Delapril and Manidipine for Nephroprotection in Diabetes (DEMAND)
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 3

Summary: 
      Diabetes mellitus is one of the most common diseases globally, and is considered epidemic in
      many developed and newly industrialized nations. Diabetes mellitus represents the single
      largest cause of end-stage renal disease in the U.S. and Europe. At the same time, the
      primary cause of early death in diabetic patients are cardiovascular complications.
      Experimental and clinical studies found that angiotensin converting enzyme inhibitors (ACEi)
      and calcium channel blockers (CCBs) have a specific renoprotective effect and that this
      effect can be magnified when the two drugs are used in combination. To formally test this
      hypothesis we designed the Delapril and Manidipine for Nephroprotection in Diabetes (DEMAND)
      study, a prospective, randomized, double blind trial aimed to compare the effect of 3 years
      treatment with the ACEi Delapril (30 mg/day), alone or combined to the CCB Manidipine (10
      mg/day), versus conventional (non ACEi, non CCB) therapy on the rate of renal function loss
      and on the incidence of major cardiovascular events in 342 normo- and micro-albuminuric
      hypertensive type 2 diabetic patients.
    

Detailed description: 
      INTRODUCTION Optimal blood pressure, glycemic and lipid control are of utmost importance to
      minimize the incidence and the progression of chronic renal and cardiovascular complications
      in patients with diabetes mellitus type 2. Whether angiotensin converting enzyme (ACE)
      inhibitors alone or combined to calcium channel blockers (CCB) may further reduce the
      incidence and progression of chronic complications is worth investigating.

      AIMS The primary aim of this study is to assess whether at comparable levels of optimal blood
      pressure and metabolic control, the ACE inhibitor delapril alone or in combination with the
      dihydropyridine CCB manidipine slow the rate of glomerular filtration rate (GFR) decline as
      compared with placebo plus conventional antihypertensive therapy in patients with diabetes
      mellitus type 2 and hypertension. The secondary aim of this study is to assess the effects of
      delapril and manidipine on the incidence of major cardiovascular events (acute myocardial
      infarction, ictus or stroke, heart failure requiring hospitalization, revascularization,
      amputation and cardiovascular mortality).

      STUDY POPULATION 342 hypertensive type 2 diabetes patients with normo- or micro-albuminuria.
      STUDY DESIGN This is a multicenter, prospective, randomized, double-blind, placebo-controlled
      study. After a 12-week baseline period in which prohibited antihypertensive treatments (ACE
      inhibitors, angiotensin II receptor antagonists or dihydropyridine calcium channel blockers)
      will be discontinued, patients will be stratified according to their urinary albumin
      excretion rate in normo- and micro-albuminuric and then randomized to delapril alone (30
      mg/day), delapril (30 mg/day) combined with manidipine (10 mg/day) or placebo given once
      daily in the morning for at least three years. During the study, systolic and diastolic blood
      pressure in all treatments groups will be maintained ≤ 120 and 80 mmHg respectively, with
      fixed doses of study treatments and flexible doses of permitted antihypertensive therapy
      (diuretics, beta blockers, alfa blockers, centrally acting adrenergic blockers. Blood
      pressure, blood glucose concentrations and urinary albumin excretion rate will be monitored
      every three months. Serum lipid concentrations and GFR (estimated with the iohexol plasma
      clearance) will be measured every six months.

      Primary and Secondary Variables. The primary efficacy variable of this study is the rate of
      GFR decline. The secondary efficacy variable will be the incidence of major cardiovascular
      events (acute myocardial infarction, ictus or stroke, heart failure requiring
      hospitalization, revascularization, amputation and cardiovascular mortality).
    

Intervention name(s): Delapril, Delapril-Manidipine Fixed combination
Intervention type(s): Drug
Intervention MeSH terms: Manidipine; Delapril
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Diagnostic