Clinical trial NCT00168857: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Diabetic Nephropathies
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2005-09-15
Enrollment: 860
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline after one year of treatment in proteinuria (ratio of protein to creatinine as measure in spot urine sample).
timeFrame: Up to 1 year
Secondary outcomes:
measure: Change from baseline after one year of treatment in the following: glomerular filtration rate; serum creatinine; macroalbuminuria; sodium excretion; high sensitive C-reactive protein; serum aldosterone; and other renal and cardiovascular measures.
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Montgomery
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Alabama
city: Little Rock
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Arkansas
city: Lancaster
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: Los Angeles
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: Los Angeles
country: United States
facility: VA of Greater Los Angeles
state: California
city: Orange
country: United States
facility: UCI Medical Center
state: California
city: San Diego
country: United States
facility: VA San Diego Healthcare System
state: California
city: Santa Ana
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: Sylmar
country: United States
facility: UCLA Medical Center
state: California
city: Torrance
country: United States
facility: Torrance Clinical Research
state: California
city: Denver
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: Wheat Ridge
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Colorado
city: Washington
country: United States
facility: George Washington University
state: District of Columbia
city: Hollywood
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Largo
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Ocala
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Pembroke Pines
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Tampa
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Georgia
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Chicago
country: United States
facility: Rush Presbyterian - St. Lukes Medical Center
state: Illinois
city: Des Moines
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Iowa
city: New Orleans
country: United States
facility: Louisiana State University Health Science Center
state: Louisiana
city: Shreveport
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Louisiana
city: Towson
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Maryland
city: Boston
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Springfield
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Eatontown
country: United States
facility: Boehringer Ingelheim Investigational Site
state: New Jersey
city: Newark
country: United States
facility: University of Medicine and Dentistry of New Jersey
state: New Jersey
city: Flushing
country: United States
facility: Boehringer Ingelheim Investigational Site
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New York
country: United States
facility: Harlem Hospital
state: New York
city: Northport
country: United States
facility: Northport VAMC - Medical Service (111)
state: New York
city: Raleigh
country: United States
facility: Wake Nephrology Associates, PA
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: VA Pittsburgh Healthcare System
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
city: San Antonio
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health and Science Center at San Antonio
state: Texas
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia Health Science Center
state: Virginia
city: Gig Harbor
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Washington
city: Seattle
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Washington
city: Milwaukee
country: United States
facility: Clement J. Zablocki Veterans Administration Medical Center
state: Wisconsin
city: Buenos aIRES
country: Argentina
facility: Boehringer Ingelheim Investigational Site
city: Coronel Suarez
country: Argentina
facility: Clinica Coronel Suarez
city: Córdoba
country: Argentina
facility: Boehringer Ingelheim Investigational Site
city: Paraná
country: Argentina
facility: Boehringer Ingelheim Investigational Site
city: Provincia De Buenos Aires
country: Argentina
facility: Boehringer Ingelheim Investigational Site
city: Rosario, Santa Fé
country: Argentina
facility: Boehringer Ingelheim Investigational Site
city: Salta
country: Argentina
facility: Hospital San Bernardo
city: Santa Fe
country: Argentina
facility: Boehringer Ingelheim Investigational Site
city: Kippa-Ring
country: Australia
facility: Boehringer Ingelheim Investigational Site
state: Queensland
city: Elizabeth
country: Australia
facility: Lyell McEwin Hospital Department of medicine
state: South Australia
city: Geelong
country: Australia
facility: Geelong Clinical Research Centre
state: Victoria
city: Melbourne
country: Australia
facility: Boehringer Ingelheim Investigational Site
state: Victoria
city: Belém
country: Brazil
facility: Universidade Federal do Pará
city: Botucatu
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Juiz De Fora ¿ MG
country: Brazil
facility: Faculdade de Medicina Universidade Federal de Juiz de Fora
city: Vila Clementino, São Paulo
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Calgary
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Alberta
city: Red Deer
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: BC Endocrine Research Foundation
state: British Columbia
city: Vancouver
country: Canada
facility: Endocrine Research Society
state: British Columbia
city: Winnipeg
country: Canada
facility: University of Manitoba, Diabetes Research Group
state: Manitoba
city: Halifax
country: Canada
facility: Division of Respirology
state: Nova Scotia
city: Kitchener
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: London
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Mississauga
country: Canada
facility: Credit Valley Hospital
state: Ontario
city: Oakville
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital - Riverside Campus
state: Ontario
city: Thornhill
country: Canada
facility: LIfestyle Metabolism Centre - Thornhill
state: Ontario
city: Timmins
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook & Woman's College Health Science Centre
state: Ontario
city: Weston
country: Canada
facility: Humber River Regional Hospital, Dialysis Unit
state: Ontario
city: Laval
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: CHUM - Hote-Dieu
state: Quebec
city: Montreal
country: Canada
facility: Hopital Maisonneuve Rosemont
state: Quebec
city: Sherbrooke
country: Canada
facility: CHUS - Hopital Fleurimont
state: Quebec
city: Saskatoon
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Saskatchewan
city: Daegu
country: Korea, Republic of
facility: Dongsan Medical Center
city: Gyunggido
country: Korea, Republic of
facility: National Health Insurance Corporation, Ilsan Hospital
city: Seoul
country: Korea, Republic of
facility: Yongdong Severance Hospital
city: Acapulco Guerrero
country: Mexico
facility: Fracc. Magallanes
city: Col. Sección XVI, Deleg. Tlalpan
country: Mexico
facility: Boehringer Ingelheim Investigational Site
city: Guadalajara, Jalisco
country: Mexico
facility: Boehringer Ingelheim Investigational Site
city: Guadalajara
country: Mexico
facility: Cardiology
city: Guadalajara
country: Mexico
facility: Hospital Civil Nuevo de Guadalajara
city: Metepec
country: Mexico
facility: Dep of Neurology
city: México, D.F.
country: Mexico
facility: Cardiologia
city: Auckland
country: New Zealand
facility: Boehringer Ingelheim Investigational Site
city: Christchurch
country: New Zealand
facility: 1st Floor Hagely Hostel
city: Chiayi
country: Taiwan
facility: Buddhist Tzu Chi General Hospital
city: Hualien
country: Taiwan
facility: Buddhist Tzu Chi General Hospital
city: Tainan
country: Taiwan
facility: Chi Mei Medical Center
city: Taipei
country: Taiwan
facility: Cathay General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Bangkok
country: Thailand
facility: Bumrungrad Hospital
city: Bangkok
country: Thailand
facility: Pramongkutklao Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital, Division of Hypertension
city: Bangkok
country: Thailand
facility: Thummasart University Hospital
city: Chiang Mai
country: Thailand
facility: Maharaj Nakom Chiang Mai Hospital
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References:
citation: Bakris G, Burgess E, Weir M, Davidai G, Koval S; AMADEO Study Investigators. Telmisartan is more effective than losartan in reducing proteinuria in patients with diabetic nephropathy. Kidney Int. 2008 Aug;74(3):364-9. doi: 10.1038/ki.2008.204. Epub 2008 May 21.