Type 2 Diabetes MellitusNCT03648424
Prediction of Findings From the Ongoing CAROLINA Trial Using Healthcare Database Analyses
An observational study of Type 2 Diabetes Mellitus, run by Brigham and Women's Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Type 2 Diabetes Mellitus
- How many people
- 48,262 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2011to 1 Jun 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- All sexes
- Adult, Older adult
Study population: Patients 40 - 85 years of age with early Type 2 Diabetes mellitus, increased cardiovascular risk or established complications
Who may be able to join
- 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
Show all 11Show fewer
- ⩾ 2 CV risk factors:
- Treated hypertension
- Smoking
- Using any lipid lowering treatment
- Age ≥ 40 and ≤ 85 years at treatment initiation
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02120
About this study
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.
Read the 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.
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Linagliptin, Cardiovascular Death, Stroke, Myocardial Infarction, Hospitalization for Unstable Angina, Type 2 diabetes mellitus, Glimepiride
- Medical subject headings
- Diabetes Mellitus, Type 2, Stroke, Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Linagliptin | Patients who initiate Linagliptin with no use in the prior 180 days | |
| Glimepiride | Patients who initiate Glimepiride with no use in the prior 180 days |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite Cardiovascular (CV) Outcome
Composite CV Outcome includes Myocardial infarction, Stroke, hospitalization for unstable angina and Death
Measured: From treatment initiation to end of follow-up, up to 53 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2018
- Study start1 May 2011
- Primary completion1 Jun 2019
- Study completion1 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 48,262 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Elisabetta Patorno, Brigham and Women's Hospital
- Investigators
- Elisabetta Patorno, MD DrPH, Principal investigator, Brigham and Women's Hospital, Harvard Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03648424
- Sponsor's protocol ID
- 2013P002157
- Status last verified
- Sep 2020
- First submitted
- 24 Aug 2018
- Last updated
- 25 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 31239281Franklin 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.
PubMed 33327727
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prediction of Findings From the Ongoing CAROLINA Trial Using Healthcare Database Analyses
- ClinicalTrials.gov ID
- NCT03648424
- Acronym / sponsor ID
- 2013P002157
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Linagliptin, Cardiovascular Death, Stroke, Myocardial Infarction, Hospitalization for Unstable Angina, Type 2 diabetes mellitus, Glimepiride
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 48,262 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 1 May 2011 (actual)
- Primary completion
- 1 Jun 2019 (actual)
- Study completion
- 1 Jun 2019 (actual)
- First posted
- 27 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Linagliptin | – | –Patients who initiate Linagliptin with no use in the prior 180 days |
| Glimepiride | – | –Patients who initiate Glimepiride with no use in the prior 180 days |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Patients 40 - 85 years of age with early Type 2 Diabetes mellitus, increased cardiovascular risk or established complications
Key inclusion criteria (11 listed)
- Patients with Type 2 diabetes who were new users of Linagliptin or new users of Glimepiride and:
- AND at elevated risk of cardiovascular (CV) events according to specific criteria:
- Age ≥ 40 and ≤ 85 years at treatment initiation
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Composite Cardiovascular (CV) Outcome
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2020.
- Results publication: PubMed 31239281Patorno 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.
- Derived from this study: PubMed 33327727Franklin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elisabetta Patorno, MD DrPH principal investigator
Brigham and Women's Hospital, Harvard Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type 2 Diabetes Mellitus, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite Cardiovascular (CV) Outcome (time frame: From treatment initiation to end of follow-up, up to 53 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03648424, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2020.