A Prospective, Randomised, Double-blind, Double-dummy, Forced-titration, Multicentre, Parallel Group, One Year Treatment Trial to Compare Telmisartan (MICARDIS) 80 mg Versus Losartan (COZAAR) 100 mg, in Hypertensive Type 2 Diabetic Patients With Overt Nephropathy (AMADEO Study)

A Prospective, Randomised, Double-blind, Double-dummy, Forced-titration, Multicentre, Parallel Group, One Year Treatment Trial to Compare MICARDIS® (Telmisartan) 80 mg Versus COZAAR® (Losartan) 100 mg, in Hypertensive Type 2 Diabetic Patients With Overt Nephropathy (AMADEO Study)

A number of blood pressure lowering drugs in the class known as angiotensin receptor blockers (ARB) have been shown to slow the decline in kidney function of patients with type 2 diabetes, high blood pressure, and kidney disease. Losartan (COZAAR), is one such drug. The purpose of this research study is to determine if after one year of treatment telmisartan (MICARDIS, GLIOSARTAN, KINZAL, KINZALMONO, PREDXAL, PRITOR, SAMERTAN, TELMISARTAN) 80 mg, another blood pressure lowering drug from the ARB class, is as effective as losartan (COZAAR) 100 mg in reducing the level of urinary protein (indicative of improved kidney function).

Inclusion criteria:

• Ability to provide written informed consent in accordance with Good Clinical Practice (GCP) and local legislation

• Age 21-80 years

• Clinical history of type 2 diabetes mellitus, as defined by either:

  • Hyperglycaemia not requiring insulin (diet, oral hypoglycaemic agents and metformin if patients serum creatinine levels were within normal limits.)
  • Hyperglycaemia requiring insulin with: no history of diabetic ketoacidosis AND with either the period between diagnosis and insulin usage >1 year or elevated fasting or stimulated C-peptide level

• Glycosylated haemoglobin A1 (HbA1c) ≤10%

• Diabetic nephropathy, as defined by:

  • serum creatinine at Screening (Visit 1) ≤265 μmol/L (3.0 mg/dL) in women and ≤283 μmol/L (3.2 mg/dL) in men
  • urinary protein/creatinine ratio ≥700 mg/g (measured in spot urine) during the run-in phase (Visit 2 or Visit 5 retest)

• Hypertension at screening, as defined by either:

  • Mean systolic blood pressure (SBP) >130 mmHg and/or mean diastolic blood pressure (DBP) >80 mmHg in untreated patients
  • Patients currently receiving antihypertensive medication (i.e. medications specifically prescribed to treat hypertension)

• Ability to stop current antihypertensive therapy with Angiotensin Converting Enzyme Inhibitor (ACE-Is), Angiotensin Receptor Blockers (ARBs) and direct vasodilators, and to stop chronic immunosuppressive therapy and current therapy with metformin without risk to the patient (Investigator's discretion).

• All female patients had to have negative results from the urine pregnancy test (UPT) at Visits 1 and 6 in order to be able to continue in the study.

Exclusion criteria:

• Pre-menopausal women (last menstruation ≤1 year prior to signing informed consent) who:

  • were not surgically sterile or
  • were nursing or pregnant or
  • were of child-bearing potential and were not practicing acceptable methods of birth control, or did not plan to continue practicing an acceptable method throughout the study (Note: Acceptable methods of birth control included transdermal patch, intra-uterine device, oral, implantable or injectable contraceptives) AND did not agree to periodic urine pregnancy testing (UPT) during participation in the study. No exceptions were made.

• Type 1 diabetes mellitus

• Increase of serum creatinine >35% between Visit 1 (Screening) and Visit 5. If creatinine was increased >35% at Visit 5, the measurement was to be repeated within five calendar days and if the increase was confirmed, the patient had to be excluded from the trial for safety reasons.

• Non-diabetic renal disease

• Congestive heart failure (New York Heart Association functional class III or IV)

• Unstable angina, myocardial infarction, coronary artery bypass graft surgery, or percutaneous coronary intervention within the last three months prior to signing the informed consent form

• Stroke or transient ischaemic attack within the last six months prior to signing the informed consent form

• Hypertrophic obstructive cardiomyopathy, hemodynamically relevant stenosis of the aortic or mitral valve

• Further exclusion criteria apply