Ignite Creation Date:
2024-05-05 @ 11:06 PM
Last Modification Date:
2024-10-26 @ 10:28 AM
Study NCT ID:
NCT01256775
Status:
COMPLETED
Last Update Posted:
2011-01-19
First Post:
2010-12-06
Brief Title:
Effect of NCX4016 on Walking Distance in Patients With Peripheral Arterial Occlusive Disease PAOD
Sponsor:
NicOx Research Institute Srl
Organization:
NicOx Research Institute Srl
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2011-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 3kmhr main secondary end-point was the change of the mean far-wall right common carotid artery 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 3kmhr main secondary end-point was the change of the mean far-wall right common carotid artery IMT
Detailed Description:
Design of the study This was a prospective randomized double-blind parallel-groups placebo-controlled study conducted in fortythree clinical sites throughout Europe 442 patients with peripheral arterial occlusive disease PAD at Leriche-Fontaine stage II were treated with NCX 4016 800 mg bid or with an indistinguishable placebo for 6 months The dosage of 800 mg bid was selected based on previous clinical studies which demonstrated a good safety profile and a good tolerability in the gastro intestinal tract Compliance was checked by counting dispensed versus returned study medication
All patients received 100 mg aspirin once daily for cardiovascular prevention standard for this patient population at the time of study design
Inclusion criteria were 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 an anklebrachial index 09 an absolute claudication distance ACD 500 m and an initial claudication distance ICD 50 m on a standardized treadmill test 3 incline 3 kmhr and clinical stability before inclusion ie changes in ACD not exceeding 25 in two standardized treadmill tests during run-in All patients gave their written informed consent
Exclusion criteria were unstable symptoms andor 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 patients 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
Primary end-point of the study was the ACD on a constant treadmill test secondary end-points were ICD responder rates ie the proportion of patients showing a 28 or a 50 improvement of ACD in comparison with baseline quality of life questionnaire Short-Form 36 SF-36 the variations of the anklebrachial index ABI between baseline and 6 months and the modifications of the intimal medial thickness IMT of the common right carotid artery at 6 months as compared with baseline
Common right carotid artery was examined by B-mode ultrasound in the longitudinal view 1-15 cm proximally to the bifurcation The measurement of IMT was obtained according to the Mannheim carotid intima-media thickness consensus with one modification instead of acquiring the vascular wall image only with the lateral probe incidence images were acquired also with the anterior and posterior incidence in order to obtain a triplicate number of measurements to be used for comparisons Each position was visualized and recorded for at least 15 sec with simultaneous taking of the ECG tracing Images of the far wall of the distal 1 cm of the right common carotid artery were obtained IMT was calculated from each of the three projections and the final value was calculated from the average of all measurements with the use of standardized ultrasonography settings The baseline carotid ultrasonographic examinations were used to localize the site of interest at follow-up Digitized still images from an electrocardiographically defined diastolic frame were analyzed offline A single observer who was unaware of the treatment assignments and the identities of the patients measured the mean carotid intima media thickness Focal atherosclerotic plaques were excluded from the measurements All measurements were performed with the use of an automated border detection system A number of measurements not inferior to 30 for each of the three image acquisition incidences was carried out in the 1cm segment of the carotid artery assessed For each subject the same ultrasound system and transducer and the same operator were used throughout the study Images were centrally analyzed at the coordinating center by a dedicated automated computerized edge detection system for the measurement of common carotid far wall intima-media using the software MATH 20 Metris Argenteuil France
All patients received 100 mg aspirin once daily for cardiovascular prevention standard for this patient population at the time of study design
Inclusion criteria were 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 an anklebrachial index 09 an absolute claudication distance ACD 500 m and an initial claudication distance ICD 50 m on a standardized treadmill test 3 incline 3 kmhr and clinical stability before inclusion ie changes in ACD not exceeding 25 in two standardized treadmill tests during run-in All patients gave their written informed consent
Exclusion criteria were unstable symptoms andor 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 patients 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
Primary end-point of the study was the ACD on a constant treadmill test secondary end-points were ICD responder rates ie the proportion of patients showing a 28 or a 50 improvement of ACD in comparison with baseline quality of life questionnaire Short-Form 36 SF-36 the variations of the anklebrachial index ABI between baseline and 6 months and the modifications of the intimal medial thickness IMT of the common right carotid artery at 6 months as compared with baseline
Common right carotid artery was examined by B-mode ultrasound in the longitudinal view 1-15 cm proximally to the bifurcation The measurement of IMT was obtained according to the Mannheim carotid intima-media thickness consensus with one modification instead of acquiring the vascular wall image only with the lateral probe incidence images were acquired also with the anterior and posterior incidence in order to obtain a triplicate number of measurements to be used for comparisons Each position was visualized and recorded for at least 15 sec with simultaneous taking of the ECG tracing Images of the far wall of the distal 1 cm of the right common carotid artery were obtained IMT was calculated from each of the three projections and the final value was calculated from the average of all measurements with the use of standardized ultrasonography settings The baseline carotid ultrasonographic examinations were used to localize the site of interest at follow-up Digitized still images from an electrocardiographically defined diastolic frame were analyzed offline A single observer who was unaware of the treatment assignments and the identities of the patients measured the mean carotid intima media thickness Focal atherosclerotic plaques were excluded from the measurements All measurements were performed with the use of an automated border detection system A number of measurements not inferior to 30 for each of the three image acquisition incidences was carried out in the 1cm segment of the carotid artery assessed For each subject the same ultrasound system and transducer and the same operator were used throughout the study Images were centrally analyzed at the coordinating center by a dedicated automated computerized edge detection system for the measurement of common carotid far wall intima-media using the software MATH 20 Metris Argenteuil France
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None