Clinical trial NCT00153023: 1 Year Trial Telmisartan 80 mg Versus Valsartan 160 mg in Hypertensive Type 2 Diabetic Patients With Overt Nephropathy
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 VIVALDI-Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetic Nephropathies
Hypertension
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2005-09-12
Enrollment: 885
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline (Visit 6) in 24 hour proteinuria, after one year of treatment (study end) with telmisartan 80 mg versus valsartan 160 mg.
timeFrame: Baseline, after 1 year of treatment
Secondary outcomes:
measure: Change from baseline in 24-hour urinary albumin excretion rate (UAER).
timeFrame: Baseline, after 1 year of treatment
measure: Change from baseline in 24-hour urinary sodium excretion rate.
timeFrame: Baseline, after 1 year of treatment
measure: Change from baseline in serum creatinine.
timeFrame: Baseline, after 1 year of treatment
measure: Change from baseline in creatinine clearance
timeFrame: Baseline, after 1 year of treatment
measure: Change from baseline in estimated glomerular filtration rate (eGFR).
timeFrame: Baseline, after 1 year of treatment
measure: Change from baseline in plasma asymmetrical dimethylarginine (ADMA) levels.
timeFrame: Baseline, after 1 year of treatment
measure: Change from baseline in urine 8-iso-prostaglandin F2α levels
timeFrame: Baseline, after 1 year of treatment
measure: Change from baseline in serum high sensitive C-reactive protein (CRP) levels.
timeFrame: Baseline, after 1 year of treatment
measure: Time to a composite of a doubling of serum creatinine concentration , end-stage renal disease (ESRD), or all cause death
timeFrame: after 1 year of treatment
measure: 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).
timeFrame: after 1 year of treatment
measure: Change from baseline in insulin sensitivity (Homeostasis Model Assessment (HOMA) index).
timeFrame: Baseline, after 1 year of treatment
measure: Change from baseline in plasma adiponectin levels.
timeFrame: Baseline, after 1 year of treatment
measure: Change from baseline in BP endpoints (SBP, DBP and pulse pressure)
timeFrame: Baseline, after 1 year of treatment
Other outcomes:
Locations:
city: Brno
country: Czech Republic
facility: University Hospital St. Anna
city: Hradec Kralove
country: Czech Republic
facility: University Hospital Hradec Kralove
city: Prague 10
country: Czech Republic
facility: University Hospital Vihohrady
city: Prague 2
country: Czech Republic
facility: General University Hospital
city: Tabor
country: Czech Republic
facility: District Hospital Tabor
city: Usti nad Labem
country: Czech Republic
facility: Masaryk Hospital
city: Usti nad Orlici
country: Czech Republic
facility: Hospital Usti nad Orlici
city: Copenhagen NV
country: Denmark
facility: Medical Department
city: Fredericia
country: Denmark
facility: Medicinsk afdeling
city: Hiller?d
country: Denmark
facility: Medicinsk afdeling F, Endokrinologisk
city: Hvidovre
country: Denmark
facility: Endokrinologisk afdeling
city: Roskilde
country: Denmark
facility: Medical Department
city: Amiens
country: France
facility: Chu Sud
city: Beauvais
country: France
facility: Centre Hospitalier
city: Boulogne sur Mer cedex
country: France
facility: Hopital Duchenne
city: Caen cedex 5
country: France
facility: Hopital Clemenceau
city: Dunkerque
country: France
facility: Centre Hospitalier
city: La Tronche
country: France
facility: Hopital Albert Michalon
city: Le Chesnay
country: France
facility: Hopital A.Mignot
city: Reims
country: France
facility: Hopital Maison Blanche
city: Saint Brieuc cedex 1
country: France
facility: Hopital Yves Le Foll
city: Saint Quentin
country: France
facility: Hopital Saint Quentin
city: Valenciennes
country: France
facility: Centre Hospitalier
city: Aschaffenburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Bad Mergentheim
country: Germany
facility: Diabetes Klinik Bad Mergentheim
city: Berlin
country: Germany
facility: Institut fur Klinische Forschung
city: Berlin
country: Germany
facility: Charite Campus Buch
city: Eberswalde
country: Germany
facility: KFH Dialysezentrum
city: Heidelberg
country: Germany
facility: Universitatsklinik Heidelberg
city: Karlsruhe
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Mainz
country: Germany
facility: Institut fur Klinische Forschung
city: Munster
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Neuwied
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Pirna
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Riesa
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Rosenheim
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Saarbrucken
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Saarlouis
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Sinsheim
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Speyer
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Wurzburg
country: Germany
facility: Internist
city: Bologna
country: Italy
facility: Azienda Ospedaliera Policlinico S. Orsola Malpighi
city: Livorno
country: Italy
facility: Ospedali Riuniti di Livorno
city: Lucca
country: Italy
facility: Presidio Ospedaliero Campo di Marte
city: Napoli
country: Italy
facility: Universita degli Studi "Federico II"
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Pavia
country: Italy
facility: IRCCS Policlinico S.Matteo
city: Perugia
country: Italy
facility: Policlinico Monteluce
city: Pordenone
country: Italy
facility: Azienda Ospedaliera S. Maria degli Angeli
city: Ravenna
country: Italy
facility: Ospedale "S. Maria delle Croci"
city: Roma
country: Italy
facility: Universita Tor Vergata
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Seoul
country: Korea, Republic of
facility: Yonsei University Medical Center
city: Ipoh, Perak
country: Malaysia
facility: Hospital Ipoh
city: Kelantan
country: Malaysia
facility: University Sains Malaysia
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Penang
country: Malaysia
facility: Penang General Hospital
city: Selangor
country: Malaysia
facility: Hospital Putrajaya
city: Coimbra
country: Portugal
facility: Centro Hospitalar de Coimbra
city: Faro
country: Portugal
facility: Hospital Distrital de Faro
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria
city: Lisboa
country: Portugal
facility: Hospital de Santa Marta
city: Lisboa
country: Portugal
facility: Associac?o Protectora dos Diabeticos de Portugal
city: Lisbon
country: Portugal
facility: Hospital Curry Cabral
city: Matosinhos
country: Portugal
facility: Hospital Pedro Hispano
city: Porto
country: Portugal
facility: Hospital de S. Jo?o
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar Vila Nova de Gaia
city: Moscow
country: Russian Federation
facility: Medical Academy named Sechenova I.M.
city: Moscow
country: Russian Federation
facility: Russian State Medical University
city: Moscow
country: Russian Federation
facility: Russian State Medical University
city: Moscow
country: Russian Federation
facility: National Endocrinology Research Center of Russia
city: Moscow
country: Russian Federation
facility: Russian State Medical University
city: Moscow
country: Russian Federation
facility: President's Medical Center
city: Moscow
country: Russian Federation
facility: Russian Cardiology Research Center
city: Moscow
country: Russian Federation
facility: Russian Academy for Advanced Medical Studies
city: Moscow
country: Russian Federation
facility: Moscow President's Medical Center
city: Moscow
country: Russian Federation
facility: Regional Clinical Scientific Research Institute
city: St. Petersburg
country: Russian Federation
facility: City Hospital of Saint Elizaveta
city: St. Petersburg
country: Russian Federation
facility: Military Medical Academy
city: Banska Bystrica
country: Slovakia
facility: NovaMed
city: Bratislava
country: Slovakia
facility: Ministry Hospital of Internal Affairs
city: Bratislava
country: Slovakia
facility: Faculty Hospital
city: Bratislava
country: Slovakia
facility: Faculty Hospital of L. Derer
city: Lucenec
country: Slovakia
facility: Diabetologic and Internal Clinic
city: Nitra
country: Slovakia
facility: Faculty Hospital
city: Nove Mesto
country: Slovakia
facility: Hospital Nove Mesto
city: Nove Zamky
country: Slovakia
facility: Regional Hospital Nove Zamky
city: Trencin
country: Slovakia
facility: MSP-DIAGNOSTIK, Ltd.
city: Trnava
country: Slovakia
facility: Faculty Hospital Trnava
city: Almeria
country: Spain
facility: Hospital Torrecardenas
city: Avila
country: Spain
facility: Hospital Ntra. Sra de Sonsoles
city: Barcelona
country: Spain
facility: Hospital Clinico y Provincial de Barcelona
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Bilbao
country: Spain
facility: Hospital de Basurto
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Gijon
country: Spain
facility: Hospital de Cabuenes
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Hualien City
country: Taiwan
facility: Buddhist Tzu Chi Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
city: Taiwan
country: Taiwan
facility: Chi Mei Medical Center
city: Dnyepropetrovsk
country: Ukraine
facility: Dnyepropyetrovsk Medical Academy
city: Kharkov
country: Ukraine
facility: Kharkiv Medical State University
city: Kharkov
country: Ukraine
facility: Institute of Diabetic pathology problems
city: Kiev
country: Ukraine
facility: Institute of Cardiology
city: Kiev
country: Ukraine
facility: V.P. Komisarenko Institute of Endocrinology and Metabolism
city: Kyiv
country: Ukraine
facility: Kyiv Clinical Hospital No. 1
city: Zaporozhye
country: Ukraine
facility: Zaporozhye Regional Clinical Hospital
Study officials:
affiliation: B.I. Pharma GmbH & Co. KG
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References: