Replication of the LEADER Diabetes Trial in Healthcare Claims

NCT03936049 | Completed FDA Drug

• 1 other identifier: 2018P002966-DUP-LEADER
• Study Type: observational
• Target: 168,690
• 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)

• 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.

  Through study completion (a median of 154-188 days)

Study Arms (2)

DPP-4 inhibitor

Reference group

Drug: DPP-4 inhibitor

Liraglutide

Exposure group

Drug: Liraglutide

Interventions

Liraglutide DRUG

Liraglutide dispensing claim is used as the exposure group

Liraglutide

DPP-4 inhibitor DRUG

DPP-4 inhibitor dispensing claim is used as the reference group

DPP-4 inhibitor

Eligibility Criteria

• Age: 50 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 liraglutide to the DPP4 inhibitor (DPP4i) antidiabetic class as a proxy for placebo. Both 2nd generation sulfonylureas (SUs) and DPP4is are not known to have an impact on the outcome of interest. The comparison against DPP4i is the primary comparison. Initiators of 2nd generation SUs 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 liraglutide 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:

• Men or women with type 2 diabetes
• Either of the following:
• Prior cardiovascular disease cohort: Age ≥ 50 years at screening, AND at least one of the following:
• Prior MI
• Prior stroke or TIA
• Prior coronary, carotid or peripheral arterial revascularization
• \>50% stenosis of coronary, carotid, or lower extremity arteries coded by Peripheral vascular disease
• Chronic heart failure NYHA class II-III
• CKD stage 3-6 as Chronic renal failure:
• No Prior cardiovascular disease group: Age ≥ 60 years at screening, AND at least one of the following:
• Microalbuminuria or proteinuria
• Hypertension and left ventricular hypertrophy by ECG or imaging
• Ankle-brachial index \<0.9

You may not qualify if:

• Type 1 diabetes
• Use of a GLP-1 receptor agonist (exenatide, liraglutide or other) or pramlintide or any (dipeptidyl peptidase 4 (DPP-4) inhibitor within the 3 months prior to screening
• Use of long-term insulin in 90 days prior
• Diabetic ketoacidosis in 3 months prior to index date as Acute decompensation of glycaemic control requiring immediate intensification of treatment to prevent acute complications of diabetes (e.g., diabetic ketoacidosis) in the previous 3 months
• Inpatient (hospitalization) code for MI, stroke, revascularization, PTCA, CABG IN PRIOR 14 DAYS as An acute coronary or cerebrovascular event in the previous 14 days
• inpatient Heart failure (CHF) as Chronic heart failure NYHA class IV
• ESRD codes as Current continuous renal replacement therapy
• Liver disease as "End stage liver disease, defined as the presence of acute or chronic liver disease and recent history of one or more of the following: ascites, encephalopathy, variceal bleeding, bilirubin ≥ 2.0 mg/dL, albumin level ≤ 3.5 g/dL, prothrombin time ≥ 4 seconds prolonged, international normalised ratio (INR) ≥1.7 or prior liver transplant"
• Organ transplant codes as A prior solid organ transplant or awaiting solid organ transplant
• History of malignant neoplasm in previous 5 years 140.xx-208.xx (except 173.xx, non-melanoma skin cancer)
• Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (FMTC)
• Personal history of non-familial medullary thyroid carcinoma
• Drug abuse or dependence as Known use of non prescribed narcotics or illicit drugs
• Encounter for contraceptive management, Oral contraceptives, and pregnancy as "Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures as required by local law or practice)"

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham And 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

Liraglutide; Dipeptidyl-Peptidase IV Inhibitors

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 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 Women's Hospital

  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: April 29, 2019
• First Posted: May 3, 2019
• Study Start: September 22, 2017
• Primary Completion: February 18, 2021
• Study Completion: February 18, 2021
• Last Updated: July 27, 2023

Record last verified: 2023-07

Locations

US (1)