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

Phase 4

Completed

• Conditions: Diabetic Nephropathies; Hypertension

• Registration Number: NCT00153023
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

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.

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 week 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 (24 hour 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 (24 hour urinary protein excretion rate) for telmisartan 80 mg is less than 0.5 g/day worse than that for valsartan 160 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.

Study Timeline

• Study Start: 2003-04
• Study First Submitted: 2005-09-09
• Study First Submitted QC: 2005-09-09
• Study First Posted: 2005-09-12
• Primary Completion: 2005-12
• Study Completion: 2005-12
• Status Verified: 2013-11
• Last Update Submitted: 2013-11-12
• Last Update Posted: 2013-11-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 885

Inclusion Criteria

1. Type 2 diabetes mellitus

2. Aged 30-70 years of age

3. Hypertension at screening defined as:

   • an average cuff systolic blood pressure > 130 mmHg and/or diastolic blood pressure >80 mmHg in untreated patients OR
   • 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)

Exclusion Criteria

None

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change from baseline (Visit 6) in 24 hour proteinuria, after one year of treatment (study end) with telmisartan 80 mg versus valsartan 160 mg.	Baseline, after 1 year of treatment

Secondary Outcome Measures

Name	Time	Method
Change from baseline in 24-hour urinary albumin excretion rate (UAER).	Baseline, after 1 year of treatment
Change from baseline in 24-hour urinary sodium excretion rate.	Baseline, after 1 year of treatment
Change from baseline in estimated glomerular filtration rate (eGFR).	Baseline, after 1 year of treatment
Time to a composite of a doubling of serum creatinine concentration , end-stage renal disease (ESRD), or all cause death	after 1 year of treatment
Time to a composite of morbidity and mortality from cardiovascular causes (myocardial infarction (MI), stroke, first hospitalisation for heart failure or unstable angina, coronary or peripheral revascularisation).	after 1 year of treatment
Change from baseline in serum creatinine.	Baseline, after 1 year of treatment
Change from baseline in urine 8-iso-prostaglandin F2α levels	Baseline, after 1 year of treatment
Change from baseline in serum high sensitive C-reactive protein (CRP) levels.	Baseline, after 1 year of treatment
Change from baseline in plasma adiponectin levels.	Baseline, after 1 year of treatment
Change from baseline in creatinine clearance	Baseline, after 1 year of treatment
Change from baseline in plasma asymmetrical dimethylarginine (ADMA) levels.	Baseline, after 1 year of treatment
Change from baseline in insulin sensitivity (Homeostasis Model Assessment (HOMA) index).	Baseline, after 1 year of treatment
Change from baseline in BP endpoints (SBP, DBP and pulse pressure)	Baseline, after 1 year of treatment

Trial Locations

Locations (94)

District Hospital Tabor; 🇨🇿 Tabor, Czech Republic

Hopital A.Mignot; 🇫🇷 Le Chesnay, France

University Hospital Hradec Kralove; 🇨🇿 Hradec Kralove, Czech Republic

Chu Sud; 🇫🇷 Amiens, France

University Hospital St. Anna; 🇨🇿 Brno, Czech Republic

University Hospital Vihohrady; 🇨🇿 Prague 10, Czech Republic

Presidio Ospedaliero Campo di Marte; 🇮🇹 Lucca, Italy

Hospital de S. Jo?o; 🇵🇹 Porto, Portugal

Faculty Hospital of L. Derer; 🇸🇰 Bratislava, Slovakia

Russian State Medical University; 🇷🇺 Moscow, Russian Federation

National Endocrinology Research Center of Russia; 🇷🇺 Moscow, Russian Federation

Regional Hospital Nove Zamky; 🇸🇰 Nove Zamky, Slovakia

Hospital Torrecardenas; 🇪🇸 Almeria, Spain

Hospital Putrajaya; 🇲🇾 Selangor, Malaysia

University Malaya Medical Centre; 🇲🇾 Kuala Lumpur, Malaysia

Hospital Distrital de Faro; 🇵🇹 Faro, Portugal

Mackay Memorial Hospital; 🇨🇳 Taipei, Taiwan

V.P. Komisarenko Institute of Endocrinology and Metabolism; 🇺🇦 Kiev, Ukraine

Masaryk Hospital; 🇨🇿 Usti nad Labem, Czech Republic

General University Hospital; 🇨🇿 Prague 2, Czech Republic

Hospital Usti nad Orlici; 🇨🇿 Usti nad Orlici, Czech Republic

University Sains Malaysia; 🇲🇾 Kelantan, Malaysia

Penang General Hospital; 🇲🇾 Penang, Malaysia

Hospital de Santa Marta; 🇵🇹 Lisboa, Portugal

Hospital Pedro Hispano; 🇵🇹 Matosinhos, Portugal

Diabetologic and Internal Clinic; 🇸🇰 Lucenec, Slovakia

Hospital Nove Mesto; 🇸🇰 Nove Mesto, Slovakia

Medical Department; 🇩🇰 Roskilde, Denmark

Endokrinologisk afdeling; 🇩🇰 Hvidovre, Denmark

Diabetes Klinik Bad Mergentheim; 🇩🇪 Bad Mergentheim, Germany

KFH Dialysezentrum; 🇩🇪 Eberswalde, Germany

Medicinsk afdeling F, Endokrinologisk; 🇩🇰 Hiller?d, Denmark

Medicinsk afdeling; 🇩🇰 Fredericia, Denmark

Yonsei University Medical Center; 🇰🇷 Seoul, Korea, Republic of

Hopital Duchenne; 🇫🇷 Boulogne sur Mer cedex, France

Centre Hospitalier; 🇫🇷 Valenciennes, France

Hospital Curry Cabral; 🇵🇹 Lisbon, Portugal

Hopital Clemenceau; 🇫🇷 Caen cedex 5, France

Hopital Albert Michalon; 🇫🇷 La Tronche, France

Hopital Yves Le Foll; 🇫🇷 Saint Brieuc cedex 1, France

Hopital Maison Blanche; 🇫🇷 Reims, France

Hopital Saint Quentin; 🇫🇷 Saint Quentin, France

Boehringer Ingelheim Investigational Site; 🇩🇪 Speyer, Germany

Charite Campus Buch; 🇩🇪 Berlin, Germany

Institut fur Klinische Forschung; 🇩🇪 Mainz, Germany

Universitatsklinik Heidelberg; 🇩🇪 Heidelberg, Germany

Internist; 🇩🇪 Wurzburg, Germany

Azienda Ospedaliera Policlinico S. Orsola Malpighi; 🇮🇹 Bologna, Italy

Ospedali Riuniti di Livorno; 🇮🇹 Livorno, Italy

Universita degli Studi "Federico II"; 🇮🇹 Napoli, Italy

Azienda Ospedaliera di Padova; 🇮🇹 Padova, Italy

Policlinico Monteluce; 🇮🇹 Perugia, Italy

Azienda Ospedaliera S. Maria degli Angeli; 🇮🇹 Pordenone, Italy

IRCCS Policlinico S.Matteo; 🇮🇹 Pavia, Italy

Universita Tor Vergata; 🇮🇹 Roma, Italy

Keimyung University Dongsan Medical Center; 🇰🇷 Daegu, Korea, Republic of

Ospedale "S. Maria delle Croci"; 🇮🇹 Ravenna, Italy

Hospital Ipoh; 🇲🇾 Ipoh, Perak, Malaysia

Hospital Kuala Lumpur; 🇲🇾 Kuala Lumpur, Malaysia

Hospital de Santa Maria; 🇵🇹 Lisboa, Portugal

Centro Hospitalar de Coimbra; 🇵🇹 Coimbra, Portugal

Associac?o Protectora dos Diabeticos de Portugal; 🇵🇹 Lisboa, Portugal

Centro Hospitalar Vila Nova de Gaia; 🇵🇹 Vila Nova de Gaia, Portugal

Medical Academy named Sechenova I.M.; 🇷🇺 Moscow, Russian Federation

President's Medical Center; 🇷🇺 Moscow, Russian Federation

Russian Cardiology Research Center; 🇷🇺 Moscow, Russian Federation

Russian Academy for Advanced Medical Studies; 🇷🇺 Moscow, Russian Federation

Regional Clinical Scientific Research Institute; 🇷🇺 Moscow, Russian Federation

Moscow President's Medical Center; 🇷🇺 Moscow, Russian Federation

Military Medical Academy; 🇷🇺 St. Petersburg, Russian Federation

City Hospital of Saint Elizaveta; 🇷🇺 St. Petersburg, Russian Federation

NovaMed; 🇸🇰 Banska Bystrica, Slovakia

Ministry Hospital of Internal Affairs; 🇸🇰 Bratislava, Slovakia

Faculty Hospital; 🇸🇰 Nitra, Slovakia

MSP-DIAGNOSTIK, Ltd.; 🇸🇰 Trencin, Slovakia

Faculty Hospital Trnava; 🇸🇰 Trnava, Slovakia

Hospital Clinico y Provincial de Barcelona; 🇪🇸 Barcelona, Spain

Hospital Ntra. Sra de Sonsoles; 🇪🇸 Avila, Spain

Hospital Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Universitario Reina Sofia; 🇪🇸 Cordoba, Spain

Hospital Universitario La Fe; 🇪🇸 Valencia, Spain

Hospital de Basurto; 🇪🇸 Bilbao, Spain

Changhua Christian Hospital; 🇨🇳 Changhua, Taiwan

Hospital Virgen del Rocio; 🇪🇸 Sevilla, Spain

Hospital de Cabuenes; 🇪🇸 Gijon, Spain

Buddhist Tzu Chi Hospital; 🇨🇳 Hualien City, Taiwan

Kyiv Clinical Hospital No. 1; 🇺🇦 Kyiv, Ukraine

Chi Mei Medical Center; 🇨🇳 Taiwan, Taiwan

Kharkiv Medical State University; 🇺🇦 Kharkov, Ukraine

Institute of Cardiology; 🇺🇦 Kiev, Ukraine

Dnyepropyetrovsk Medical Academy; 🇺🇦 Dnyepropetrovsk, Ukraine

Institute of Diabetic pathology problems; 🇺🇦 Kharkov, Ukraine

Zaporozhye Regional Clinical Hospital; 🇺🇦 Zaporozhye, Ukraine

National Cheng Kung University Hospital; 🇨🇳 Tainan, Taiwan