Emulating the PIONEER6 Diabetes Trial Using Healthcare Claims

NCT ID: NCT06659679

Last Updated: 2025-05-25

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 26126 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-10-24
• Study Completion Date: 2025-03-06

Brief Summary

Investigators are building an empirical evidence base for real world data through large-scale emulation 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 emulate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly emulated 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 emulable 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 emulation for a range of possible reasons and does not provide information on the validity of the original RCT finding.

The PIONEER6 trial, is a is a non-inferiority trial to evaluate the effects of oral semaglutide versus placebo in terms of cardiovascular safety (CV death, nonfatal MI, or nonfatal stroke) in patients with type 2 diabetes.

The database study designed to emulate PIONEER6 will be a new-user active comparative study, where we compare the effect of oral semaglutide versus sitagliptin on MACE outcome among patients with T2DM. Sitagliptin was selected to act as an active-comparator proxy for placebo. Sitagliptin and the class of dipeptidyl peptidase-4 (DPP-4) inhibitors have been demonstrated not to have an effect on MACE in a series of RCTs, and they are used in similar stages of disease/line of therapy as semaglutide, as well as being similarly costly.

Conditions

Diabetes Mellitus, Type 2

Study Design

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

Study Groups

New use of oral semaglutide

Exposure group

New use of oral semaglutide

Intervention Type: DRUG

New use of oral semaglutide dispensing claim is used as the exposure.

New use of sitagliptin

Reference group

New initiation of sitagliptin

Intervention Type: DRUG

New use of sitagliptin dispensing claim is used as the reference.

Interventions

New use of oral semaglutide

New use of oral semaglutide dispensing claim is used as the exposure.

Intervention Type: DRUG

New initiation of sitagliptin

New use of sitagliptin dispensing claim is used as the reference.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Market availability of oral semaglutide in the US began on 19th September 2019.

Optum: Study period between 20th Sept 2019 - 29th February 2024 Marketscan: Study period between 20th Sept 2019 - 31st Dec 2022 Medicare: Study period between 20th Sept 2019 - 31st Dec 2020

• Type 2 diabetes mellitus
• Age above or equal to 50 years at screening and clinical evidence of cardiovascular disease: prior myocardial infarction, prior stroke or prior transient ischemic attack, prior coronary, carotid or peripheral arterial revascularization, more than 50% stenosis on angiography or imaging of coronary, carotid or lower extremities arteries, chronic heart failure - New York Heart Association (NYHA) class II-III, chronic renal impairment documents by estimated eGFR <60ml/min/1.73 m2 per MDRD
• Age 60 years or older with subclinical evidence of cardiovascular disease. Subclinical cardiovascular risk factors as one of the following: persistent microalbuminuria (30-299mg/g) or proteinuria, ankle/brachial index less than 0.9

Exclusion Criteria

• Type 1 diabetes mellitus, secondary or gestational diabetes
• Use of glucagon-like peptide-1 (GLP-1) receptor agonist (exenatide, liraglutide, or other) or pramlintide within 90 days prior to screening
• Use of any dipeptidyl peptidase 4 (DPP-IV) inhibitor within 30 days prior to screening
• History of diabetic ketoacidosis, chronic pancreatitis or idiopathic acute pancreatitis
• Any of the following: myocardial infarction, stroke, or hospitalization for unstable angina or transient ischemic attack within the past 60 days prior to screening
• Chronic heart failure New York Heart Association (NYHA) class IV
• Personal or family history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma
• Chronic hemodialysis or peritoneal dialysis
• End stage liver disease
• A prior solid organ transplant or awaiting solid organ transplant
• Diagnosis of malignant neoplasm in the previous 5 years
• Female of childbearing potential who is pregnant, breast-feeding or intends to become pregnant or is not using an adequate contraceptive method
• Proliferative retinopathy or maculopathy requiring treatment
• History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g., subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)
• Missing age or gender
• Nursing home admission

• Minimum Eligible Age: 50 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

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2018P002966-DUP-PIONEER

Identifier Type: -

Identifier Source: org_study_id