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)

Hypertension Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00168857
• Other study ID #: 502.397
• Status: Completed
• Phase: Phase 4
• Start date: July 9, 2003

Study information

• Verified date: November 2023
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 860
• Est. primary completion date: June 1, 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Nephropathies
• Hypertension
• Kidney Diseases

Intervention

Drug:
• telmisartan

• losartan

Locations

Country	Name	City	State
Argentina	Boehringer Ingelheim Investigational Site	Buenos aIRES
Argentina	Boehringer Ingelheim Investigational Site	Córdoba
Argentina	Clinica Coronel Suarez	Coronel Suarez
Argentina	Boehringer Ingelheim Investigational Site	Paraná
Argentina	Boehringer Ingelheim Investigational Site	Provincia De Buenos Aires
Argentina	Boehringer Ingelheim Investigational Site	Rosario, Santa Fé
Argentina	Hospital San Bernardo	Salta
Argentina	Boehringer Ingelheim Investigational Site	Santa Fe
Australia	Lyell McEwin Hospital Department of medicine	Elizabeth	South Australia
Australia	Geelong Clinical Research Centre	Geelong	Victoria
Australia	Boehringer Ingelheim Investigational Site	Kippa-Ring	Queensland
Australia	Boehringer Ingelheim Investigational Site	Melbourne	Victoria
Brazil	Universidade Federal do Pará	Belém
Brazil	Boehringer Ingelheim Investigational Site	Botucatu
Brazil	Faculdade de Medicina Universidade Federal de Juiz de Fora	Juiz De Fora ¿ MG
Brazil	Boehringer Ingelheim Investigational Site	Vila Clementino, São Paulo
Canada	Boehringer Ingelheim Investigational Site	Calgary	Alberta
Canada	Division of Respirology	Halifax	Nova Scotia
Canada	Boehringer Ingelheim Investigational Site	Kitchener	Ontario
Canada	Boehringer Ingelheim Investigational Site	Laval	Quebec
Canada	Boehringer Ingelheim Investigational Site	London	Ontario
Canada	Credit Valley Hospital	Mississauga	Ontario
Canada	CHUM - Hote-Dieu	Montreal	Quebec
Canada	Hopital Maisonneuve Rosemont	Montreal	Quebec
Canada	Boehringer Ingelheim Investigational Site	Oakville	Ontario
Canada	The Ottawa Hospital - Riverside Campus	Ottawa	Ontario
Canada	Boehringer Ingelheim Investigational Site	Red Deer	Alberta
Canada	Boehringer Ingelheim Investigational Site	Saskatoon	Saskatchewan
Canada	CHUS - Hopital Fleurimont	Sherbrooke	Quebec
Canada	LIfestyle Metabolism Centre - Thornhill	Thornhill	Ontario
Canada	Boehringer Ingelheim Investigational Site	Timmins	Ontario
Canada	Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Sunnybrook & Woman's College Health Science Centre	Toronto	Ontario
Canada	BC Endocrine Research Foundation	Vancouver	British Columbia
Canada	Endocrine Research Society	Vancouver	British Columbia
Canada	Humber River Regional Hospital, Dialysis Unit	Weston	Ontario
Canada	University of Manitoba, Diabetes Research Group	Winnipeg	Manitoba
Korea, Republic of	Dongsan Medical Center	Daegu
Korea, Republic of	National Health Insurance Corporation, Ilsan Hospital	Gyunggido
Korea, Republic of	Yongdong Severance Hospital	Seoul
Mexico	Fracc. Magallanes	Acapulco Guerrero
Mexico	Boehringer Ingelheim Investigational Site	Col. Sección XVI, Deleg. Tlalpan
Mexico	Cardiology	Guadalajara
Mexico	Hospital Civil Nuevo de Guadalajara	Guadalajara
Mexico	Boehringer Ingelheim Investigational Site	Guadalajara, Jalisco
Mexico	Dep of Neurology	Metepec
Mexico	Cardiologia	México, D.F.
New Zealand	Boehringer Ingelheim Investigational Site	Auckland
New Zealand	1st Floor Hagely Hostel	Christchurch
Taiwan	Buddhist Tzu Chi General Hospital	Chiayi
Taiwan	Buddhist Tzu Chi General Hospital	Hualien
Taiwan	Chi Mei Medical Center	Tainan
Taiwan	Cathay General Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei
Thailand	Bumrungrad Hospital	Bangkok
Thailand	Pramongkutklao Hospital	Bangkok
Thailand	Siriraj Hospital, Division of Hypertension	Bangkok
Thailand	Thummasart University Hospital	Bangkok
Thailand	Maharaj Nakom Chiang Mai Hospital	Chiang Mai
Thailand	Srinagarind Hospital	Khon Kaen
United States	Boehringer Ingelheim Investigational Site	Atlanta	Georgia
United States	Medical College of Georgia	Augusta	Georgia
United States	Boehringer Ingelheim Investigational Site	Boston	Massachusetts
United States	University of Vermont	Burlington	Vermont
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia Health Science Center	Charlottesville	Virginia
United States	Rush Presbyterian - St. Lukes Medical Center	Chicago	Illinois
United States	The Cleveland Foundation	Cleveland	Ohio
United States	The University of Texas Southwestern Medical Center	Dallas	Texas
United States	University of Colorado Health Sciences Center	Denver	Colorado
United States	Boehringer Ingelheim Investigational Site	Des Moines	Iowa
United States	Boehringer Ingelheim Investigational Site	Eatontown	New Jersey
United States	Boehringer Ingelheim Investigational Site	Flushing	New York
United States	Boehringer Ingelheim Investigational Site	Gig Harbor	Washington
United States	Boehringer Ingelheim Investigational Site	Hollywood	Florida
United States	Boehringer Ingelheim Investigational Site	Lancaster	California
United States	Boehringer Ingelheim Investigational Site	Largo	Florida
United States	Boehringer Ingelheim Investigational Site	Little Rock	Arkansas
United States	Boehringer Ingelheim Investigational Site	Los Angeles	California
United States	VA of Greater Los Angeles	Los Angeles	California
United States	Clement J. Zablocki Veterans Administration Medical Center	Milwaukee	Wisconsin
United States	Winthrop University Hospital	Mineola	New York
United States	Boehringer Ingelheim Investigational Site	Montgomery	Alabama
United States	Louisiana State University Health Science Center	New Orleans	Louisiana
United States	Harlem Hospital	New York	New York
United States	University of Medicine and Dentistry of New Jersey	Newark	New Jersey
United States	Northport VAMC - Medical Service (111)	Northport	New York
United States	Boehringer Ingelheim Investigational Site	Ocala	Florida
United States	UCI Medical Center	Orange	California
United States	Boehringer Ingelheim Investigational Site	Pembroke Pines	Florida
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	VA Pittsburgh Healthcare System	Pittsburgh	Pennsylvania
United States	Wake Nephrology Associates, PA	Raleigh	North Carolina
United States	Boehringer Ingelheim Investigational Site	San Antonio	Texas
United States	University of Texas Health and Science Center at San Antonio	San Antonio	Texas
United States	VA San Diego Healthcare System	San Diego	California
United States	Boehringer Ingelheim Investigational Site	Santa Ana	California
United States	Boehringer Ingelheim Investigational Site	Seattle	Washington
United States	Boehringer Ingelheim Investigational Site	Shreveport	Louisiana
United States	Boehringer Ingelheim Investigational Site	Springfield	Massachusetts
United States	UCLA Medical Center	Sylmar	California
United States	Boehringer Ingelheim Investigational Site	Tampa	Florida
United States	Torrance Clinical Research	Torrance	California
United States	Boehringer Ingelheim Investigational Site	Towson	Maryland
United States	George Washington University	Washington	District of Columbia
United States	Boehringer Ingelheim Investigational Site	Wheat Ridge	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Korea, Republic of,  Mexico,  New Zealand,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline after one year of treatment in proteinuria (ratio of protein to creatinine as measure in spot urine sample).		Up to 1 year
Secondary	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.		Up to 1 year