VIRTUOSE : Efficiency of Sildenafil on the Absolute Claudication Distance of Peripheral Arterial Disease Patients With Intermittent Claudication.

Last updated: June 20, 2025
Sponsor: Rennes University Hospital
Overall Status: Active - Not Recruiting

Phase

3

Condition

Claudication

Peripheral Arterial Occlusive Disease

Peripheral Arterial Disease (Pad)

Treatment

Sildenafil

Placebo

Clinical Study ID

NCT03686306
VIRTUOSE
20 07 41
MEDAECNAT-2020-07- 00008
2020-000231-42
  • Ages > 18
  • All Genders

Study Summary

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 and was withdrawn as a therapy in 2010.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 Preliminary data from the literature and unpublished case reports, suggest that this drug could efficiently improve symptoms and walking capacity in patients with stage 2 claudication.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Patient ≥ 18 years old;

  2. with peripheral artery disease (ABI ≤ 0.90 or TBI ≤ 0.70 or post-exercise ABIdecrease 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

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 ofsildenafil

  • 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 failureand 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

  1. Pregnancy or breastfeeding;

  2. Subjects under reinforced protection, deprived of liberty by judicial oradministrative decision, hospitalized without consent or admitted to a health orsocial care establishment for purposes other than research;

  3. Being in an exclusion period for another clinical study or in an ongoinginterventional clinical study.

Study Design

Total Participants: 106
Treatment Group(s): 2
Primary Treatment: Sildenafil
Phase: 3
Study Start date:
November 24, 2021
Estimated Completion Date:
June 24, 2026

Study Description

Experimental design A Phase III, National, Multicentre, Prospective, Randomised, Double Blind, placebo-controlled clinical trial with two parallel groups.

Eligible patients will be randomised in two groups:

  • Experimental group Sildenafil citrate 140 mg/day (single morning oral dose of 140 mg) for a total duration of 24 weeks.

  • Control group Placebo (single morning oral dose) for a total duration of 24 weeks.

Treatment will be proposed in addition to optimal treatment (Antiplatelet / Direct Oral Anticoagulant + Lipid Lowering Drugs + AT2 antagonists / ACE Inhibitors; unless contra-indicated) + advice to walk.

The experimental drug will be delivered for a 4 weeks treatment period. Phone contact will be carried out at 7 and 14 days focusing on tolerance, compliance and eventual side effects.

First follow up visit at week 4 will focus on tolerance, compliance and side effects. If no major side effect is found, the study drug will be delivered for an additional 8 weeks.

Phone contact will be carried out at 8 weeks focusing on tolerance, compliance and eventual side effects.

Patients will be evaluated at week 12 (second follow-up visit) for persistent or non-persistent indication for revascularization and considered for revascularization if needed. In parallel, attention will be given to tolerance, compliance and eventual side effects. If no major side effect is found, the study drug will be delivered for an additional 12 weeks period.

Phone contact will be carried out at weeks 16 and 20 focusing on tolerance, compliance and eventual side effects.

Third and fourth follow-up visits are scheduled at week 24 (end of treatment) and week 48 (24 weeks after the end of experimental drugs).

Perspectives

  • Improving quality of life of patients suffering a chronic debilitating disease is a major issue not only in vascular medicine.

  • It is expected that the treatment may help patients change from a vicious circle (Pain > inactivity > disease progression > pain > increased morbi-mortality) to a virtuous circle (no Pain > improved ability for activity > collateral vessel development > slowing of disease progression > decreased morbi-mortality )

  • We expect that half of the patients that fulfil inclusion criteria will be sufficiently improved not to require surgery anymore even 24 weeks after the end of the drug as a result of this virtuous circle.

Connect with a study center

  • Guillaume MAHE

    Rennes, Bretagne 35033
    France

    Site Not Available

  • Rennes University Hospital

    Rennes, Bretagne 35033
    France

    Active - Recruiting

  • Amiens University Hospital

    Amiens,
    France

    Site Not Available

  • Bordeaux University Hospital

    Bordeaux,
    France

    Site Not Available

  • Caen University Hospital

    Caen,
    France

    Site Not Available

  • Cholet Hospital

    Cholet,
    France

    Site Not Available

  • Grenoble University Hospital

    Grenoble,
    France

    Site Not Available

  • Groupe Hospitalier Mutualiste de Grenoble

    Grenoble, 38000
    France

    Site Not Available

  • Mulhouse Hospital

    Mulhouse,
    France

    Site Not Available

  • Nîmes University Hospital

    Nîmes,
    France

    Site Not Available

  • AP-HP - Hôpital Européen Georges Pompidou

    Paris,
    France

    Site Not Available

  • Hospital Paris Saint-Joseph and Hospital Marie Lannelongue

    Paris,
    France

    Site Not Available

  • Saint-Etienne University Hospital

    Saint-Etienne,
    France

    Site Not Available

  • Toulouse University Hospital

    Toulouse,
    France

    Site Not Available

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