Prediction of Findings From the Ongoing CAROLINA Trial Using Healthcare Database Analyses

Completed

• Conditions: Type 2 Diabetes Mellitus

• Registration Number: NCT03648424
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

This cohort study was initiated to predict the findings of CAROLINA trial in a real world setting using electronic claims data from insurance databases with results anticipated prior to the completion of CAROLINA.

Detailed Description

The CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA) is an ongoing randomized controlled trial (RCT) designed to assess whether linagliptin is non-inferior, and if so, superior compared with glimepiride 1-4 mg once daily with respect to cardiovascular (CV) events in adults with relatively early Type 2 Diabetes at increased risk of CV events and with less than optimized glycaemic control. Given that medications of both classes are currently advocated as second-line therapy after metformin, and since sulfonylureas have been associated with concerns regarding their CV safety, while dipeptidyl peptidase-4 inhibitors have been suggested to exhibit CV benefits in preclinical and mechanistic trials, the results of this trial will provide answers to several clinically relevant questions and have a significant impact on clinical practice.

This cohort study was initiated to predict the findings of CAROLINA trial in a real world setting using electronic claims data from insurance databases with results anticipated prior to the completion of CAROLINA. Trial eligibility criteria were adapted in claims data to generate a comparable study cohort (of linagliptin and glimepiride initiators) to that of the trial population. Using 1:1 propensity score-matching was used to control for \>120 baseline characteristics. Patients were followed up for a composite cardiovascular outcome adapted from the primary end-point of the CAROLINA trial.

Study Timeline

• Study Start: 2011-05-01
• Study First Submitted: 2018-08-24
• Study First Submitted QC: 2018-08-24
• Study First Posted: 2018-08-27
• Primary Completion: 2019-06-01
• Study Completion: 2019-06-01
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-23
• Last Update Posted: 2020-09-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48262

Inclusion Criteria

• Patients with Type 2 diabetes who were new users of Linagliptin or new users of Glimepiride and:

  • Had no more than 3 anti-diabetic drugs including index drug

• AND at elevated risk of cardiovascular (CV) events according to specific criteria:

  • Previous vascular disease

  • Evidence of vascular-related end-organ damage

  • Age ⩾ 70 years

  • ⩾ 2 CV risk factors:

    • Treated hypertension
    • Smoking
    • Using any lipid lowering treatment

• Age ≥ 40 and ≤ 85 years at treatment initiation

Exclusion Criteria

• Patients with Type 1 Diabetes Mellitus
• Previous exposure to dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, thiazolidinediones (TZDs), insulin or sodium glucose co-transporter-2 (SGLT-2s).
• Exclude anti-diabetic background therapy if initiated in 2 months prior
• Morbid obesity or treatment with anti-obesity drugs 3 months prior to treatment initiation
• Severe hyperglycemia
• Active liver disease or impaired hepatic function
• Any previous bariatric surgery
• Coronary artery re-vascularisation ≤ 6 weeks prior to treatment initiation
• Prior hospitalization for congestive heart failure
• Acute or chronic metabolic acidosis
• Hereditary galactose intolerance
• Alcohol or drug abuse within the 3 months prior to treatment initiation
• Use of oral corticosteroids
• Pregnant women
• Patients with cancer
• Acute coronary syndrome ≤ 6 weeks prior to treatment initiation
• Stroke or Transient ischemic attack ≤ 3 months prior to treatment initiation

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Composite Cardiovascular (CV) Outcome	From treatment initiation to end of follow-up, up to 53 months	Composite CV Outcome includes Myocardial infarction, Stroke, hospitalization for unstable angina and Death

Trial Locations

Locations (1)

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States