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

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00153023
First received: September 9, 2005
Last updated: November 12, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Diabetic Nephropathies
Hypertension
Drug: Telmisartan
Drug: Valsartan
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: 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 VIVALDI-Study

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Change from baseline (Visit 6) in 24 hour proteinuria, after one year of treatment (study end) with telmisartan 80 mg versus valsartan 160 mg. [ Time Frame: Baseline, after 1 year of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in 24-hour urinary albumin excretion rate (UAER). [ Time Frame: Baseline, after 1 year of treatment ] [ Designated as safety issue: No ]
  • Change from baseline in 24-hour urinary sodium excretion rate. [ Time Frame: Baseline, after 1 year of treatment ] [ Designated as safety issue: No ]
  • Change from baseline in serum creatinine. [ Time Frame: Baseline, after 1 year of treatment ] [ Designated as safety issue: No ]
  • Change from baseline in creatinine clearance [ Time Frame: Baseline, after 1 year of treatment ] [ Designated as safety issue: No ]
  • Change from baseline in estimated glomerular filtration rate (eGFR). [ Time Frame: Baseline, after 1 year of treatment ] [ Designated as safety issue: No ]
  • Change from baseline in plasma asymmetrical dimethylarginine (ADMA) levels. [ Time Frame: Baseline, after 1 year of treatment ] [ Designated as safety issue: No ]
  • Change from baseline in urine 8-iso-prostaglandin F2α levels [ Time Frame: Baseline, after 1 year of treatment ] [ Designated as safety issue: No ]
  • Change from baseline in serum high sensitive C-reactive protein (CRP) levels. [ Time Frame: Baseline, after 1 year of treatment ] [ Designated as safety issue: No ]
  • Time to a composite of a doubling of serum creatinine concentration , end-stage renal disease (ESRD), or all cause death [ Time Frame: after 1 year of treatment ] [ Designated as safety issue: No ]
  • 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). [ Time Frame: after 1 year of treatment ] [ Designated as safety issue: No ]
  • Change from baseline in insulin sensitivity (Homeostasis Model Assessment (HOMA) index). [ Time Frame: Baseline, after 1 year of treatment ] [ Designated as safety issue: No ]
  • Change from baseline in plasma adiponectin levels. [ Time Frame: Baseline, after 1 year of treatment ] [ Designated as safety issue: No ]
  • Change from baseline in BP endpoints (SBP, DBP and pulse pressure) [ Time Frame: Baseline, after 1 year of treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 885
Study Start Date: April 2003
Estimated Study Completion Date: December 2005
Primary Completion Date: December 2005 (Final data collection date for primary outcome measure)
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

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00153023

  Hide Study Locations
Locations
Czech Republic
University Hospital St. Anna
Brno, Czech Republic, 656 91
University Hospital Hradec Kralove
Hradec Kralove, Czech Republic, 500 05
University Hospital Vihohrady
Prague 10, Czech Republic, 100 34
General University Hospital
Prague 2, Czech Republic, 128 08
District Hospital Tabor
Tabor, Czech Republic, 390 03
Masaryk Hospital
Usti nad Labem, Czech Republic, 401 13
Hospital Usti nad Orlici
Usti nad Orlici, Czech Republic, 562 18
Denmark
Medical Department
Copenhagen NV, Denmark, DK-2400
Medicinsk afdeling
Fredericia, Denmark, DK-7000
Medicinsk afdeling F, Endokrinologisk
Hiller?d, Denmark, 3400
Endokrinologisk afdeling
Hvidovre, Denmark, DK-2650
Medical Department
Roskilde, Denmark, DK-4000
France
Chu Sud
Amiens, France, 80054
Centre Hospitalier
Beauvais, France, 60021
Hopital Duchenne
Boulogne sur Mer cedex, France, 62320
Hopital Clemenceau
Caen cedex 5, France, 14033
Centre Hospitalier
Dunkerque, France, 59240
Hopital Albert Michalon
La Tronche, France, 38700
Hopital A.Mignot
Le Chesnay, France, 78157
Hopital Maison Blanche
Reims, France, 51100
Hopital Yves Le Foll
Saint Brieuc cedex 1, France, 22023
Hopital Saint Quentin
Saint Quentin, France, 02100
Centre Hospitalier
Valenciennes, France, 59322
Germany
Boehringer Ingelheim Investigational Site
Aschaffenburg, Germany, 63739
Diabetes Klinik Bad Mergentheim
Bad Mergentheim, Germany, 97980
Charite Campus Buch
Berlin, Germany, 13125
Institut fur Klinische Forschung
Berlin, Germany, 10115
KFH Dialysezentrum
Eberswalde, Germany, 16225
Universitatsklinik Heidelberg
Heidelberg, Germany, 69115
Boehringer Ingelheim Investigational Site
Karlsruhe, Germany, 76133
Institut fur Klinische Forschung
Mainz, Germany, 55116
Boehringer Ingelheim Investigational Site
Munster, Germany, 48145
Boehringer Ingelheim Investigational Site
Neuwied, Germany, 56564
Boehringer Ingelheim Investigational Site
Pirna, Germany, 01796
Boehringer Ingelheim Investigational Site
Riesa, Germany, 01587
Boehringer Ingelheim Investigational Site
Rosenheim, Germany, 83022
Boehringer Ingelheim Investigational Site
Saarbrucken, Germany, 66121
Boehringer Ingelheim Investigational Site
Saarlouis, Germany, 66740
Boehringer Ingelheim Investigational Site
Sinsheim, Germany, 74889
Boehringer Ingelheim Investigational Site
Speyer, Germany, 67346
Internist
Wurzburg, Germany, 97072
Italy
Azienda Ospedaliera Policlinico S. Orsola Malpighi
Bologna, Italy, 40138
Ospedali Riuniti di Livorno
Livorno, Italy, 57100
Presidio Ospedaliero Campo di Marte
Lucca, Italy, 55100
Universita degli Studi "Federico II"
Napoli, Italy, 80131
Azienda Ospedaliera di Padova
Padova, Italy, 35128
IRCCS Policlinico S.Matteo
Pavia, Italy, 27100
Policlinico Monteluce
Perugia, Italy, 06100
Azienda Ospedaliera S. Maria degli Angeli
Pordenone, Italy, 33170
Ospedale "S. Maria delle Croci"
Ravenna, Italy, 48100
Universita Tor Vergata
Roma, Italy, 00133
Korea, Republic of
Keimyung University Dongsan Medical Center
Daegu, Korea, Republic of, 700712
Yonsei University Medical Center
Seoul, Korea, Republic of
Malaysia
Hospital Ipoh
Ipoh, Perak, Malaysia, 30990
University Sains Malaysia
Kelantan, Malaysia, 16150
University Malaya Medical Centre
Kuala Lumpur, Malaysia, 59100
Hospital Kuala Lumpur
Kuala Lumpur, Malaysia, 50586
Penang General Hospital
Penang, Malaysia
Hospital Putrajaya
Selangor, Malaysia
Portugal
Centro Hospitalar de Coimbra
Coimbra, Portugal, 3041.853
Hospital Distrital de Faro
Faro, Portugal, 8000-386
Hospital de Santa Maria
Lisboa, Portugal, 1169-024
Hospital de Santa Marta
Lisboa, Portugal, 1169-024
Associac?o Protectora dos Diabeticos de Portugal
Lisboa, Portugal, 1250
Hospital Curry Cabral
Lisbon, Portugal, 1050-035
Hospital Pedro Hispano
Matosinhos, Portugal, 4460-301
Hospital de S. Jo?o
Porto, Portugal, 4200
Centro Hospitalar Vila Nova de Gaia
Vila Nova de Gaia, Portugal, 4434-502
Russian Federation
Russian State Medical University
Moscow, Russian Federation, 117485
Russian State Medical University
Moscow, Russian Federation, 115516
Russian State Medical University
Moscow, Russian Federation, 107066
President's Medical Center
Moscow, Russian Federation, 121356
Medical Academy named Sechenova I.M.
Moscow, Russian Federation, 103030
Regional Clinical Scientific Research Institute
Moscow, Russian Federation, 129110
Russian Cardiology Research Center
Moscow, Russian Federation, 121552
National Endocrinology Research Center of Russia
Moscow, Russian Federation, 117036
Russian Academy for Advanced Medical Studies
Moscow, Russian Federation, 125315
Moscow President's Medical Center
Moscow, Russian Federation, 129090
City Hospital of Saint Elizaveta
St. Petersburg, Russian Federation, 195257
Military Medical Academy
St. Petersburg, Russian Federation, 198013
Slovakia
NovaMed
Banska Bystrica, Slovakia, 974 05
Faculty Hospital of L. Derer
Bratislava, Slovakia, 833 05
Ministry Hospital of Internal Affairs
Bratislava, Slovakia, 812 72
Faculty Hospital
Bratislava, Slovakia, 81369
Diabetologic and Internal Clinic
Lucenec, Slovakia, 984 01
Faculty Hospital
Nitra, Slovakia, 94901
Hospital Nove Mesto
Nove Mesto, Slovakia, 915 01
Regional Hospital Nove Zamky
Nove Zamky, Slovakia, 940 52
MSP-DIAGNOSTIK, Ltd.
Trencin, Slovakia, 91101
Faculty Hospital Trnava
Trnava, Slovakia, 91701
Spain
Hospital Torrecardenas
Almeria, Spain, 04009
Hospital Ntra. Sra de Sonsoles
Avila, Spain, 05071
Hospital Clinico y Provincial de Barcelona
Barcelona, Spain, 08036
Hospital Vall d'Hebron
Barcelona, Spain, 08038
Hospital de Basurto
Bilbao, Spain, 48013
Hospital Universitario Reina Sofia
Cordoba, Spain, 14004
Hospital de Cabuenes
Gijon, Spain, 33204
Hospital Virgen del Rocio
Sevilla, Spain, 41013
Hospital Universitario La Fe
Valencia, Spain, 46009
Taiwan
Changhua Christian Hospital
Changhua, Taiwan, 500
Buddhist Tzu Chi Hospital
Hualien City, Taiwan, 970
National Cheng Kung University Hospital
Tainan, Taiwan, 70428
Mackay Memorial Hospital
Taipei, Taiwan, 104
Chi Mei Medical Center
Taiwan, Taiwan, 701
Ukraine
Dnyepropyetrovsk Medical Academy
Dnyepropetrovsk, Ukraine, 49044
Institute of Diabetic pathology problems
Kharkov, Ukraine, 61070
Kharkiv Medical State University
Kharkov, Ukraine, 61022
V.P. Komisarenko Institute of Endocrinology and Metabolism
Kiev, Ukraine, 04114
Institute of Cardiology
Kiev, Ukraine, 03151
Kyiv Clinical Hospital No. 1
Kyiv, Ukraine, 02091
Zaporozhye Regional Clinical Hospital
Zaporozhye, Ukraine, 69600
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Study Coordinator B.I. Pharma GmbH & Co. KG
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00153023     History of Changes
Other Study ID Numbers: 502.396
Study First Received: September 9, 2005
Last Updated: November 12, 2013
Health Authority: Spain: Ministry of Health
Germany: BfArM
Austria: SUKL (state institute for drug control)
South Africa: Medicines Control Council
Denmark: Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: Ethics Committee
Portugal: INFARMED
Taiwan: Department of Health
Austria: Ministry of Health Crae of Ukraine (MoH of Ukraine)
South Korea: Korea Food and Drug Administration (KFDA)
Malaysia: Ministry of Health, National Pharmaceutical Control Bureau (NPCB), 6 main ECs

Additional relevant MeSH terms:
Hypertension
Kidney Diseases
Diabetic Nephropathies
Vascular Diseases
Cardiovascular Diseases
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Valsartan
Telmisartan
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014