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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.
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.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Telmisartan | Drug | |||
| Ramipril | Drug |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline of renal plasma flow (RPF) in response to L-NMMA infusion at the end of treatment. | 9 weeks |
| Measure | Description | 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 |
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Inclusion Criteria:
Exclusion Criteria: None
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim Study Coordinator | B.I. Pharma GmbH & Co. KG | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Boehringer Ingelheim Investigational Site | Lyon | France | ||||
| Boehringer Ingelheim Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38682786 | Derived | Natale P, Palmer SC, Navaneethan SD, Craig JC, Strippoli GF. Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers for preventing the progression of diabetic kidney disease. Cochrane Database Syst Rev. 2024 Apr 29;4(4):CD006257. doi: 10.1002/14651858.CD006257.pub2. |
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| 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 |
| Montpellier |
| France |
| Friedrich-Alexander-Universität | Erlangen | 91054 | Germany |
| Boehringer Ingelheim Investigational Site | Nuremberg | 90402 | Germany |
| Universität Erlangen-Nürnberg | Nuremberg | 90471 | Germany |
| Edificio de Medicina Comunitaria | Madrid | 28041 | Spain |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000077333 | Telmisartan |
| D017257 | Ramipril |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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