Trial to Compare the Effects of Either Telmisartan (40-80 mg PO Once Daily) or Ramipril (5-10 mg PO Once Daily) on Renal Endothelial Dysfunction in Hypertensive Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00240422
First received: October 14, 2005
Last updated: November 7, 2013
Last verified: November 2013
  Purpose

The primary objective is to evaluate the effect of 9 weeks treatment with either telmisartan or ramipril on NO bioavailability in the renal vasculature, measured as renal plasma flow (RPF) in response to NG-monomethyl-L-arginine (LNMMA) infusion.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Hypertension
Drug: Telmisartan
Drug: Ramipril
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, Randomized, Double-blind, Double-dummy, Forced Titration, Parallel Group Comparison, Multicenter Trial to Compare the Effects of Either Telmisartan (40-80 mg p.o. Once Daily) or Ramipril (5-10 mg p.o. Once Daily) on Renal Endothelial Dysfunction in Hypertensive Patients With Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Change from baseline of renal plasma flow (RPF) in response to L-NMMA infusion at the end of treatment. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline of glomerular filtration rate (GFR) in response to L-NMMA infusion at the end of treatment [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of filtration fraction (FF) in response to L-NMMA infusion at the end of treatment. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of renal vascular resistance (RVR) in response to L-NMMA infusion at the end of treatment. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of RPF in response to L-arginine infusion at the end of treatment. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of GFR in response to L-arginine infusion at the end of treatment [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of FF in response to L-arginine infusion at the end of treatment. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of RVR in response to L-arginine infusion at the end of treatment. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of mean arterial pressure (MAP) and pulse rate (PR) in response to L-NMMA infusion at the end of treatment. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of MAP and PR in response to L-arginine infusion at the end of treatment. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of the laboratory parameters angiotensin II (ANG II), aldosterone, asymmetrical dimethylarginine (ADMA), L-arginine, urinary nitrate/nitrite (UNOx), and urinary albumin excretion at the end of treatment [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of the pre-L-NMMA RPF at the end of treatment [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of the pre-L-NMMA GFR at the end of treatment [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of the pre-L-NMMA FF at the end of treatment. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of the pre-L-NMMA RVR at the end of treatment. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of the urinary excretion parameters creatinine, sodium, potassium, and urea at the end of treatment. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Blood pressure response and control at the end of treatment [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of central blood pressure and augmentation index (by pulse wave analysis) at the end of treatment. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of RPF in response to Vitamin C infusion at the end of treatment [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of GFR in response to Vitamin C infusion at the end of treatment [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of FF in response to Vitamin C infusion at the end of treatment. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of RVR in response to Vitamin C infusion at the end of treatment. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Change from baseline of MAP and PR in response to Vitamin C infusion at the end of treatment. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Incidence of adverse events [ Time Frame: week -2 and 9 weeks ] [ Designated as safety issue: No ]
  • Changes from base line in routine laboratory data at the end of the study [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Changes in vital signs [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Changes from screening in physical examination at the end of the study [ Time Frame: - 4 weeks and 9 weeks ] [ Designated as safety issue: No ]
  • Changes from screening in ECG at the end of the study [ Time Frame: - 4 weeks and 9 weeks ] [ Designated as safety issue: No ]

Enrollment: 96
Study Start Date: February 2003
Estimated Study Completion Date: July 2004
Detailed Description:

This study was designed as a randomised, double-blind, double-dummy, parallel group in hypertensive patients with type 2 diabetes and normo- or microalbuminuria over a treatment period of 9 weeks.

After a 4 week Run-in period, patients will be randomised to one of the treatment groups and receive either Telmisartan 40 - 80 mg or Ramipril 5 - 10 mg. The treatment regimen is a forced titration with the lower dose given for 3 weeks and the higher dose given for the rest of the treatment period summing up to 9 weeks of treatment. During the treatment period, 3 visits to the investigator will be scheduled in order to control blood pressure, renal function parameters and safety. In addition, parameters of endothelial function in the renal vasculature, based on a nephrological clearance investigation and a provocation with L-NMMA will be measured at baseline and after 9 weeks of treatment.

Study Hypothesis:

Due to the exploratory nature of the trial, the primary objective to evaluate the effect on RPF in response to L-NMMA infusion at baseline and after 9 weeks of therapy with either telmisartan 80 mg or ramipril 10 mg was not planned to be addressed by a test of prespecified hypotheses.

Comparison(s):

The change in RPF from baseline (Visit 4) to the end of treatment (Visit 7) in response to L-NMMA infusion was to be calculated as the change from the pre L-NMMA infusion (S1) to the end of the L-NMMA infusion (S2). A comparison of treatment groups was to be made using an analysis of covariance (ANCOVA) with pooled centre and treatment included as main effects and RPF (in response to L NMMA infusion) at baseline as a covariate. The treatment group difference, adjusted for the other factors in the model, was to be presented with a corresponding 95% confidence interval (CI) and a test of statistical significance. The model was also to be used to provide analysis results for the within treatment group changes.

  Eligibility

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

Inclusion Criteria:

  • Hypertensive patients aged 30-80 years with type 2 diabetes, normo- or microalbuminuria, GFR > 80 mL/min (Cockroft-Gault)

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: NCT00240422

Locations
France
Boehringer Ingelheim Investigational Site
Lyon, France
Boehringer Ingelheim Investigational Site
Montpellier, France
Germany
Friedrich-Alexander-Universität
Erlangen, Germany, 91054
Universität Erlangen-Nürnberg
Nürnberg, Germany, 90471
Boehringer Ingelheim Investigational Site
Nürnberg, Germany, 90402
Spain
Edificio de Medicina Comunitaria
Madrid, Spain, 28041
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: NCT00240422     History of Changes
Other Study ID Numbers: 502.398
Study First Received: October 14, 2005
Last Updated: November 7, 2013
Health Authority: Germany: Bundesagentur für Arzneimittel und Medizinprodukte
France: Ministere charge de la sante
Spain: Ministerio de sanidad y consumo, subdirecciòn general de medicamentos de uso humano

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypertension
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Vascular Diseases
Cardiovascular Diseases
Ramipril
Telmisartan
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on July 26, 2014