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

NCT01256775 | Completed Phase 2 DMC

• 1 other identifier: NCX4016-X-208
• Study Type: interventional
• Target: 442
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Intermittent Claudication

Keywords

atherosclerosis; carotid intima-media thickness; intermittent claudication; Nitric Oxide / NO

Outcome Measures

Primary Outcomes (2)

• maximal walking distance evaluated by a constant treadmill test

  baseline

• maximal walking distance evaluated by a constant treadmill test

  6 months

Secondary Outcomes (2)

• pain-free walking distance

  baseline, 1-3-6 months

• assessment of carotid artery IMT

  baseline and 6 month

Study Arms (2)

NCX4016 placebo

PLACEBO COMPARATOR

NCX4016 placebo b.i.d for 6 months

Drug: NCX4016 placebo

NCX4016

ACTIVE COMPARATOR

ncx4016,800 mg b.i.d., on top of aspirin 100 mg o.d.

Drug: NCX-4016

Interventions

NCX-4016 DRUG

NCX4016 800 mg b.i.d. for 6 months on top of aspirin 100 mg o.d.

NCX4016

NCX4016 placebo DRUG

NCX4016 placebo b.i.d. for 6 months

NCX4016 placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• all patients gave their written informed consent.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• NicOx Research Institute S.r.l.: lead

Study Sites (1)

Ospedale di Perugia

Perugia, Italy, 06126, Italy

Location

MeSH Terms

Conditions

Intermittent Claudication; Atherosclerosis

Interventions

nitroaspirin

Condition Hierarchy (Ancestors)

Peripheral Arterial Disease; Peripheral Vascular Diseases; Vascular Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Arteriosclerosis; Arterial Occlusive Diseases

Study Officials

• Paolo Gresele, M.D., Ph.D.

  University Of Perugia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: December 6, 2010
• First Posted: December 9, 2010
• Study Start: September 1, 2003
• Primary Completion: April 1, 2005
• Study Completion: April 1, 2005
• Last Updated: January 19, 2011

Record last verified: 2011-01

Locations

IT (1)