Effect of NCX4016 on Walking Distance in Patients With Peripheral Arterial Occlusive Disease (PAOD)

• Status: Completed
• Trial end date: 2005-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Peripheral arterial disease (PAD) is almost invariably associated with a generalized atherosclerotic involvement of the arterial tree and endothelial dysfunction. Previous short term studies showed improvement of vascular reactivity and walking capacity in PAD patients by measures aimed at restoring Nitric Oxide (NO) production. NO is also known to prevent the progression of atherosclerosis. We wished to assess whether the prolonged administration of a NO-donating agent (NCX 4016) improves the functional capacity of PAD patients and affects the progression of atherosclerosis as assessed by carotid intima-media thickness (IMT).

Four hundred forty two patients with stable intermittent claudication were enrolled in a prospective, double blind, placebo-controlled study and randomized to either NCX 4016 800mg bid or its placebo for 6 months. The primary study outcome was the absolute claudication distance (ACD) on a constant treadmill test (10% incline, 3km/hr); main secondary end-point was the change of the mean far-wall right common carotid artery IMT.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: NicOx Research Institute S.r.l.
• Treatments: Aspirin; Nitroaspirin

Criteria

Inclusion Criteria:

• male and female patients between 40 and 80 years with Leriche-Fontaine stage II PAD presenting symptoms of intermittent claudication stable for at least 6 months

• ankle/brachial index <0.9

• an absolute claudication distance (ACD) <500 m

• an initial claudication distance (ICD) >50 m on a standardized treadmill test (3% incline, 3 km/hr)

• and clinical stability before inclusion (i.e. changes in ACD not exceeding 25% in two standardized treadmill tests during run-in).

• all patients gave their written informed consent.

Exclusion Criteria:

• unstable symptoms and/or rapid deterioration of PAD during the previous 3 months

• presence of clinically significant renal or hepatic failure, or insulin-dependent type 1 diabetes

• uncontrolled type 2 diabetes, arterial hypertension or dyslipidemia

• any clinical condition limiting the patient's exercise ability (angina pectoris, congestive heart failure, respiratory disease, bone and joint disease, neurological disorders)

• active peptic ulcer during the previous 6 months

• any hemorrhagic condition or history of bleeding

• acute coronary syndrome or acute cerebrovascular episodes during the previous 6 months

• previous revascularization procedures during the last 6 months or indication for vascular surgery; ischemic rest pain

• life expectancy <12 months

• pregnancy or lactation

• participation to other investigational trials within 3 months prior to inclusion

• history of hypersensitivity or any form of allergic reaction or contraindications to NSAIDs, aspirin, and NO-donating drugs

• the following treatments were not allowed for the period of the study: continuative use (>7 days) of NSAIDs or nitrovasodilating drugs

• phosphodiesterase type 5 inhibitors, anticoagulants, heparin, ticlopidine, clopidogrel, indobufen, defibrotide, mesoglycan, picotamide, pentoxyfylline, carnitine, sulodexide

• All other concomitant treatments were kept constant as much as possible during the study period.