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

  Show 111 Study Locations
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:
Diabetic Nephropathies
Hypertension
Kidney Diseases
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Vascular Diseases
Cardiovascular Diseases
Valsartan
Telmisartan
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014