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A Comparative Effectiveness Study of Major Glycemia-lowering Medications for Treatment of Type 2 Diabetes (GRADE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by GRADE Study Group
Sponsor:
Collaborators:
Becton, Dickinson and Company
Bristol-Myers Squibb
Merck Sharp & Dohme Corp.
Novo Nordisk A/S
Hoffmann-La Roche
Sanofi
Information provided by (Responsible Party):
GRADE Study Group
ClinicalTrials.gov Identifier:
NCT01794143
First received: February 13, 2013
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

The GRADE Study is a pragmatic, unmasked clinical trial that will compare commonly used diabetes medications, when combined with metformin, on glycemia-lowering effectiveness and patient-centered outcomes.


Condition Intervention Phase
Type 2 Diabetes
Comparative Effectiveness of Glycemia-lowering Medications
Drug: Sulfonylurea (glimepiride)
Drug: DPP-4 inhibitor (sitagliptin)
Drug: GLP-1 receptor agonist (liraglutide)
Drug: Insulin (glargine)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study

Resource links provided by NLM:


Further study details as provided by GRADE Study Group:

Primary Outcome Measures:
  • Time to HbA1c>=7%, while receiving metformin and the randomly assigned study medication [ Time Frame: Quarterly for 4 to 7 years ] [ Designated as safety issue: No ]
    The primary metabolic outcome is the time to primary failure defined as an HbA1c>=7% (53mmol/mol), subsequently confirmed.


Secondary Outcome Measures:
  • Time to HbA1c>7.5%, while receiving metformin and the randomly assigned study medication. [ Time Frame: Quarterly for 4 to 7 years ] [ Designated as safety issue: No ]
    The secondary metabolic outcome is time to HbA1c>7.5% (58 mmol/mol), confirmed.


Other Outcome Measures:
  • Time to HbA1c>7.5%, while receiving study medications and basal insulin [ Time Frame: Quarterly for 4 to 7 years ] [ Designated as safety issue: No ]
    The tertially metabolic outcome is the time to a HbA1c>7.5% (58 mmol/mol), confirmed, while receiving metformin, the originally assigned medication and basal insulin.


Estimated Enrollment: 5000
Study Start Date: May 2013
Estimated Primary Completion Date: August 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sulfonylurea (glimepiride)
Sulfonylurea
Drug: Sulfonylurea (glimepiride)
Used in accordance with labeling and/or usual practice.
Other Name: Glimepiride
Active Comparator: DPP-4 inhibitor
DPP-4 inhibitor (sitagliptin)
Drug: DPP-4 inhibitor (sitagliptin)
Used in accordance with labeling and/or usual practice
Other Name: Sitagliptin
Active Comparator: GLP-1 receptor agonist
GLP-1 receptor agonist (liraglutide)
Drug: GLP-1 receptor agonist (liraglutide)
Used in accordance with labeling and/or usual practice.
Other Name: Liraglutide
Active Comparator: Insulin (glargine)
Insulin (glargine), Lantus
Drug: Insulin (glargine)
Used in accordance with labeling and/or usual practice.
Other Name: Lantus

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men or women diagnosed with diabetes at age ≥ 30 years (≥ 20 for American Indians)
  2. Duration of diagnosed diabetes < 10 years
  3. HbA1c criteria (at final run-in visit, ~2 weeks prior to randomization): 6.8-8.5%
  4. Taking a daily dose of ≥ 1000 mg metformin for a minimum of 8 weeks at final run-in
  5. Willingness to administer daily subcutaneous injections, take a second diabetes drug after randomization, potentially initiate insulin and intensify insulin therapy if study metabolic goals are not met, perform self-monitoring of blood glucose
  6. Fluent in either English or Spanish
  7. A negative pregnancy test for all females of childbearing potential (i.e. pre-menopausal, and not surgically sterile)
  8. Provision of signed and dated informed consent prior to any study procedures

Exclusion Criteria:

  1. Suspected type 1 diabetes (lean with polyuria, polydipsia, and weight loss with little response to metformin) or "secondary" diabetes due to specific causes (e.g. previously diagnosed monogenic syndromes, pancreatic surgery, pancreatitis)
  2. Current or previous (within past 6 months) treatment with any diabetes drug/glucose-lowering medication other than metformin
  3. More than 10 years of treatment with metformin at time of randomization screening
  4. History of intolerance or allergy or other contraindications to any of the proposed study medications
  5. Resides in the same household with another GRADE study participant
  6. Current need for any specific glucose-lowering medications solely for other conditions, for example for polycystic ovary syndrome
  7. Symptomatic hyperglycemia requiring immediate therapy during screening or run-in, in the judgment of the physician
  8. A life-threatening event within 30 days prior to screening or currently planned major surgery
  9. Any major cardiovascular event in previous year, including history of myocardial infarction, stroke, or vascular procedure such as coronary artery or peripheral bypass grafting, stent placements (peripheral or coronary) or angioplasty.
  10. Plans for pregnancy during the course of the study for women of child-bearing potential
  11. History of or planning bariatric surgery, including banding procedures or surgical gastric and/or intestinal bypass (if banding removed, may be considered eligible after 1 year)
  12. History of congestive heart failure (NYHA 3 or greater)
  13. History of pancreatitis
  14. History of cancer, other than non-melanoma skin cancer, that required therapy in the 5 years prior to randomization
  15. Personal or family history of MEN-2 or family history of medullary thyroid cancer
  16. Serum creatinine >1.4 mg/dl in women and >1.5 mg/dl in men or end stage renal disease requiring renal replacement therapy
  17. History of severe liver disease or acute hepatitis or ALT > 3 times upper limit of normal
  18. Current alcoholism or excessive alcohol intake
  19. Previous organ transplant
  20. Treatment with oral or systemic glucocorticoids (other than short-term treatment, for example for poison ivy) or disease likely to require periodic or regular glucocorticoid therapy (inhaled steroids are allowed)
  21. Treatment with atypical antipsychotics
  22. History of hemolytic anemia, chronic transfusion requirement, or other condition rendering HbA1c results unreliable as indicator of chronic glucose levels, or hematocrit <35 for males and <33 for females
  23. Clinically or medically unstable with expected survival <1 year
  24. Unwillingness to permit sites to contact the PCP to communicate information about the study and the participant's data
  25. No non-study PCP or inability to identify such a PCP (who will provide non-study care) by the time of final run-in
  26. Participation in another interventional clinical trial
  27. Previous randomization in the GRADE study
  28. In the opinion of the principal investigator (PI), any other factor, including language barrier, likely to limit compliance with the protocol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01794143

Contacts
Contact: Heidi Krause-Steinrauf, MS heidi@bsc.gwu.edu
Contact: Paula McGee, MS Paulaf@bsc.gwu.edu

  Show 36 Study Locations
Sponsors and Collaborators
GRADE Study Group
Becton, Dickinson and Company
Bristol-Myers Squibb
Merck Sharp & Dohme Corp.
Novo Nordisk A/S
Hoffmann-La Roche
Sanofi
Investigators
Study Chair: David M Nathan, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: GRADE Study Group
ClinicalTrials.gov Identifier: NCT01794143     History of Changes
Other Study ID Numbers: GRADE, 1U01DK098246-01
Study First Received: February 13, 2013
Last Updated: July 21, 2014
Health Authority: United States: Data and Safety Monitoring Board

Keywords provided by GRADE Study Group:
Treatment of Type 2 diabetes
Comparative effectiveness research
Clinical trial
Patient-centered outcomes

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glimepiride
Glargine
Sitagliptin
Insulin
Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014