Replication of the DECLARE Diabetes Trial in Healthcare Claims

NCT04215523 | Completed FDA Drug

• 1 other identifier: 2018P002966-DUP-DECLARE
• Study Type: observational
• Target: 49,790
• 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)

• Composite outcome of Stroke, MI, and Mortality

  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)

Dapagliflozin

Exposure group

Drug: Dapagliflozin

DPP-4 inhibitor

Reference group

Drug: DPP-4 inhibitor

Interventions

Dapagliflozin DRUG

Dapagliflozin dispensing claim for any dose is exposure

Dapagliflozin

DPP-4 inhibitor DRUG

DPP4 inhibitor dispensing claim for any dose is reference

DPP-4 inhibitor

Eligibility Criteria

• Age: 18 Years - 120 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 dapagliflozin 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. 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 outcomes (a. 3P-MACE and b. composite of heart failure hospitalization/all-cause mortality), 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:

• Provision of informed consent prior to any study specific procedures (including run-in)
• Female or male aged ≥ 40 years
• Diagnosed with T2DM
• High Risk for CV event defined as having either established CV disease and/or multiple risk factors:
• \- Established CV Disease (See Appendix E for details) OR No known cardiovascular disease AND at least two cardiovascular risk factors in addition to
• T2DM, defined as:
• Age \> 55 years in men and \> 60 in women AND presence of at least 1 of the following additional risk factors (see Appendix E for details)
• Dyslipidemia
• Hypertension
• Tobacco use
• WOCBP must take precautions to avoid pregnancy throughout the study and for 4 weeks after intake of the last dose.
• WOCBP must have a negative urine pregnancy test. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal.

You may not qualify if:

• Use of the following excluded medications:
• Current or recent (within 24 months) treatment with pioglitazone and/or use of pioglitazone for 2 years or more at any time
• Current or recent (within 12 months) treatment with rosiglitazone
• Previous treatment with any SGLT2 inhibitor
• Any patient currently receiving chronic (\>30 consecutive days) treatment with an oral steroid at a dose equivalent to oral prednisolone ≥10 mg (e.g., betamethasone ≥1.2 mg, dexamethasone ≥1.5 mg, hydrocortisone ≥40 mg) per day
• Acute cardiovascular event \[e.g., acute coronary syndrome (ACS), transient ischemic attack (TIA), stroke, any revascularization, decompensated HF, sustained tachycardia \<8 weeks prior to randomization. Patients with acute cardiovascular events can be enrolled in the run-in period as long as randomization does not occur within 8 weeks of the event.
• Systolic BP \>180 or diastolic BP \>100 mmHg at randomization
• Diagnosis of Type 1 diabetes mellitus, MODY, or secondary diabetes mellitus
• History of bladder cancer or history of radiation therapy to the lower abdomen or pelvis at any time
• History of any other malignancy within 5 years (with the exception of successfully treated non-melanoma skin cancers)
• Chronic cystitis and/or recurrent urinary tract infections (3 or more in the last year)
• Any conditions that, in the opinion of the Investigator, may render the patient unable to complete the study including but not limited to cardiovascular (NYHA class IV CHF, recurrent ventricular arrhythmias) or non-cardiovascular disease (e.g., active malignancy with the exception of basal cell carcinoma, cirrhosis, chronic lung disease, severe autoimmune disease) and/or a likely fatal outcome within 5 years
• Pregnant or breast-feeding patients
• Involvement in the planning and/or conduct of the study or other dapagliflozin studies (applies to AZ, BMS, Hadassah and Thrombolysis in Myocardial Infarction \[TIMI\] or representative staff and/or staff at the study site)
• Previous randomization in the present study

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

dapagliflozin; Dipeptidyl-Peptidase IV Inhibitors

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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: Associate Professor of Medicine

Study Record Dates

• First Submitted: December 30, 2019
• First Posted: January 2, 2020
• Study Start: July 8, 2019
• Primary Completion: February 18, 2021
• Study Completion: February 18, 2021
• Last Updated: July 27, 2023

Record last verified: 2023-07

Locations

US (1)