AzTrials
AzTrials

DiabetesNCT04215523

Replication of the DECLARE Diabetes Trial in Healthcare Claims

An observational study of Diabetes, run by Brigham and Women's Hospital at 1 site in United States.

Completed

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

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Diabetes
What is being tested?
Dapagliflozin and DPP-4 inhibitor
How many people
49,790 participants
Where
1 siteUnited States
Study dates
8 Jul 2019to 18 Feb 2021
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 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: This study will involve a new user, parallel group, cohort study design comparing dapagliflozin to the DPP-4 inhibitor (DPP4i) antidiabetic class. DPP4is serve as a proxy for placebo, since this class of antidiabetic drugs is not known to have an impact on the outcome of interest. The comparison against DPP4 inhibitors is the primary comparison. The patients will be required to have continuous enrollment during the baseline period of 180 days before initiation of canagliflozin or a comparator drug (cohort entry date). Follow-up for the outcomes (a. 3P-MACE and b. composite of heart failure hospitalization/all-cause mortality), begins the day after drug initiation. As in the trial, patients are allowed to take other antidiabetic medications during the study.

Who may be able to join

  • Provision of informed consent prior to any study specific procedures (including run-in)
  • Female or male aged ≥ 40 years
  • Diagnosed with T2DM
  • High Risk for CV event defined as having either established CV disease and/or multiple risk factors:
  • Established CV Disease (See Appendix E for details) OR No known cardiovascular disease AND at least two cardiovascular risk factors in addition to
  • T2DM, defined as:
Show all 13Show fewer
  • Age > 55 years in men and > 60 in women AND presence of at least 1 of the following additional risk factors (see Appendix E for details)
  • Dyslipidemia
  • Hypertension
  • Tobacco use
  • WOCBP must take precautions to avoid pregnancy throughout the study and for 4 weeks after intake of the last dose.
  • WOCBP must have a negative urine pregnancy test. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal.
  • WOCBP must be willing to use a medically accepted method of contraception that is considered reliable in the judgment of the Investigator. For inclusion in the optional genetic research, patients must fulfill the criterion specified in

Who cannot join

  • Patients should not meet any exclusion criteria at the time of randomization. If at the time of enrollment, it is known that the patient will not meet criteria after a successful run-in period he/she should not be entered into run in.
  • Use of the following excluded medications:
  • Current or recent (within 24 months) treatment with pioglitazone and/or use of pioglitazone for 2 years or more at any time
  • Current or recent (within 12 months) treatment with rosiglitazone
  • Previous treatment with any SGLT2 inhibitor
  • Any patient currently receiving chronic (>30 consecutive days) treatment with an oral steroid at a dose equivalent to oral prednisolone ≥10 mg (e.g., betamethasone ≥1.2 mg, dexamethasone ≥1.5 mg, hydrocortisone ≥40 mg) per day
Show all 23Show fewer
  • Acute cardiovascular event [e.g., acute coronary syndrome (ACS), transient ischemic attack (TIA), stroke, any revascularization, decompensated HF, sustained tachycardia <8 weeks prior to randomization. Patients with acute cardiovascular events can be enrolled in the run-in period as long as randomization does not occur within 8 weeks of the event.
  • Systolic BP >180 or diastolic BP >100 mmHg at randomization
  • Diagnosis of Type 1 diabetes mellitus, MODY, or secondary diabetes mellitus
  • History of bladder cancer or history of radiation therapy to the lower abdomen or pelvis at any time
  • History of any other malignancy within 5 years (with the exception of successfully treated non-melanoma skin cancers)
  • Chronic cystitis and/or recurrent urinary tract infections (3 or more in the last year)
  • Any conditions that, in the opinion of the Investigator, may render the patient unable to complete the study including but not limited to cardiovascular (NYHA class IV CHF, recurrent ventricular arrhythmias) or non-cardiovascular disease (e.g., active malignancy with the exception of basal cell carcinoma, cirrhosis, chronic lung disease, severe autoimmune disease) and/or a likely fatal outcome within 5 years
  • Pregnant or breast-feeding patients
  • Involvement in the planning and/or conduct of the study or other dapagliflozin studies (applies to AZ, BMS, Hadassah and Thrombolysis in Myocardial Infarction [TIMI] or representative staff and/or staff at the study site)
  • Previous randomization in the present study
  • Active participation in another clinical study with IP and/or investigational device
  • Individuals at risk for poor protocol or medication compliance during run-in period (reasonable compliance defined as 80 - 120%, unless a reason for non-compliance is judged acceptable by the Investigator). If for any reason, the Investigator believes that the patient will not tolerate or be compliant with IP or study procedures, the patient should not be randomized and considered a run-in failure. Patients will be excluded during run-in and should not be randomized if the following are observed from laboratory or observation during enrollment and run-in assessments:
  • HbA1c ≥12% or HbA1c<6.5%
  • AST or ALT >3x ULN or Total bilirubin >2.5 x ULN
  • CrCl < 60 ml/min (based on the Cockroft-Gault equation)
  • Hematuria (confirmed by microscopy at Visit 1) with no explanation as judged by the Investigator up to randomization. If bladder cancer is identified, patients are not eligible to participate.
  • Any reason the Investigator believes the patient is not likely to be compliant with the study medication and protocol.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Brigham & Women's Hospital

    Boston, Massachusetts, 02120

Other trials in United States

About this study

Official title: Replication of the Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 Diabetes Trial in Healthcare Claims

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.

Read the detailed description

This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.

Conditions
Diabetes
Being tested
Dapagliflozin, DPP-4 inhibitor
Medical subject headings
Diabetes Mellitus

What participants receive

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

  • DapagliflozinDrug

    Dapagliflozin dispensing claim for any dose is exposure

  • DPP-4 inhibitorDrug

    DPP4 inhibitor dispensing claim for any dose is reference

Study groups in NCT04215523
Study groupRoleWhat they receive
DapagliflozinExposure group
Receives: Drug: Dapagliflozin
DPP-4 inhibitorReference group
Receives: Drug: DPP-4 inhibitor

What is being measured

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

  1. Composite outcome of Stroke, MI, and Mortality

    Composite outcome of MI, stroke, and mortality - Please refer to uploaded protocol for full definition due to size limitations.

    Measured: Through study completion (a median of 120-140 days)

Timeline

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

  1. First posted2 Jan 2020
  2. Study start8 Jul 2019
  3. Primary completion18 Feb 2021
  4. Study completion18 Feb 2021

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
49,790 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04215523
Sponsor's protocol ID
2018P002966-DUP-DECLARE
Status last verified
Jul 2023
First submitted
30 Dec 2019
Last updated
27 Jul 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 33327727

Questions about this trial

What is this clinical trial studying?

An observational study of Diabetes, 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 13 inclusion and 23 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 27 Jul 2023. 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 outcome of Stroke, MI, and Mortality (time frame: Through study completion (a median of 120-140 days)). 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 NCT04215523, 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 27 Jul 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in