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

Completed

• Conditions: Diabetes Mellitus, Type 2; Cardiovascular Diseases
• Interventions: Drug: Dipeptidyl Peptidase-4 (DPP-4) Inhibitors; Drug: Empagliflozin; Drug: Canagliflozin; Drug: Dapagliflozin; Drug: Glucagon-like Peptide-1 (GLP-1) Agonist; Drug: Anti-hyperglycemic Agents (AHA); Drug: Thiazolidinediones (TZD); Drug: Sulfonylureas (SU); Drug: Insulin

• Registration Number: NCT03492580
• Lead Sponsor: Janssen Research & Development, LLC

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-02-22
• Study First Submitted: 2018-04-03
• Study First Submitted QC: 2018-04-03
• Primary Completion: 2018-04-06
• Study First Posted: 2018-04-10
• Study Completion: 2018-06-25
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-24
• Last Update Posted: 2018-08-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 714582

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

Exclusion Criteria

• Participants with type 1 diabetes or secondary diabetes prior to or on the index date of exposure were excluded from the study

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cohort 8: Empagliflozin or Dapagliflozin with CVD	Dapagliflozin	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.
Cohort 9: DPP-4 inhibitor (i)/ GLP-1 agonist (a)/ other AHA	Dipeptidyl Peptidase-4 (DPP-4) Inhibitors	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.
Cohort 9: DPP-4 inhibitor (i)/ GLP-1 agonist (a)/ other AHA	Glucagon-like Peptide-1 (GLP-1) Agonist	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.
Cohort 9: DPP-4 inhibitor (i)/ GLP-1 agonist (a)/ other AHA	Anti-hyperglycemic Agents (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.
Cohort 10: DPP-4 (i)/ GLP-1 (a)/ other AHA with CVD	Dipeptidyl Peptidase-4 (DPP-4) Inhibitors	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.
Cohort 10: DPP-4 (i)/ GLP-1 (a)/ other AHA with CVD	Glucagon-like Peptide-1 (GLP-1) Agonist	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.
Cohort 10: DPP-4 (i)/ GLP-1 (a)/ other AHA with CVD	Anti-hyperglycemic Agents (AHA)	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.
Cohort 11: DPP-4 (i),GLP-1 (a),TZD, SU, insulin, other AHA	Dipeptidyl Peptidase-4 (DPP-4) Inhibitors	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.
Cohort 12: DPP-4(i), GLP-1(a), TZD, SU, insulin, AHA with CVD	Anti-hyperglycemic Agents (AHA)	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.
Cohort 12: DPP-4(i), GLP-1(a), TZD, SU, insulin, AHA with CVD	Thiazolidinediones (TZD)	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.
Cohort 12: DPP-4(i), GLP-1(a), TZD, SU, insulin, AHA with CVD	Sulfonylureas (SU)	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.
Cohort 12: DPP-4(i), GLP-1(a), TZD, SU, insulin, AHA with CVD	Insulin	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.
Cohort 11: DPP-4 (i),GLP-1 (a),TZD, SU, insulin, other AHA	Glucagon-like Peptide-1 (GLP-1) Agonist	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.
Cohort 11: DPP-4 (i),GLP-1 (a),TZD, SU, insulin, other AHA	Anti-hyperglycemic Agents (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.
Cohort 11: DPP-4 (i),GLP-1 (a),TZD, SU, insulin, other AHA	Thiazolidinediones (TZD)	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.
Cohort 11: DPP-4 (i),GLP-1 (a),TZD, SU, insulin, other AHA	Sulfonylureas (SU)	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.
Cohort 12: DPP-4(i), GLP-1(a), TZD, SU, insulin, AHA with CVD	Dipeptidyl Peptidase-4 (DPP-4) Inhibitors	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.
Cohort 12: DPP-4(i), GLP-1(a), TZD, SU, insulin, AHA with CVD	Glucagon-like Peptide-1 (GLP-1) Agonist	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.
Cohort 11: DPP-4 (i),GLP-1 (a),TZD, SU, insulin, other AHA	Insulin	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.
Cohort 4: Empagliflozin with CVD	Empagliflozin	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.
Cohort 1: Canagliflozin	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).
Cohort 2: Canagliflozin with Cardiovascular Disease (CVD)	Canagliflozin	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.
Cohort 3: Empagliflozin	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.
Cohort 6: Dapagliflozin with CVD	Dapagliflozin	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.
Cohort 5: Dapagliflozin	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.
Cohort 7: Empagliflozin or Dapagliflozin	Empagliflozin	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.
Cohort 7: Empagliflozin or Dapagliflozin	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.
Cohort 8: Empagliflozin or Dapagliflozin with CVD	Empagliflozin	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.

Primary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Janssen Investigative Site; 🇺🇸 Titusville, New Jersey, United States