Clinical trial NCT03648424: Prediction of Findings From the Ongoing CAROLINA Trial Using Healthcare Database Analyses
Official title: Prediction of Findings From the Ongoing CAROLINA Trial Using Healthcare Database Analyses
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Type 2 Diabetes Mellitus
Keywords: Linagliptin
Cardiovascular Death
Stroke
Myocardial Infarction
Hospitalization for Unstable Angina
Type 2 diabetes mellitus
Glimepiride
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2018-08-27
Enrollment: 48262
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients 40 - 85 years of age with early Type 2 Diabetes mellitus, increased cardiovascular risk or established complications

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.

Eligibility criteria: 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

Primary outcomes:
measure: Composite Cardiovascular (CV) Outcome
timeFrame: From treatment initiation to end of follow-up, up to 53 months
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital, Harvard Medical School
name: Elisabetta Patorno, MD DrPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Patorno E, Schneeweiss S, Gopalakrishnan C, Martin D, Franklin JM. Using Real-World Data to Predict Findings of an Ongoing Phase IV Cardiovascular Outcome Trial: Cardiovascular Safety of Linagliptin Versus Glimepiride. Diabetes Care. 2019 Dec;42(12):2204-2210. doi: 10.2337/dc19-0069. Epub 2019 Jun 25.
citation: 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.