1 / 14

…in an academic collaboration with

…in an academic collaboration with. ISRCTN 51125379 www.dtu.ox.ac.uk/4-T. Collaborative academic and pharmaceutical study Three-year, multi-centre trial of addition of anlogue insulin to oral hypoglycaemic agents in 700 patients with Type 2 diabetes Open-label, three arm comparison of:

miller
Download Presentation

…in an academic collaboration with

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. …in an academic collaboration with ISRCTN 51125379 www.dtu.ox.ac.uk/4-T

  2. Collaborative academic and pharmaceutical study Three-year, multi-centre trial of addition of anlogue insulin to oral hypoglycaemic agents in 700 patients with Type 2 diabetes Open-label, three arm comparison of: Basal insulin, given once (or twice) daily Prandial insulin, given three times daily Biphasic insulin, given twice daily 50 secondary-care based UK clinical centres Funded by Novo Nordisk 4-T Design

  3. 4-T Trial Organisation Steering Committee Overall responsibility for scientific, professionaland operational conduct of the study Diabetes Trials Unit Study Design & Protocol Co-ordinating Centre Web-based data collection Clinical queries Statistical analyses Publication Novo Nordisk Study Design & Protocol Site initiation & monitoring Investigator agreements Ethical & regulatory aspects Study medication SAE reporting DTU CentralLaboratory Clinical Centres

  4. Main decision-making body of the Study Responsible for protocol design Ensure overall scientific, professional and operational conduct Review performance of clinical centres, co-ordinating centre, central laboratory and centre monitors on a monthly basis Steering Committee Remit

  5. Professor Rury Holman (Chair) Dr Jonathan Levy (Co-chair) Dr Andrew Farmer (Academic GP) Ms Joanne Keenan (DTU Project Manager) Dr Melanie Davies (Independent Diabetologist) Mr George Nelson (Patient Representative) Dr Alan McDougall (Novo Nordisk) Dr Henrik Schou (Novo Nordisk) Dr Mari-Anne Gall (Novo Nordisk) Steering Committee Membership

  6. Add prandial insulinif glycaemic target not met† Add midday prandial insulin if glycaemic target not met† R Add basal insulinif glycaemic target not met† Twoyears Threeyears Three Way Randomisation Glycaemic target: HbA1c ≤6.5% Add once (or twice) daily basal insulin* 700 T2DMon OAD Add twice daily biphasic insulin* Add thrice daily prandial insulin* Randomisationvisit Oneyear *progress to more intensive insulin regimen only if clinically necessary †stop sulphonylurea if taken

  7. Impact of adding a single insulin preparation to OHAAbility of the three different analogue insulin preparations to achieve good glycaemic control, defined as HbA1C levels ≤ 6.5 %, evaluated over 12 months Need for more complex insulin regimensLonger term efficacy and durability of the three insulin preparations, as well as the need for a second analogue insulin preparation to be added in order to achieve good glycaemic control, evaluated in the second and third years of the study Insulin dose calculatorStudy data will be used to derive algorithms that estimate individual insulin requirements, starting doses and titration steps 4-T Main Study Objectives

  8. Aged ≥18 years, male and female Type 2 diabetes for at least 12 months On maximal tolerated doses of metformin and sulphonylurea for at least four months Body mass index ≤40 kg/m2 HbA1c 7.0 % to 10.0 % inclusive Written informed consent Major Inclusion Criteria

  9. Taking insulin therapy Taking oral antidiabetic therapy other than sulphonylurea and/or metformin Plasma creatinine >130 µmol/L ALT ≥2x upper limit of normal Life threatening cardiovascular disease Participation in a clinical drug trialwithin the last three months Lactating or potentially pregnant females Major Exclusion Criteria

  10. Primary Outcome and Sample Size • The primary objective is to compare the HbA1c levels achieved by the three insulin regimens • Formal analyses will be performed at one year and at three years, without adjustment for multiple comparisons, as the two phases of the study are regarded as separate experiments • 4-T has 95% power to show equivalence between groups at the 5% level of significance if 233 patients per group are randomised, assuming an HbA1c standard deviation of 1.1 and a dropout rate that does not exceed 15%

  11. Grade 2:Minorepisode Plasma glucose<3.1 mmol/L (<56 mg/dl) Grade 3:Majorepisode Assistancerequired Three-level Hypoglycaemia Classification Plasma glucose ≥3.1 mmol/L,(≥56 mg/dl)or not measured Grade 1:Symptomsonly Treated bysubject alone Hypoglycaemicepisode

  12. Safety Assessments • Incidence of major hypoglycaemic episodes • Incidence of unexpected and/orserious adverse events (SAEs) • Plasma ALT, creatinine and lipid levels • Stop metformin if plasma creatinine ≥150 µmol/L • Blood pressure

  13. Schedule • The study commenced 1st November 2004 • 50 UK centres have been enrolled • 18 patients per centre will be recruited • One year results expected in 2007 • Three year results expected in 2009

  14. First point of contact/triage for all queries Email: 4-T@dtu.ox.ac.uk Phone: 01865 857 239 Fax: 01865 857 248 Web site: www.dtu.ox.ac.uk/4-T Co-ordinating Centre

More Related