Replication of the LEADER Diabetes Trial in Healthcare Claims

NCT ID: NCT03936049

Last Updated: 2023-07-27

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 168690 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-09-22
• Study Completion Date: 2021-02-18

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.

Detailed Description

This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.

Conditions

Diabetes

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

DPP-4 inhibitor

Reference group

DPP-4 inhibitor

Intervention Type: DRUG

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

Liraglutide

Exposure group

Liraglutide

Intervention Type: DRUG

Liraglutide dispensing claim is used as the exposure group

Interventions

Liraglutide

Liraglutide dispensing claim is used as the exposure group

Intervention Type: DRUG

DPP-4 inhibitor

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

For Optum: January 20, 2010-Sep 30, 2017 (end of data availability).

• 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

Exclusion Criteria

• 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)"

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Shirley Vichy Wang

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shirley Wang, PhD, ScM

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham And Women's Hospital

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33327727 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2018P002966-DUP-LEADER

Identifier Type: -

Identifier Source: org_study_id