Replication of the CARMELINA Diabetes Trial in Healthcare Claims

NCT03936036 | Completed FDA Drug

• 1 other identifier: 2018P002966-DUP-CARMELINA
• Study Type: observational
• Target: 101,830
• 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 118-123 days)

Study Arms (2)

2nd generation sulfonylureas

Reference group

Drug: Sulfonylurea

Linagliptin

Exposure group

Drug: Linagliptin

Interventions

Linagliptin DRUG

Linagliptin dispensing claim is used as the exposure

Linagliptin

Sulfonylurea DRUG

2nd generation sulfonylurea dispensing claim is used as the reference

2nd generation sulfonylureas

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• 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 linagliptin to the 2nd generation sulfonylurea (SU) antidiabetic class as a proxy for placebo. SUs are not known to have an impact on the outcome of interest. In addition, SUs were the most frequent background treatment in CARMELINA (after metformin), and DPP4i and SUs are preferentially prescribed to similarly older patients in real world (Patorno et al., 2019). The patients will be required to have continuous enrollment during the baseline period of 180 days before initiation of linagliptin 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 study follow-up.

You may qualify if:

• Documented diagnosis of T2DM before visit 1 (screening).
• Male or female patients who are drug-naïve or pre-treated with any antidiabetic background therapy, excluding treatment with GLP-1 receptor agonists, DPP-4 inhibitors or SGLT-2 inhibitors if ≥ 7 consecutive days.
• Stable antidiabetic background medication (unchanged daily dose) for at least 8 weeks prior to randomization. If insulin is part of the background therapy, the average daily insulin dose should not have been changed by more than 10% within the 8 weeks prior to randomization compared with the daily insulin dose at randomization.
• HbA1c of ≥ 6.5% and ≤ 10.0% at visit 1 (screening).
• Age ≥ 18 years at visit 1 (screening). For Japan only: Age ≥ 20 years at Visit 1.
• Body Mass Index (BMI) 45 kg/m2 at visit 1 (screening).
• Signed and dated written informed consent by date of visit 1 (screening) in accordance with GCP and local legislation prior to any study related procedure.
• High risk of CV events (I and/or II):
• Albuminuria (UACR ≥ 30 mg/g creatinine or ≥ 30 µg/min \[microgram albumin per minute\] or ≥ 30 mg/24 h \[milligram albumin per 24 hours\] in two out of three unrelated spot urine or timed samples in the last 24 months prior to randomization)\*
• AND previous macrovascular disease, defined as either one or more:
• Confirmed history of MI (\> 2 months prior to Visit 1)
• Advanced coronary artery disease, defined by any one of the following:
• ≥ 50% narrowing of the luminal diameter in 2 or more major coronary arteries by coronary angiography, MRI angiography or CT angiography; Definition of major coronary arteries: LAD (Left Anterior Descending). CX (Circumflex) or RCA (right coronary artery)
• Left main stem coronary artery with ≥ 50% narrowing of the luminal diameter by coronary angiography, MRI angiography or CT angiography;
• Prior percutaneous or surgical revascularization of 2 major coronary arteries at least 2 months prior to Visit 1 (screening);

You may not qualify if:

• Type 1 diabetes mellitus.
• Treatment (≥ 7 consecutive days) with GLP-1 receptor agonists, other DPP-4 inhibitors or SGLT-2 inhibitors prior to informed consent. Note: This also includes clinical trials where these antidiabetic drugs have been provided to the patient.
• Active liver disease or impaired hepatic function, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase (AP) ≥3 x upper limit of normal (ULN) as determined at Visit 1.
• eGFR \<15 ml/min/1.73 m2 (severe renal impairment or ESRD, MDRD formula), as determined during screening at Visit 1 and/or the need for maintenance dialysis.
• Any previous (or planned within next 12 months) bariatric surgery (open or laparoscopic) or intervention (gastric sleeve).
• Pre-planned coronary artery re-vascularisation (PCI, CABG) or any previous PCI and/or CABG ≤ 2 months prior informed consent"
• Known hypersensitivity or allergy to the investigational products or its excipients.
• Any previous or current alcohol or drug abuse that would interfere with trial participation in the opinion of the investigator.
• Participation in another trial with an investigational drug ongoing or within 2 months prior to visit 1 (screening)\*.
• Pre-menopausal women (last menstruation 1 year prior to informed consent) who:
• are nursing or pregnant,
• or are of child-bearing potential and are not practicing an acceptable method of birth control (acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence (if allowed by local authorities), double barrier method and vasectomised partner) or do not plan to continue using acceptable method of birth control throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial.
• Patients considered unreliable by the investigator concerning the requirements for follow- up during the study and/or compliance with study drug administration, have a life expectancy less than 5 years for non-CV causes, or have cancer other than non-melanoma skin cancer within last 3 years, or has any other condition than mentioned which in the opinion of the investigator, would not allow safe participation in the study."
• Acute coronary syndrome (ACS), diagnosed ≤ 2 months prior to visit 1 (screening).
• Stroke or TIA ≤ 3 months prior to visit 1 (screening).

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

Linagliptin; Sulfonylurea Compounds

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinazolines; Urea; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

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)