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

This study has been completed.
Sponsor:
Information provided by:
NicOx Research Institute S.r.l.
ClinicalTrials.gov Identifier:
NCT01256775
First received: December 6, 2010
Last updated: January 18, 2011
Last verified: January 2011
  Purpose

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.


Condition Intervention Phase
Intermittent Claudication
Drug: NCX-4016
Drug: NCX4016 placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Double-blind, Randomized, Parallel Group Study to Assess the Effect of NCX4016 vs Placebo on Walking Distance in Patients With Peripheral Arterial Occlusive Disease at Leriche-Fontaine Stage II

Resource links provided by NLM:


Further study details as provided by NicOx Research Institute S.r.l.:

Primary Outcome Measures:
  • maximal walking distance evaluated by a constant treadmill test [ Time Frame: baseline ] [ Designated as safety issue: No ]
  • maximal walking distance evaluated by a constant treadmill test [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • pain-free walking distance [ Time Frame: baseline, 1-3-6 months ] [ Designated as safety issue: No ]
  • assessment of carotid artery IMT [ Time Frame: baseline and 6 month ] [ Designated as safety issue: No ]

Enrollment: 442
Study Start Date: September 2003
Study Completion Date: April 2005
Primary Completion Date: April 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: NCX4016 placebo
NCX4016 placebo b.i.d for 6 months
Drug: NCX4016 placebo
NCX4016 placebo b.i.d. for 6 months
Active Comparator: NCX4016
ncx4016,800 mg b.i.d., on top of aspirin 100 mg o.d.
Drug: NCX-4016
NCX4016 800 mg b.i.d. for 6 months on top of aspirin 100 mg o.d.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01256775

Locations
Italy
Ospedale di Perugia
Perugia, Italy, 06126
Sponsors and Collaborators
NicOx Research Institute S.r.l.
Investigators
Principal Investigator: Paolo Gresele, M.D., Ph.D. University of Perugia, Italy
  More Information

No publications provided

Responsible Party: NicOx Research Institute, Paolo Gresele, University of Perugia - Italy
ClinicalTrials.gov Identifier: NCT01256775     History of Changes
Other Study ID Numbers: NCX4016-X-208
Study First Received: December 6, 2010
Last Updated: January 18, 2011
Health Authority: Italy: Ethics Committee

Keywords provided by NicOx Research Institute S.r.l.:
atherosclerosis
carotid intima-media thickness
intermittent claudication
Nitric Oxide / NO

Additional relevant MeSH terms:
Arterial Occlusive Diseases
Intermittent Claudication
Peripheral Arterial Disease
Vascular Diseases
Cardiovascular Diseases
Arteriosclerosis
Signs and Symptoms
Atherosclerosis
Peripheral Vascular Diseases
Nitroaspirin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cysteine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 23, 2014