Replication of the EMPAREG Diabetes Trial in Healthcare Claims

NCT04215536 | Completed FDA Drug

• 1 other identifier: 2018P002966-DUP-EMPAREG
• Study Type: observational
• Target: 103,752
• 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)

DPP4i

Reference group

Drug: DPP-4 inhibitor

Empagliflozin

Exposure group

Drug: Empagliflozin

Interventions

Empagliflozin DRUG

Empagliflozin dispensing claim is exposure

Empagliflozin

DPP-4 inhibitor DRUG

DPP4 inhibitor dispensing claim is reference

DPP4i

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 empagliflozin 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 empagliflozin 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.

You may qualify if:

• All of the following criteria needed to be met:
• Subjects with T2DM on a diet and exercise regimen who are drug-naïve (no anti-diabetes therapy for ≥12 weeks prior to randomization) or treated with any anti-diabetes therapy (except pioglitazone in Japan)
• Drug-naive patients were required to have HbA1c ≥7.0% (≥53 mmol/mol) and ≤9.0% (≤75 mmol/mol) at screening
• Pre-treated patients were required to have HbA1c ≥7.0% (≥53 mmol/mol) and ≤10.0 (≤86 mmol/mol) at screening
• Background anti-diabetes therapy had to be unchanged for ≥12 weeks prior to randomization
• If background anti-diabetes therapy included insulin, insulin dose had to be unchanged by \>10% from the dose at randomization in the previous 12 weeks
• Age ≥18 years (≥20 years in Japan and ≤65 years in India)
• Body mass index ≤45 kg/m2 at screening
• High risk of a cardiovascular event defined as ≥1 of the following:
• Confirmed history of myocardial infarction (\>2 months prior to informed consent)
• Evidence of multivessel coronary artery disease (CAD), in ≥2 major coronary arteries or in the left main coronary artery, irrespective of revascularization status, i.e. one of the following:
• Presence of a significant stenosis (imaging evidence of ≥50% narrowing of the luminal diameter measured during a coronary angiography or a multi-sliced computed tomography \[CT\] angiography)
• Revascularization (percutaneous transluminal coronary angioplasty \[PTCA\] with or without stent, or coronary artery bypass grafting \[CAGB\]) ≥2 months prior to consent
• Combination of revascularization in one major coronary artery ≥2 months prior to consent (PCTA with or without stent, or CABG), and the presence of significant stenosis in another major coronary artery (imaging evidence of ≥50% narrowing of the luminal diameter measured during a coronary angiography or a multi-sliced CT angiography)
• Evidence of a single vessel CAD with the presence of significant stenosis i.e. imaging evidence of ≥50% narrowing of the luminal diameter of one major coronary artery in patients not subsequently successfully revascularized (measured during a coronary angiography or a multi-sliced CT angiography) and one or both of the following:

You may not qualify if:

• Uncontrolled hyperglycemia with glucose \>240 mg/dL (\>13.3 mmol/L) after an overnight fast during placebo run-in and confirmed by a second measurement (not on the same day)
• Indication of liver disease, defined by serum levels of alanine amininotransferase, aspartate aminotransferase, or alkaline phosphatase above 3 x upper limit of normal (ULN) during screening or run-in phase
• Planned cardiac surgery or angioplasty within 3 months
• Estimated glomerular filtration rate \<30 ml/min/1.73m2 (according to the Modification of Diet in Renal Disease equation) at screening or during run-in phase
• Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
• Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells e.g. malaria, babesiosis, hemolytic anemia)
• Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
• Contraindications to background therapy according to the local label
• Treatment with anti-obesity drugs 3 months prior to informed consent or any other treatment at time of screening leading to unstable body weight (e.g. surgery, aggressive diet regimen, etc.)
• Treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent
• Any uncontrolled endocrine disorder except T2DM
• Pre-menopausal women (last menstruation ≤1 year prior to informed consent) who were nursing, pregnant, or of child-bearing potential and were not practicing an acceptable method of birth control, or did not plan to continue using this method throughout the study, or did not agree to submit to periodic pregnancy testing during the trial
• \- Acceptable methods of birth control include tubal ligation, transdermal patch, intrauterine devices/systems, oral, implantable or injectable contraceptives, sexual abstinence, double barrier method, vasectomy of partner
• Alcohol or drug abuse within 3 months of informed consent that would interfere with trial participation or any ongoing condition leading to decreased compliance with study procedures or study drug intake
• Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial or participating in another trial involving an investigational drug and/or follow-up

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

empagliflozin; 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)