A Study for Comparison of Canagliflozin Versus Alternative Antihyperglycemic Treatments on Risk of Heart Failure Hospitalization and Amputation for Participants With Type 2 Diabetes Mellitus and the Subpopulation With Established Cardiovascular Disease

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT03492580

Collaborator

(none)

714,582

Enrollment

Location

Actual Duration (Months)

176830

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary purpose of study is to estimate the incidence and comparative effect on health outcomes: 1) hospitalization for heart failure, 2) below knee lower extremity amputation. The date of first exposure to the particular drug(s) in the database, where the exposure start is between 1-April-2013 to 15-May-2017 and outcome data for these participants will be analyzed and reported in this study.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2 Cardiovascular Diseases	Drug: Canagliflozin Drug: Empagliflozin Drug: Dapagliflozin Drug: Dipeptidyl Peptidase-4 (DPP-4) Inhibitors Drug: Glucagon-like Peptide-1 (GLP-1) Agonist Drug: Anti-hyperglycemic Agents (AHA) Drug: Thiazolidinediones (TZD) Drug: Sulfonylureas (SU) Drug: Insulin

Study Design

Study Type:

Observational

Actual Enrollment :

714582 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

Official Title:

Comparison of Canagliflozin vs. Alternative Antihyperglycemic Treatments on Risk of Heart Failure Hospitalization and Amputation for Patients With Type 2 Diabetes Mellitus and the Subpopulation With Established Cardiovascular Disease

Actual Study Start Date :

Feb 22, 2018

Actual Primary Completion Date :

Apr 6, 2018

Actual Study Completion Date :

Jun 25, 2018

Arms and Interventions

Arm	Intervention/Treatment
Cohort 1: Canagliflozin A target cohort which includes new users of canagliflozin for clinical characterization, and population-level effect estimation. It will use 4 databases: 1. Truven Health MarketScan Commercial Claims and Encounters Database (CCAE) 2. Truven Health MarketScan Medicare Supplemental and Coordination of Benefits Database (MDCR) 3. Truven Health MarketScan Multi-state Medicaid Database (MDCD) 4. OptumInsight's de-identified Clinformatics Datamart, Extended-Date of Death (Optum).	Drug: Canagliflozin No intervention or treatment assignment imposed by this study. Participants received canagliflozin as a part of routine clinical practice.
Cohort 2: Canagliflozin with Cardiovascular Disease (CVD) A target cohort which includes new users of canagliflozin with established CVD for clinical characterization and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Canagliflozin No intervention or treatment assignment imposed by this study. Participants received canagliflozin as a part of routine clinical practice.
Cohort 3: Empagliflozin A comparator cohort which includes new users of empagliflozin for clinical characterization, and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Empagliflozin No intervention or treatment assignment imposed by this study. Participants received empagliflozin as a part of routine clinical practice.
Cohort 4: Empagliflozin with CVD A comparator cohort which includes new users of empagliflozin with established CVD for clinical characterization and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Empagliflozin No intervention or treatment assignment imposed by this study. Participants received empagliflozin as a part of routine clinical practice.
Cohort 5: Dapagliflozin A comparator cohort which includes new users of dapagliflozin for clinical characterization, and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Dapagliflozin No intervention or treatment assignment imposed by this study. Participants received dapagliflozin as a part of routine clinical practice.
Cohort 6: Dapagliflozin with CVD A comparator cohort which includes new users of dapagliflozin with established CVD for clinical characterization and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Dapagliflozin No intervention or treatment assignment imposed by this study. Participants received dapagliflozin as a part of routine clinical practice.
Cohort 7: Empagliflozin or Dapagliflozin A target cohort which includes new users of empagliflozin or dapagliflozin for clinical characterization, and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Empagliflozin No intervention or treatment assignment imposed by this study. Participants received empagliflozin as a part of routine clinical practice. Drug: Dapagliflozin No intervention or treatment assignment imposed by this study. Participants received dapagliflozin as a part of routine clinical practice.
Cohort 8: Empagliflozin or Dapagliflozin with CVD A target cohort which includes new users of empagliflozin or dapagliflozin with established CVD for clinical characterization, and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Empagliflozin No intervention or treatment assignment imposed by this study. Participants received empagliflozin as a part of routine clinical practice. Drug: Dapagliflozin No intervention or treatment assignment imposed by this study. Participants received dapagliflozin as a part of routine clinical practice.
Cohort 9: DPP-4 inhibitor (i)/ GLP-1 agonist (a)/ other AHA A comparator cohort which includes new users of any dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) agonist, or other select antihyperglycemic agents (AHA) for clinical characterization, and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Dipeptidyl Peptidase-4 (DPP-4) Inhibitors No intervention or treatment assignment imposed by this study. Participants received DPP-4 inhibitor as a part of routine clinical practice. DPP-4 inhibitors includes: alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin. Drug: Glucagon-like Peptide-1 (GLP-1) Agonist No intervention or treatment assignment imposed by this study. Participants received GLP-1 agonist as a part of routine clinical practice. GLP-1 agonists includes: albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide. Drug: Anti-hyperglycemic Agents (AHA) No intervention or treatment assignment imposed by this study. Participants received other selected AHA as a part of routine clinical practice. Other select AHAs includes: acarbose, bromocriptine, miglitol, nateglinide, repaglinide.
Cohort 10: DPP-4 (i)/ GLP-1 (a)/ other AHA with CVD A comparator cohort which includes new users of any DPP-4 inhibitor, GLP-1 agonist, or other select AHA with established CVD for clinical characterization, and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Dipeptidyl Peptidase-4 (DPP-4) Inhibitors No intervention or treatment assignment imposed by this study. Participants received DPP-4 inhibitor as a part of routine clinical practice. DPP-4 inhibitors includes: alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin. Drug: Glucagon-like Peptide-1 (GLP-1) Agonist No intervention or treatment assignment imposed by this study. Participants received GLP-1 agonist as a part of routine clinical practice. GLP-1 agonists includes: albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide. Drug: Anti-hyperglycemic Agents (AHA) No intervention or treatment assignment imposed by this study. Participants received other selected AHA as a part of routine clinical practice. Other select AHAs includes: acarbose, bromocriptine, miglitol, nateglinide, repaglinide.
Cohort 11: DPP-4 (i),GLP-1 (a),TZD, SU, insulin, other AHA A comparator cohort which includes new users of any DPP-4 inhibitor, GLP-1 agonist, thiazolidinediones (TZD), sulfonylureas (SU), insulin, or other select AHA for clinical characterization, and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Dipeptidyl Peptidase-4 (DPP-4) Inhibitors No intervention or treatment assignment imposed by this study. Participants received DPP-4 inhibitor as a part of routine clinical practice. DPP-4 inhibitors includes: alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin. Drug: Glucagon-like Peptide-1 (GLP-1) Agonist No intervention or treatment assignment imposed by this study. Participants received GLP-1 agonist as a part of routine clinical practice. GLP-1 agonists includes: albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide. Drug: Anti-hyperglycemic Agents (AHA) No intervention or treatment assignment imposed by this study. Participants received other selected AHA as a part of routine clinical practice. Other select AHAs includes: acarbose, bromocriptine, miglitol, nateglinide, repaglinide. Drug: Thiazolidinediones (TZD) No intervention or treatment assignment imposed by this study. Participants received TZD as a part of routine clinical practice. TZDs includes: pioglitazone, rosiglitazone, troglitazone. Drug: Sulfonylureas (SU) No intervention or treatment assignment imposed by this study. Participants received SU as a part of routine clinical practice. SUs includes: glipizide, glyburide, glimepiride, chlorpropamide, tolazamide, tolbutamide, acetohexamide Drug: Insulin No intervention or treatment assignment imposed by this study. Participants received Insulin as a part of routine clinical practice.
Cohort 12: DPP-4(i), GLP-1(a), TZD, SU, insulin, AHA with CVD A comparator cohort which includes new users of any DPP-4 inhibitor, GLP-1 agonist, TZD, SU, insulin, or other select AHA with established CVD for clinical characterization, and population-level effect estimation. It will use 4 databases: 1. CCAE 2. MDCR 3. MDCD 4. Optum.	Drug: Dipeptidyl Peptidase-4 (DPP-4) Inhibitors No intervention or treatment assignment imposed by this study. Participants received DPP-4 inhibitor as a part of routine clinical practice. DPP-4 inhibitors includes: alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin. Drug: Glucagon-like Peptide-1 (GLP-1) Agonist No intervention or treatment assignment imposed by this study. Participants received GLP-1 agonist as a part of routine clinical practice. GLP-1 agonists includes: albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide. Drug: Anti-hyperglycemic Agents (AHA) No intervention or treatment assignment imposed by this study. Participants received other selected AHA as a part of routine clinical practice. Other select AHAs includes: acarbose, bromocriptine, miglitol, nateglinide, repaglinide. Drug: Thiazolidinediones (TZD) No intervention or treatment assignment imposed by this study. Participants received TZD as a part of routine clinical practice. TZDs includes: pioglitazone, rosiglitazone, troglitazone. Drug: Sulfonylureas (SU) No intervention or treatment assignment imposed by this study. Participants received SU as a part of routine clinical practice. SUs includes: glipizide, glyburide, glimepiride, chlorpropamide, tolazamide, tolbutamide, acetohexamide Drug: Insulin No intervention or treatment assignment imposed by this study. Participants received Insulin as a part of routine clinical practice.

Outcome Measures

Primary Outcome Measures

Number of Hospitalizations for Heart Failure [Approximately 4-years]
Number of hospital admissions with a primary diagnosis of 'heart failure' will be reported.
Number of Participants with Below Knee Lower Extremity Amputation Events [Approximately 4-years]
Number of participants with new below-knee lower extremity amputation procedures, excluding recent (within 30 day) revisions will be reported.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

First exposure to the particular drug(s) in database (index date)
Exposure start is between 1 April 2013 and 15 May 2017
At least 365 days of continuous observation time prior to index
At least 1 condition occurrence of 'Type II diabetes' any time in the prior continuous observation time (which is at least 365 days long) before or on the index date (first exposure to the particular drug(s) in database)

For cohort with 'established cardiovascular disease - At least 1 occurrence of 'conditions indicating established cardiovascular disease' on or any time in the prior continuous observation time (which is at least 365 days long) prior to the index date