Replication of the LEADER Diabetes Trial in Healthcare Claims

Diabetes Clinical Trial

Official title:

Replication of the LEADER Diabetes Trial in Healthcare Claims

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03936049
• Other study ID #: 2018P002966-DUP-LEADER
• Status: Completed
• Start date: September 22, 2017
• Est. completion date: February 18, 2021

Study information

• Verified date: July 2023
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 168690
• Est. completion date: February 18, 2021
• Est. primary completion date: February 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 120 Years

Eligibility

Please see: https://drive.google.com/drive/folders/1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV for full code and algorithm definitions. Eligible cohort entry dates Market availability of liraglutide in the U.S. started on January 20, 2010. For Marketscan and Medicare: January 20, 2010-Dec 31, 2016 (end of data availability). For Optum: January 20, 2010-Sep 30, 2017 (end of data availability).

Inclusion Criteria:

• 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)"

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus

Intervention

Drug:
• Liraglutide
Liraglutide dispensing claim is used as the exposure group
• DPP-4 inhibitor
DPP-4 inhibitor dispensing claim is used as the reference group

Locations

Country	Name	City	State
United States	Brigham And Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)