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Diabetes Mellitus, Type 2Statins-DMNCT02518503

High Potency Statins and the Risk of Diabetes

An observational study of Diabetes Mellitus, Type 2 and Cardiovascular Disease, run by Canadian Network for Observational Drug Effect Studies, CNODES.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Statins are a class of cholesterol lowering medications that are prescribed for the prevention and treatment of cardiovascular disease. The purpose of this study is to determine if there is an increased risk of new diabetes when exposed to high potency statins, compared to low potency statins, among patients who had a… Read more about this study

Who is it for?
Ages 40 years and older
What is being tested?
Rosuvastatin (≥10 mg), Atorvastatin (≥20 mg) and Simvastatin (≥40 mg)
How many people
136,966 participants
Where
No sites listed yet
Study dates
Jul 2012to Feb 2013
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: In each jurisdiction, the investigators will assemble a study cohort that includes all patients with a new prescription for a statin, including simvastatin, lovastatin, pravastatin, fluvastatin, atorvastatin, and rosuvastatin between 1 January 1998 (or one year after the beginning of data availability) and 31 March 2011. The date of study cohort entry is defined by the prescription date of the newly-prescribed statin after hospital discharge.

Who may be able to join

  • Admitted to hospital with a diagnosis (principal or secondary) for acute myocardial infarction or stroke or a procedure for coronary artery bypass graft or percutaneous coronary intervention during their stay in hospital, with no record of a diabetes diagnosis during their hospitalization
  • Receipt of a prescription for a statin within 90 days of hospital discharge
  • Patients who are at least 40 years of age at cohort entry
  • Patients with at least one year of history in the database

Who cannot join

  • Patients under the age of 40 (<66 in jurisdictions with drug data for seniors only)
  • Patients with less than one year of history in the database
  • Patients who received any cholesterol lowering drugs or diabetes medication/diagnosis in the previous year

About this study

Official title: Higher Potency Statins and the Risk of New Diabetes: Multicentre, Observational Study of Administrative Databases

Statins are a class of cholesterol lowering medications that are prescribed for the prevention and treatment of cardiovascular disease. The purpose of this study is to determine if there is an increased risk of new diabetes when exposed to high potency statins, compared to low potency statins, among patients who had a recent cardiovascular event or procedure.

The investigators will carry out separate population based cohort studies using administrative health care databases in eight jurisdictions in Canada, the US, and the UK. The cohort will be defined by the initiation of a statin, with follow-up until a diagnosis of incident diabetes or a prescription for insulin or an oral antidiabetic medication. The results from the separate sites will be combined in a meta-analysis to provide an overall assessment of the risk of new onset diabetes in subjects starting a statin.

Read the detailed description

The study objective is to determine whether the use of high potency statins, compared with the use of low potency statins, is associated with an increased risk of incident diabetes following hospitalisation for a cardiovascular event or procedure. The investigators will use a common-protocol approach to conduct retrospective cohort studies using health care data from eight jurisdictions (the Canadian provinces of Alberta, Manitoba, Nova Scotia, Ontario, Quebec, and Saskatchewan, as well as the United States (US) MarketScan and the United Kingdom (UK) Clinical Practice Research Datalink [CPRD]). The Canadian provincial databases contain information on physician billing, diagnoses and procedures from hospital discharge abstracts, and dispensations for prescription drugs at a population level. The CPRD is a clinical database that is representative of the UK population and contains the records for patients seen at over 680 general practitioner practices in the UK; these data will be linked to the Hospital Episode Statistics (HES) database, which contains in-hospital diagnosis and procedure data. US MarketScan includes individuals and their dependents covered by large U.S. employer health insurance plans, and government and public organizations.

Study population

In each jurisdiction, the investigators will assemble a study cohort that includes all patients with a new prescription for a statin (after hospital discharge), including simvastatin, lovastatin, pravastatin, fluvastatin, atorvastatin, and rosuvastatin, from the earliest availability of data at each site to the last date of available data. The date of study cohort entry is defined by the prescription date of the newly-prescribed statin. Patients will be followed from the date of study cohort entry until an event (defined below) or censoring due to death, departure from the database, 24 months after the initiation of statin treatment, a dispensing for cerivastatin, or the end of the study period (31 March 2011 or the last date of data availability at that site), whichever occurs first. Data from Alberta, Ontario, and Nova Scotia will be restricted to patients aged 65 years and older as prescription data are not available for younger patients.

Case-control selection

The cohort defined above will be analyzed using a nested case-control analysis, where cases are defined as a hospitalization for incident diabetes or the prescription for an insulin or an oral antidiabetic medication. Risk set sampling will be used to randomly select up to 10 controls for each case, matched on sex, age (± two years; however, if no controls are available, within five years), and cohort entry (± 90 days).

Exposure assessment

The exposure categories will be separated by statin potency (high vs. low dose), and the duration of current exposure. For all cases and controls, exposure will be defined hierarchically; more specifically, patients who receive both a high and low potency statin within the same exposure category will be classified as high potency statin users. Current use of a high potency statin will be defined by the last prescription for a high dose statin prior to the index date. Current users will be further classified into three mutually exclusive durations of current exposure (≤120, 121-365, and 366-730 days).

Statistical analyses

Conditional logistic regression will be used to estimate the odds ratios and corresponding 95% confidence intervals (CIs) of the association between statin use and the diabetes endpoint, comparing current use of high potency statins to low potency statins. This is considered the primary analysis. Several sensitivity analyses will be performed to assess the robustness of study results and address some of the study limitations. High dimensional propensity scores will be estimated for all patients in the cohorts using logistic regression. Finally, all site-specific estimates will be meta-analyzed using fixed or random-effects models with inverse variance weighting. The amount of between-site heterogeneity will be estimated using the I square statistic.

Being tested
Rosuvastatin (≥10 mg), Atorvastatin (≥20 mg), Simvastatin (≥40 mg), Fluvastatin, Pravastatin
Keywords
Diabetes Mellitus, Statins, HMG-CoA reductase inhibitors
Medical subject headings
Diabetes Mellitus, Type 2, Cardiovascular Diseases, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Rosuvastatin (≥10 mg)Drug

    Current cumulative exposure to high dose rosuvastatin (ATC C10AA07) will be defined as a prescription for ≥10 mg of rosuvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-<365 days, or 366-730 days).

  • Atorvastatin (≥20 mg)Drug

    Current cumulative exposure to high dose atorvastatin (ATC C10AA05) will be defined as a prescription for ≥20 mg of atorvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-<365 days, or 366-730 days).

  • Simvastatin (≥40 mg)Drug

    Current cumulative exposure to high dose simvastatin (ATC C10AA01) will be defined as a prescription for ≥40 mg of simvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-<365 days, or 366-730 days).

  • FluvastatinDrug

    Current cumulative exposure to fluvastatin (ATC C10AA04) will be defined as a prescription for any dose of fluvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-<365 days, or 366-730 days).

  • PravastatinDrug

    Current cumulative exposure to pravastatin (ATC C10AA03) will be defined as a prescription for any dose of pravastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-<365 days, or 366-730 days).

  • LovastatinDrug

    Current cumulative exposure to lovastatin (ATC C10AA02) will be defined as a prescription for any dose of lovastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-<365 days, or 366-730 days).

  • Rosuvastatin (<10mg)Drug

    Current cumulative exposure to low dose rosuvastatin (ATC C10AA07) will be defined as a prescription for <10mg of rosuvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-<365 days, or 366-730 days).

  • Atorvastatin (<20mg)Drug

    Current cumulative exposure to low dose atorvastatin (ATC C10AA05) will be defined as a prescription for <20 mg of atorvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-<365 days, or 366-730 days).

  • Simvastatin (<40 mg)Drug

    Current cumulative exposure to low dose simvastatin (ATC C10AA01) will be defined as a prescription for <40 mg simvastatin dispensed prior to the index date in one of the following exposure duration categories (≤120 days, 121-<365 days, or 366-730 days).

Study groups in NCT02518503
Study groupRoleWhat they receive
High potency statin usersExposure will be defined as a new prescription for a high dose statin (high doses of rosuvastatin, high doses of atorvastatin, and high doses of simvastatin) between 1 January 1997 and 31 March 2011, or 1 year after the beginning of data availability.
Receives: Drug: Rosuvastatin (≥10 mg); Drug: Atorvastatin (≥20 mg); Drug: Simvastatin (≥40 mg)
Low potency statin usersExposure will be defined as a new prescription for a low dose statin (all doses of fluvastatin, all doses of pravastatin, all doses of lovastatin; low doses of atorvastatin and simvastatin) between 1 January 1997 and 31 of March 2011, or 1 year after the beginning of data availability.
Receives: Drug: Fluvastatin; Drug: Pravastatin; Drug: Lovastatin; Drug: Rosuvastatin (<10mg); Drug: Atorvastatin (<20mg); Drug: Simvastatin (<40 mg)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with Incident type 2 diabetes

    Patients with a first-hospitalization, receiving a principle or secondary diagnosis for diabetes (ICD-9: 250; ICD-10: E10, E11, E12, E13, E14), or a prescription for insulin or an oral antidiabetic medication.

    Measured: Patients will be followed from the date of study cohort entry until either hospitalization for diabetes or censoring (whichever occurs first), or will be assessed for up to 24 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2015 (estimated)
  2. Study startJul 2012
  3. Primary completionFeb 2013
  4. Study completionFeb 2013

Resources

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
136,966 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02518503
Sponsor's protocol ID
Q12-02
Acronym
Statins-DM
Status last verified
Aug 2015
First submitted
4 Aug 2015
Last updated
14 Mar 2016
Results posted
No
Data monitoring committee
No

Publications

  • Dormuth CR, Filion KB, Paterson JM, James MT, Teare GF, Raymond CB, Rahme E, Tamim H, Lipscombe L; Canadian Network for Observational Drug Effect Studies Investigators. Higher potency statins and the risk of new diabetes: multicentre, observational study of administrative databases. BMJ. 2014 May 29;348:g3244. doi: 10.1136/bmj.g3244.

    PubMed 24874977

Questions about this trial

What is this clinical trial studying?

An observational study of Diabetes Mellitus, Type 2 and Cardiovascular Disease, run by Canadian Network for Observational Drug Effect Studies, CNODES.

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 4 inclusion and 3 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 14 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

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?

Number of participants with Incident type 2 diabetes (time frame: Patients will be followed from the date of study cohort entry until either hospitalization for diabetes or censoring (whichever occurs first), or will be assessed for up to 24 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 NCT02518503, which also lists 1 linked publication.

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 14 Mar 2016.

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