A novel approach to treatment of hypertension in diabetic patients - a multicenter, double-blind, randomized study comparing the efficacy of combination therapy of Eprosartan versus Ramipril with low-dose Hydrochlorothiazide and Moxonidine on blood pressure levels in patients with hypertension and associated diabetes mellitus type 2 - rationale and design [ISRCTN55725285

Cornel Pater,Katrin Beckmann,Deepak Bhatnagar,Jean-Pascal Berrou,Joachim Luszick

doi:10.1186/1468-6708-5-9

Abstract

Hypertension and diabetes mellitus are closely interrelated and coexist in as many as two-thirds of patients with type 2 diabetes. The consequent risk of such an association is an accelerated development of atherosclerotic cardiovascular disease and nephropathy complications.In choosing an antihypertensive agent, effectiveness needs to be accompanied by favourable metabolic, cardioprotective, and nephroprotective properties. Given the multifactorial nature of hypertension, the approach that has gained widespread agreement is treatment with more than one agent. Agents with different mechanisms of action increase antihypertensive efficacy because of synergistic impacts on the cardiovascular system. Combination therapy allows the use of lower doses of each antihypertensive agent which accounts for the excellent tolerability of combination products.The aim of the present study is to quantify the efficacy of combination therapy of Eprosartan 600 mg respectively Ramipril 5 mg with low-dose Hydrochlorothiazide and Moxonidine on blood pressure levels in patients with essential hypertension and associated diabetes mellitus type 2.The use of monotherapy (Eprosartan or Ramipril) followed by addition of low-dose Hydrochlorothiazide as second agent and of Moxonidine as a third agent will be individualized to the severity of hypertension in the particular patient and to his/her degree of response to current treatment.

Highlights

The clinical combination of hypertension and diabetes carries a particular poor prognosis [1,2,3,4,5,6]
Subjects with blood pressure in the range: BP > 150/90 – ≤ 179/109 mm Hg will be randomly allocated to double-combination therapy (Eprosartan/HCTZ or Ramipril/ HCTZ); 190 subjects will be recruited for each arm
Assuming that 55% of the patients in the Eprosartan/ HCTZ group would reach goal blood pressure as compared with only 40% in the Ramipril/HCTZ group, a 0.05% two-sided significance level with 80% power to detect the targeted 15% difference will imply the need for 346 patients supposed to complete the four-weeks double-combination therapy phase

Summary

Introduction

The clinical combination of hypertension and diabetes carries a particular poor prognosis [1,2,3,4,5,6]. Clinical studies done in individuals with type 2 diabetes and substudies obtained from clinical trials done in the general population have demonstrated that achievement of goal blood pressure (< 130/80 mm Hg) in this patient category is crucial in decreasing the premature morbidity and mortality [7]. The challenge clinicians are facing is to tighten blood pressure control to less than 130/80 mmHg and to adjust initiation of therapy to the severity of hypertension in the individual patient. Findings from large, international outcomes studies as well as guidelines and recommendation of prestigious international scientific bodies have made available consensus recommendations [8,9,10,11,12,13].

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