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

Hypertension Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00240422
• Other study ID #: 502.398
• Status: Completed
• Phase: Phase 4
• First received: October 14, 2005
• Last updated: November 7, 2013
• Start date: February 2003
• Est. completion date: July 2004

Study information

• Verified date: November 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Bundesagentur für Arzneimittel und MedizinprodukteFrance: Ministere charge de la santeSpain: Ministerio de sanidad y consumo, subdirecciòn general de medicamentos de uso humano
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: July 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 80 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Hypertension

Intervention

Drug:
• Telmisartan

• Ramipril

Locations

Country	Name	City	State
France	Boehringer Ingelheim Investigational Site	Lyon
France	Boehringer Ingelheim Investigational Site	Montpellier
Germany	Friedrich-Alexander-Universität	Erlangen
Germany	Boehringer Ingelheim Investigational Site	Nürnberg
Germany	Universität Erlangen-Nürnberg	Nürnberg
Spain	Edificio de Medicina Comunitaria	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

France,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline of renal plasma flow (RPF) in response to L-NMMA infusion at the end of treatment.		9 weeks	No
Secondary	Change from baseline of glomerular filtration rate (GFR) in response to L-NMMA infusion at the end of treatment		9 weeks	No
Secondary	Change from baseline of filtration fraction (FF) in response to L-NMMA infusion at the end of treatment.		9 weeks	No
Secondary	Change from baseline of renal vascular resistance (RVR) in response to L-NMMA infusion at the end of treatment.		9 weeks	No
Secondary	Change from baseline of RPF in response to L-arginine infusion at the end of treatment.		9 weeks	No
Secondary	Change from baseline of GFR in response to L-arginine infusion at the end of treatment		9 weeks	No
Secondary	Change from baseline of FF in response to L-arginine infusion at the end of treatment.		9 weeks	No
Secondary	Change from baseline of RVR in response to L-arginine infusion at the end of treatment.		9 weeks	No
Secondary	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	No
Secondary	Change from baseline of MAP and PR in response to L-arginine infusion at the end of treatment.		9 weeks	No
Secondary	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	No
Secondary	Change from baseline of the pre-L-NMMA RPF at the end of treatment		9 weeks	No
Secondary	Change from baseline of the pre-L-NMMA GFR at the end of treatment		9 weeks	No
Secondary	Change from baseline of the pre-L-NMMA FF at the end of treatment.		9 weeks	No
Secondary	Change from baseline of the pre-L-NMMA RVR at the end of treatment.		9 weeks	No
Secondary	Change from baseline of the urinary excretion parameters creatinine, sodium, potassium, and urea at the end of treatment.		9 weeks	No
Secondary	Blood pressure response and control at the end of treatment		9 weeks	No
Secondary	Change from baseline of central blood pressure and augmentation index (by pulse wave analysis) at the end of treatment.		9 weeks	No
Secondary	Change from baseline of RPF in response to Vitamin C infusion at the end of treatment		9 weeks	No
Secondary	Change from baseline of GFR in response to Vitamin C infusion at the end of treatment		9 weeks	No
Secondary	Change from baseline of FF in response to Vitamin C infusion at the end of treatment.		9 weeks	No
Secondary	Change from baseline of RVR in response to Vitamin C infusion at the end of treatment.		9 weeks	No
Secondary	Change from baseline of MAP and PR in response to Vitamin C infusion at the end of treatment.		9 weeks	No
Secondary	Incidence of adverse events		week -2 and 9 weeks	No
Secondary	Changes from base line in routine laboratory data at the end of the study		9 weeks	No
Secondary	Changes in vital signs		9 weeks	No
Secondary	Changes from screening in physical examination at the end of the study		- 4 weeks and 9 weeks	No
Secondary	Changes from screening in ECG at the end of the study		- 4 weeks and 9 weeks	No

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