- Conditions
- Diabetes
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 152,202 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 22 Sep 2017 (actual)
- Primary completion
- 18 Feb 2021 (actual)
- Study completion
- 18 Feb 2021 (actual)
- First posted
- 3 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DPP4i | – | Drug: DPP-4 inhibitorReference group |
| Canagliflozin | – | Drug: CanagliflozinExposure group |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- Man or woman with a diagnosis of type 2 diabetes with glycated hemoglobin level ≥7.0% to≤10.5% at screening and be either
- 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
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CanagliflozinCanagliflozin dispensing claim is exposure | Drug | Canagliflozin |
| DPP-4 inhibitorDPP4 inhibitor dispensing claim is reference | Drug | DPP4i |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2023.
- Derived from this study: PubMed 33327727Franklin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shirley Wang, PhD, ScM principal investigator
Brigham and Womens
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetes, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relative hazard of composite outcome of Stroke, MI, and Mortality (time frame: Through study completion (a median of 120-140 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03936010, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2023.