1 Year Trial Telmisartan 80 mg Versus Valsartan 160 mg in Hypertensive Type 2 Diabetic Patients With Overt Nephropathy

Condition(s) targeted: Diabetic Nephropathies; Hypertension

Intervention: Telmisartan (Drug); Valsartan (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Boehringer Ingelheim Pharmaceuticals

Official(s) and/or principal investigator(s):
Boehringer Ingelheim Study Coordinator, Study Chair, Affiliation: B.I. Pharma GmbH & Co. KG

The general aim of this study is to compare telmisartan 80 mg with valsartan 160 mg in hypertensive patients with type 2 diabetes and overt nephropathy with adjusted blood pressure beyond the target of 130/80 mmHg after one year of treatment.

The primary objective of this study is to show that telmisartan 80 mg is at least as effective (i. e. not inferior) and possibly superior to valsartan 160 mg in reducing 24 hour proteinuria after one year of treatment.

Official title: A Prospective, Randomised, Double-Blind, Double-Dummy, Forced-Titration, Multicentre, Parallel Group, One Year Treatment Trial to Investigate the Efficacy of Telmisartan 80 mg Versus Valsartan 160 mg in Hypertensive Type 2 Diabetic Patients With Overt Nephropathy

Study design: Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Change from baseline (Visit 6) in 24 hour proteinuria, after one year of treatment (study end) with telmisartan 80 mg versus valsartan 160 mg.

Secondary outcome: Change from baseline in 24 h albuminuria, creatinine clearance, estimated GFR, serum creatinine, 24 h sodium excretion, ADMA, 8-iso-prostaglandin F2a, hs CRP Doubling of serum creatinine Composite of cardiovascular morbidity and mortality

Detailed description: This is a randomised, double-blind, double-dummy, forced titration, multicentre, parallel group trial in patients with essential hypertension, diabetes mellitus type 2 and diabetic nephropathy.

After a 4 - 6 weeks Run-in period, patients are randomised to one of the treatment groups and

receive either Telmisartan 40 - 80 mg or Valsartan 80 - 160 mg. The treatment regimen is a

forced titration with the lower dose given for 2 weeks and the higher dose given for the rest of the treatment period summing up to 52 weeks of treatment. During the treatment period, 8 visits to the investigator are scheduled in order to control blood pressure, renal function parameters and safety. In addition, parameters of endothelial function and oxidative stress are measured at baseline, 6 months and after one year of treatment.

Study Hypothesis:

Non-inferiority of telmisartan 80 mg compared to valsartan 160 mg will be tested using the following set of hypotheses:

Null Hypothesis:

The overall mean change from baseline in UPER (24h urinary protein excretion rate) for telmisartan 80 mg is inferior to that for valsartan 160 mg by 0. 5 g/day or more.

Alternative Hypothesis:

The overall mean change from baseline in UPER (24h urinary protein excretion rat e) for telmisartan 80 mg is less than 0. 5 g/day worse than that for valsartan 16 0 mg.

Comparison(s):

In order to test the Non-inferiority hypothesis, Analysis of covariance with treatment and centre as main effects and baseline as a covariate will be performed. Time-to-event data will be analysed using the log-rank test.

Minimum age: 30 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. Type 2 diabetes mellitus

2. Aged 30-70 years of age

3. Hypertension at screening defined as:

1. an average cuff systolic blood pressure >130 mmHg and/or diastolic blood pressure >80 mmHg in untreated patients, or

2. patients receiving antihypertensive therapy (i. e. medications specifically prescribed to treat hypertension)

4. Overt nephropathy defined by 24 hour proteinuria > =900 mg and by serum creatinine below 265 ?mol/l (3. 0 mg/dl)

General University Hospital, Prague 2 128 08, Czech Republic

District Hospital Tabor, Tabor 390 03, Czech Republic

University Hospital Vihohrady, Prague 10 100 34, Czech Republic

University Hospital Hradec Kralove, Hradec Kralove 500 05, Czech Republic

University Hospital St. Anna, Brno 656 91, Czech Republic

Masaryk Hospital, Usti nad Labem 401 13, Czech Republic

Hospital Usti nad Orlici, Usti nad Orlici 562 18, Czech Republic

Medical Department, Roskilde DK-4000, Denmark

Endokrinologisk afdeling, Hvidovre DK-2650, Denmark

Medical Department, Copenhagen NV DK-2400, Denmark

Medicinsk afdeling F, Endokrinologisk, Hiller?d 3400, Denmark

Medicinsk afdeling, Fredericia DK-7000, Denmark

Hopital Clemenceau, Caen cedex 5 14033, France

Hopital Albert Michalon, La Tronche 38700, France

Hopital Yves Le Foll, Saint Brieuc cedex 1 22023, France

Hopital Maison Blanche, Reims 51100, France

Centre Hospitalier, Valenciennes 59322, France

Chu Sud, Amiens 80054, France

Hopital Duchenne, Boulogne sur Mer cedex 62320, France

Hopital A.Mignot, Le Chesnay 78157, France

Centre Hospitalier, Beauvais 60021, France

Hopital Saint Quentin, Saint Quentin 02100, France

Centre Hospitalier, Dunkerque 59240, France

Boehringer Ingelheim Investigational Site, Rosenheim 83022, Germany

Boehringer Ingelheim Investigational Site, Aschaffenburg 63739, Germany

Boehringer Ingelheim Investigational Site, Karlsruhe 76133, Germany

Internist, Wurzburg 97072, Germany

Boehringer Ingelheim Investigational Site, Pirna 01796, Germany

Boehringer Ingelheim Investigational Site, Riesa 01587, Germany

Boehringer Ingelheim Investigational Site, Saarlouis 66740, Germany

Boehringer Ingelheim Investigational Site, Sinsheim 74889, Germany

Universitatsklinik Heidelberg, Heidelberg 69115, Germany

Boehringer Ingelheim Investigational Site, Saarbrucken 66121, Germany

Charite Campus Buch, Berlin 13125, Germany

Boehringer Ingelheim Investigational Site, Munster 48145, Germany

Institut fur Klinische Forschung, Mainz 55116, Germany

Institut fur Klinische Forschung, Berlin 10115, Germany

Boehringer Ingelheim Investigational Site, Speyer 67346, Germany

KFH Dialysezentrum, Eberswalde 16225, Germany

Diabetes Klinik Bad Mergentheim, Bad Mergentheim 97980, Germany

Boehringer Ingelheim Investigational Site, Neuwied 56564, Germany

IRCCS Policlinico S.Matteo, PAVIA 27100, Italy

Ospedale "S. Maria delle Croci", RAVENNA 48100, Italy

Universita degli Studi "Federico II", NAPOLI 80131, Italy

Azienda Ospedaliera di Padova, PADOVA 35128, Italy

Azienda Ospedaliera Policlinico S. Orsola Malpighi, BOLOGNA 40138, Italy

Policlinico Monteluce, PERUGIA 06100, Italy

Presidio Ospedaliero Campo di Marte, LUCCA 55100, Italy

Ospedali Riuniti di Livorno, LIVORNO 57100, Italy

Universita Tor Vergata, ROMA 00133, Italy

Azienda Ospedaliera S. Maria degli Angeli, PORDENONE 33170, Italy

Yonsei University Medical Center, Seoul, Korea, Republic of

Keimyung University Dongsan Medical Center, Daegu 700712, Korea, Republic of

University Malaya Medical Centre, Kuala Lumpur 59100, Malaysia

Hospital Kuala Lumpur, Kuala Lumpur 50586, Malaysia

Penang General Hospital, Penang, Malaysia

University Sains Malaysia, Kelantan 16150, Malaysia

Hospital Putrajaya, Selangor, Malaysia

Hospital Ipoh, Ipoh, Perak 30990, Malaysia

Hospital Pedro Hispano, MATOSINHOS 4460-301, Portugal

Hospital de S. Jo?o, PORTO 4200, Portugal

Hospital de Santa Maria, LISBOA 1169-024, Portugal

Hospital de Santa Marta, LISBOA 1169-024, Portugal

Associac?o Protectora dos Diabeticos de Portugal, LISBOA 1250, Portugal

Hospital Distrital de Faro, FARO 8000-386, Portugal

Centro Hospitalar de Coimbra, Coimbra 3041.853, Portugal

Centro Hospitalar Vila Nova de Gaia, Vila Nova de Gaia 4434-502, Portugal

Hospital Curry Cabral, Lisbon 1050-035, Portugal

Russian State Medical University, Moscow 117485, Russian Federation

Russian State Medical University, Moscow 115516, Russian Federation

Russian State Medical University, Moscow 107066, Russian Federation

President's Medical Center, Moscow 121356, Russian Federation

Medical Academy named Sechenova I.M., Moscow 103030, Russian Federation

Regional Clinical Scientific Research Institute, Moscow 129110, Russian Federation

Russian Cardiology Research Center, Moscow 121552, Russian Federation

National Endocrinology Research Center of Russia, Moscow 117036, Russian Federation

Russian Academy for Advanced Medical Studies, Moscow 125315, Russian Federation

Moscow President's Medical Center, Moscow 129090, Russian Federation

City Hospital of Saint Elizaveta, St. Petersburg 195257, Russian Federation

Military Medical Academy, St. Petersburg 198013, Russian Federation

Faculty Hospital, Bratislava 81369, Slovakia

Faculty Hospital, Nitra 94901, Slovakia

Ministry Hospital of Internal Affairs, Bratislava 812 72, Slovakia

Faculty Hospital of L. Derer, Bratislava 833 05, Slovakia

Regional Hospital Nove Zamky, Nove Zamky 940 52, Slovakia

Diabetologic and Internal Clinic, Lucenec 984 01, Slovakia

MSP-DIAGNOSTIK, Ltd., Trencin 91101, Slovakia

Faculty Hospital Trnava, Trnava 91701, Slovakia

NovaMed, Banska Bystrica 974 05, Slovakia

Hospital Nove Mesto, Nove Mesto 915 01, Slovakia

Hospital Vall d'Hebron, Barcelona 08038, Spain

Hospital Virgen del Rocio, Sevilla 41013, Spain

Hospital de Basurto, Bilbao 48013, Spain

Hospital de Cabuenes, Gijon 33204, Spain

Hospital Universitario La Fe, Valencia 46009, Spain

Hospital Clinico y Provincial de Barcelona, Barcelona 08036, Spain

Hospital Ntra. Sra de Sonsoles, Avila 05071, Spain

Hospital Torrecardenas, Almeria 04009, Spain

Hospital Universitario Reina Sofia, Cordoba 14004, Spain

National Cheng Kung University Hospital, Tainan 70428, Taiwan

Mackay Memorial Hospital, Taipei 104, Taiwan

Chi Mei Medical Center, Taiwan 701, Taiwan

Changhua Christian Hospital, Changhua 500, Taiwan

Buddhist Tzu Chi Hospital, Hualien City 970, Taiwan

Kharkiv Medical State University, Kharkov 61022, Ukraine

Institute of Diabetic pathology problems, Kharkov 61070, Ukraine

Dnyepropyetrovsk Medical Academy, Dnyepropetrovsk 49044, Ukraine

Zaporozhye Regional Clinical Hospital, Zaporozhye 69600, Ukraine

Institute of Cardiology, Kiev 03151, Ukraine

Kyiv Clinical Hospital No. 1, Kyiv 02091, Ukraine

V.P. Komisarenko Institute of Endocrinology and Metabolism, Kiev 04114, Ukraine

Ending date: December 2005
Last updated: April 3, 2008