VIRTUOSE : Efficiency of Sildenafil on the Absolute Claudication Distance of Peripheral Arterial Disease Patients With Intermittent Claudication. A Phase III, National, Multicentre, Prospective, Randomised, Double-blind, Placebo-Controlled Trial.

VIRTUOSE

Peripheral Arterial Disease (PAD) is a highly debilitating disease that affects 202 million people around the world and about 7 million people in France. Morbi-mortality from cardiovascular events is increased in this population. Intermittent claudication is defined as a discomfort and/or pain in the legs during walking. It is the most common clinical feature of PAD. In claudication, primary therapeutic approach is medical treatment and advice to walk. Revascularization is only proposed when medical treatment and advice to walk for at least 3 to 6 months have failed to improve symptoms and walking ability. Optimal medical treatment includes Antiplatelet, Lipid Lowering Drugs, AT2 antagonists / ACE Inhibitors and advice to walk. To date, no other drug has provided consistent evidence for functional improvement in claudication, except for Cilostazol, a type-3 phospho-diesterase inhibitor (PDEi). This compound has been scarcely used in France due to cost and frequent side effect (Headache, Flush, Diarrhea, etc.) and was withdrawn as a therapy in 2010. Sildenafil, a type 5 PDEi, is well tolerated, largely used in impotence and has interesting clinical delay and duration of action in the concept of a potential use in claudication. Preliminary data from the literature and unpublished case reports, suggest that this drug could efficiently improve symptoms and walking capacity in patients with stage 2 claudication.

2021-11-24

2024-11-24

2025-06-24

Recruiting

Early phase I

220

Inclusion Criteria: 1. Patient ≥ 18 years old; 2. with peripheral artery disease (ABI ≤ 0.90 or TBI ≤ 0.70 or post-exercise ABI decrease of 18.5% from rest or ABI Exercise TcPO2 with DROPmin ≤ - 15 mmHg) reporting stable limiting claudication despite optimal medical treatment (Antiplatelet / Direct Oral Anticoagulant + Lipid Lowering Drugs + AT2 antagonists / ACE Inhibitors; unless contra-indication) and advice to walk for at least 4 weeks; 3. with a walking capacity lower or equal to 500 meters on treadmill; 4. affiliation to a social security agency 5. Patient who has understood the protocol and signed the consent form to participate. Exclusion Criteria: 1. Revascularization already decided and scheduled; 2. Critical limb ischemia; 3. Life threatening disease; 4. Contraindication related to Sildenafil: * Patients treated with nitrates or drugs interfering with the action of sildenafil * Ongoing treatment by Ritonavir or alpha-blockers * Hypersensitivity to sildenafil or any of the excipients (lactose monohydrate) * Recent history of myocardial infarction or stroke \< 3 months * Severe cardiovascular disorders such as unstable angina, severe cardiac failure and cardiomyopathy * Hypotension (Blood pressure \< 90/50 mmHg) * Severe renal or hepatic failure * Amblyopia * Loss of vision in one eye because of Non-arterial ischemic Ophtalmic Neuropathy (NAION) * Known hereditary degenerative retinal disorders such as retinitis pigmentosa * Leukemia, Drepanocytosis, Multiple Myeloma 5. Pregnancy or breastfeeding; 6. Subjects under reinforced protection, deprived of liberty by judicial or administrative decision, hospitalized without consent or admitted to a health or social care establishment for purposes other than research; 7. Being in an exclusion period for another clinical study or in an ongoing interventional clinical study.

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2023-11-22