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

Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00153023
• Other study ID #: 502.396
• Status: Completed
• Phase: Phase 4
• First received: September 9, 2005
• Last updated: November 12, 2013
• Start date: April 2003
• Est. completion date: December 2005

Study information

• Verified date: November 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ministry of HealthGermany: BfArMAustria: SUKL (state institute for drug control)South Africa: Medicines Control CouncilDenmark: Danish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Italy: Ethics CommitteePortugal: INFARMEDTaiwan: Department of HealthAustria: 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
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 885
• Est. completion date: December 2005
• Est. primary completion date: December 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetic Nephropathies
• Hypertension
• Kidney Diseases

Intervention

Drug:
• Telmisartan

• Valsartan

Locations

Country	Name	City	State
Czech Republic	University Hospital St. Anna	Brno
Czech Republic	University Hospital Hradec Kralove	Hradec Kralove
Czech Republic	University Hospital Vihohrady	Prague 10
Czech Republic	General University Hospital	Prague 2
Czech Republic	District Hospital Tabor	Tabor
Czech Republic	Masaryk Hospital	Usti nad Labem
Czech Republic	Hospital Usti nad Orlici	Usti nad Orlici
Denmark	Medical Department	Copenhagen NV
Denmark	Medicinsk afdeling	Fredericia
Denmark	Medicinsk afdeling F, Endokrinologisk	Hiller?d
Denmark	Endokrinologisk afdeling	Hvidovre
Denmark	Medical Department	Roskilde
France	Chu Sud	Amiens
France	Centre Hospitalier	Beauvais
France	Hopital Duchenne	Boulogne sur Mer cedex
France	Hopital Clemenceau	Caen cedex 5
France	Centre Hospitalier	Dunkerque
France	Hopital Albert Michalon	La Tronche
France	Hopital A.Mignot	Le Chesnay
France	Hopital Maison Blanche	Reims
France	Hopital Yves Le Foll	Saint Brieuc cedex 1
France	Hopital Saint Quentin	Saint Quentin
France	Centre Hospitalier	Valenciennes
Germany	Boehringer Ingelheim Investigational Site	Aschaffenburg
Germany	Diabetes Klinik Bad Mergentheim	Bad Mergentheim
Germany	Charite Campus Buch	Berlin
Germany	Institut fur Klinische Forschung	Berlin
Germany	KFH Dialysezentrum	Eberswalde
Germany	Universitatsklinik Heidelberg	Heidelberg
Germany	Boehringer Ingelheim Investigational Site	Karlsruhe
Germany	Institut fur Klinische Forschung	Mainz
Germany	Boehringer Ingelheim Investigational Site	Munster
Germany	Boehringer Ingelheim Investigational Site	Neuwied
Germany	Boehringer Ingelheim Investigational Site	Pirna
Germany	Boehringer Ingelheim Investigational Site	Riesa
Germany	Boehringer Ingelheim Investigational Site	Rosenheim
Germany	Boehringer Ingelheim Investigational Site	Saarbrucken
Germany	Boehringer Ingelheim Investigational Site	Saarlouis
Germany	Boehringer Ingelheim Investigational Site	Sinsheim
Germany	Boehringer Ingelheim Investigational Site	Speyer
Germany	Internist	Wurzburg
Italy	Azienda Ospedaliera Policlinico S. Orsola Malpighi	Bologna
Italy	Ospedali Riuniti di Livorno	Livorno
Italy	Presidio Ospedaliero Campo di Marte	Lucca
Italy	Universita degli Studi "Federico II"	Napoli
Italy	Azienda Ospedaliera di Padova	Padova
Italy	IRCCS Policlinico S.Matteo	Pavia
Italy	Policlinico Monteluce	Perugia
Italy	Azienda Ospedaliera S. Maria degli Angeli	Pordenone
Italy	Ospedale "S. Maria delle Croci"	Ravenna
Italy	Universita Tor Vergata	Roma
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Yonsei University Medical Center	Seoul
Malaysia	Hospital Ipoh	Ipoh, Perak
Malaysia	University Sains Malaysia	Kelantan
Malaysia	Hospital Kuala Lumpur	Kuala Lumpur
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Penang General Hospital	Penang
Malaysia	Hospital Putrajaya	Selangor
Portugal	Centro Hospitalar de Coimbra	Coimbra
Portugal	Hospital Distrital de Faro	Faro
Portugal	Associac?o Protectora dos Diabeticos de Portugal	Lisboa
Portugal	Hospital de Santa Maria	Lisboa
Portugal	Hospital de Santa Marta	Lisboa
Portugal	Hospital Curry Cabral	Lisbon
Portugal	Hospital Pedro Hispano	Matosinhos
Portugal	Hospital de S. Jo?o	Porto
Portugal	Centro Hospitalar Vila Nova de Gaia	Vila Nova de Gaia
Russian Federation	Medical Academy named Sechenova I.M.	Moscow
Russian Federation	Moscow President's Medical Center	Moscow
Russian Federation	National Endocrinology Research Center of Russia	Moscow
Russian Federation	President's Medical Center	Moscow
Russian Federation	Regional Clinical Scientific Research Institute	Moscow
Russian Federation	Russian Academy for Advanced Medical Studies	Moscow
Russian Federation	Russian Cardiology Research Center	Moscow
Russian Federation	Russian State Medical University	Moscow
Russian Federation	Russian State Medical University	Moscow
Russian Federation	Russian State Medical University	Moscow
Russian Federation	City Hospital of Saint Elizaveta	St. Petersburg
Russian Federation	Military Medical Academy	St. Petersburg
Slovakia	NovaMed	Banska Bystrica
Slovakia	Faculty Hospital	Bratislava
Slovakia	Faculty Hospital of L. Derer	Bratislava
Slovakia	Ministry Hospital of Internal Affairs	Bratislava
Slovakia	Diabetologic and Internal Clinic	Lucenec
Slovakia	Faculty Hospital	Nitra
Slovakia	Hospital Nove Mesto	Nove Mesto
Slovakia	Regional Hospital Nove Zamky	Nove Zamky
Slovakia	MSP-DIAGNOSTIK, Ltd.	Trencin
Slovakia	Faculty Hospital Trnava	Trnava
Spain	Hospital Torrecardenas	Almeria
Spain	Hospital Ntra. Sra de Sonsoles	Avila
Spain	Hospital Clinico y Provincial de Barcelona	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital de Basurto	Bilbao
Spain	Hospital Universitario Reina Sofia	Cordoba
Spain	Hospital de Cabuenes	Gijon
Spain	Hospital Virgen del Rocio	Sevilla
Spain	Hospital Universitario La Fe	Valencia
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	Buddhist Tzu Chi Hospital	Hualien City
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Mackay Memorial Hospital	Taipei
Taiwan	Chi Mei Medical Center	Taiwan
Ukraine	Dnyepropyetrovsk Medical Academy	Dnyepropetrovsk
Ukraine	Institute of Diabetic pathology problems	Kharkov
Ukraine	Kharkiv Medical State University	Kharkov
Ukraine	Institute of Cardiology	Kiev
Ukraine	V.P. Komisarenko Institute of Endocrinology and Metabolism	Kiev
Ukraine	Kyiv Clinical Hospital No. 1	Kyiv
Ukraine	Zaporozhye Regional Clinical Hospital	Zaporozhye

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Czech Republic,  Denmark,  France,  Germany,  Italy,  Korea, Republic of,  Malaysia,  Portugal,  Russian Federation,  Slovakia,  Spain,  Taiwan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change from baseline in 24-hour urinary albumin excretion rate (UAER).		Baseline, after 1 year of treatment	No
Secondary	Change from baseline in 24-hour urinary sodium excretion rate.		Baseline, after 1 year of treatment	No
Secondary	Change from baseline in serum creatinine.		Baseline, after 1 year of treatment	No
Secondary	Change from baseline in creatinine clearance		Baseline, after 1 year of treatment	No
Secondary	Change from baseline in estimated glomerular filtration rate (eGFR).		Baseline, after 1 year of treatment	No
Secondary	Change from baseline in plasma asymmetrical dimethylarginine (ADMA) levels.		Baseline, after 1 year of treatment	No
Secondary	Change from baseline in urine 8-iso-prostaglandin F2a levels		Baseline, after 1 year of treatment	No
Secondary	Change from baseline in serum high sensitive C-reactive protein (CRP) levels.		Baseline, after 1 year of treatment	No
Secondary	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	No
Secondary	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	No
Secondary	Change from baseline in insulin sensitivity (Homeostasis Model Assessment (HOMA) index).		Baseline, after 1 year of treatment	No
Secondary	Change from baseline in plasma adiponectin levels.		Baseline, after 1 year of treatment	No
Secondary	Change from baseline in BP endpoints (SBP, DBP and pulse pressure)		Baseline, after 1 year of treatment	No

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