Peripheral artery disease. Patients due for by-pass surgery of lower extremity arteries. MedDRA version: 12.0 Level: HLT Classification code 10034638 Term: Peripheral vascular disorders NEC MedDRA version: 12.0 Level: LLT Classification code 10003611 Term: Atherosclerosis of arteries of the extremities, unspecified
Conditions
Interventions
Trade Name: Atacand
Product Name: Atacand
Pharmaceutical Form: Tablet
INN or Proposed INN: CANDESARTAN CILEXETIL
CAS Number: 145040-37-5
Concentration unit: mg milligram(s)
Concentration type: up to
C
Sponsors
Wallenberg laboratory
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1/ Claudicatio intermittens 2/ Patients are considered suitable for reconstruction of the femoral artery using open surgical technique. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Patient already on treatment with angiotensin recepeptor blockade (ARB) and/or angiotensin converting enzyme inhibitor (ACEi). 2) Due to the medical condition - patient can not wait 5-8 weeks for surgical intervention. 3) Contra-indicated with angiotensin receptor blockers 4) Reduced renal function (estimated creatinine clearance < 60 ml/min/1.72m2). 5) Known renal artery stenosis 6) Known heart failure with ejection fraction (EF) <40 % 7) Informed consent can not be obtained since patient can not understand written or spoken Swedish.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Using pharmacological blockade of the angiotensin II receptor type 1, we aim to elucidate which molecular pathways mediate the pro-inflammatory and pro-angiogenc effects of angiotensin II. Using pharmacological blockade of the angiotensin II receptor type 1 (ARB), we aim to elucidate if ARB treatment can affect histological markesr of inflammation and angiogenesis.;Secondary Objective: Using pharmacological blockade of the angiotensin II receptor type 1 (ARB), we aim to elucidate if ARB treatment can affect serum markers of inflammation and angiogenesis.;Primary end point(s): Primary end-point 1) A coordinated regulatory pattern of gene regulation in plaque tissue indicating either an anti-inflammatory activity or an alteration in angiogenesis drive induced by angiotensin receptor blockers. a) To fulfill the criteria for a tissue anti-inflammatory activity the mRNA expression of one or more of the following pre-specified groups of candidate genes should be significantly altered in plaque tissue measured using immunohistochemistry; i/ reductions in 2 of 3 adhesion molecule (ICAM-1, VCAM-1 or e-selectin); ii/ reduction in 2 of 3 pro-inflammatory cytokines (TNF-alfa, IL-1 or MCP-1); iii/ increase in 2 anti-inflammatory cytokines TGF-alfa or IL-10. b) To fulfill the criteria for changes in angiogenesis signaling the mRNA expression of 3 of the following 5 candidate genes should be significantly altered in plaque tissue measured using immunohistochemistry; reductions in VEGF, VEGF-R2, FGF-2, FLT-1 or HGF. 2) A significant change in plaque tissue protein expression of histological markers of inflammation, angiogenesis and plaque stability. The following histological or immunohistochemical markers will be used; picro Sirius red, (collagen), smooth muscle actin, CD68, VEGF, VEGF-R2, HIF-1alfa. 3) Reduced level of serum markers of inflammation and angiogenesis. Serum markers that will be used includes: hsCRP, IL-6, s-VEGF, TNF-alfa and MCP-1. | — |
Countries
Sweden
Outcome results
None listed