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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension; Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Telmisartan; Drug: Ramipril

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.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Lyon, France
    • Boehringer Ingelheim Investigational Site
  • Montpellier, France
    • Boehringer Ingelheim Investigational Site
• Germany
  • Erlangen, Germany, 91054
    • Friedrich-Alexander-Universität
  • Nürnberg, Germany, 90402
    • Boehringer Ingelheim Investigational Site
  • Nürnberg, Germany, 90471
    • Universität Erlangen-Nurnberg
• Spain
  • Madrid, Spain, 28041
    • Edificio de Medicina Comunitaria

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria: None

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline of renal plasma flow (RPF) in response to L-NMMA infusion at the end of treatment.	9 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline of glomerular filtration rate (GFR) in response to L-NMMA infusion at the end of treatment	9 weeks
Change from baseline of filtration fraction (FF) in response to L-NMMA infusion at the end of treatment.	9 weeks
Change from baseline of renal vascular resistance (RVR) in response to L-NMMA infusion at the end of treatment.	9 weeks
Change from baseline of RPF in response to L-arginine infusion at the end of treatment.	9 weeks
Change from baseline of GFR in response to L-arginine infusion at the end of treatment	9 weeks
Change from baseline of FF in response to L-arginine infusion at the end of treatment.	9 weeks
Change from baseline of RVR in response to L-arginine infusion at the end of treatment.	9 weeks
Change from baseline of mean arterial pressure (MAP) and pulse rate (PR) in response to L-NMMA infusion at the end of treatment.	9 weeks
Change from baseline of MAP and PR in response to L-arginine infusion at the end of treatment.	9 weeks
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	9 weeks
Change from baseline of the pre-L-NMMA RPF at the end of treatment	9 weeks
Change from baseline of the pre-L-NMMA GFR at the end of treatment	9 weeks
Change from baseline of the pre-L-NMMA FF at the end of treatment.	9 weeks
Change from baseline of the pre-L-NMMA RVR at the end of treatment.	9 weeks
Change from baseline of the urinary excretion parameters creatinine, sodium, potassium, and urea at the end of treatment.	9 weeks
Blood pressure response and control at the end of treatment	9 weeks
Change from baseline of central blood pressure and augmentation index (by pulse wave analysis) at the end of treatment.	9 weeks
Change from baseline of RPF in response to Vitamin C infusion at the end of treatment	9 weeks
Change from baseline of GFR in response to Vitamin C infusion at the end of treatment	9 weeks
Change from baseline of FF in response to Vitamin C infusion at the end of treatment.	9 weeks
Change from baseline of RVR in response to Vitamin C infusion at the end of treatment.	9 weeks
Change from baseline of MAP and PR in response to Vitamin C infusion at the end of treatment.	9 weeks
Incidence of adverse events	week -2 and 9 weeks
Changes from base line in routine laboratory data at the end of the study	9 weeks
Changes in vital signs	9 weeks
Changes from screening in physical examination at the end of the study	- 4 weeks and 9 weeks
Changes from screening in ECG at the end of the study	- 4 weeks and 9 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start: February 1, 2003
• Study Completion: July 1, 2004

Study Registration Dates

• First Submitted: October 14, 2005
• First Submitted That Met QC Criteria: October 14, 2005
• First Posted (Estimate): October 18, 2005

Study Record Updates

• Last Update Posted (Estimate): November 8, 2013
• Last Update Submitted That Met QC Criteria: November 7, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Telmisartan; Ramipril
• Other Study ID Numbers: 502.398