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

NCT03686306 | Active Not Recruiting Phase 3

• 4 other identifiers: VIRTUOSE2020-000231-4220 07 41MEDAECNAT-2020-07- 00008
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 11

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 and was withdrawn as a therapy in 2010.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 Preliminary data from the literature and unpublished case reports, suggest that this drug could efficiently improve symptoms and walking capacity in patients with stage 2 claudication.

Conditions

Peripheral Artery Disease

Outcome Measures

Primary Outcomes (1)

• Absolute claudication distance

  Absolute change of the absolute claudication distance (ACD) from baseline to week 24

  Baseline and week 24

Secondary Outcomes (15)

• Surgical re-vascularisation

  baseline and weeks 24 and 48

• ACD

  Baseline and week 48

• Event free survival (EFS)

  Through the study completion, an average of 1 year

• 36-Item Short Form Health Survey (SF36)

  Baseline and weeks 12, 24 and 48

• Peripheral Artery Questionnaire

  Baseline and weeks 12, 24 and 48

Study Arms (2)

Experimental group

EXPERIMENTAL

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

Drug: Sildenafil

Control group

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Sildenafil DRUG

Sildenafil citrate 140 mg/day (single morning oral dose of 140 mg) for a total duration of 24 weeks. + advice to walk for a total duration of 6 months. Treatment will be proposed in addition to optimal treatment (Antiplatelet + Lipid Lowering Drugs + AT2 antagonists / ACE Inhibitors; unless contra-indicated) + advice to walk.

Experimental group

Placebo DRUG

Placebo (single morning oral dose) + advice to walk 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.

Control group

Eligibility Criteria

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

You may qualify if:

• Patient ≥ 18 years old;
• 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;
• with a walking capacity lower or equal to 500 meters on treadmill;
• affiliation to a social security agency
• Patient who has understood the protocol and signed the consent form to participate.

You may not qualify if:

• Revascularization already decided and scheduled;
• Critical limb ischemia;
• Life threatening disease;
• 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

Sponsors & Collaborators

• Rennes University Hospital: lead

Study Sites (11)

Guillaume MAHE

Rennes, Brittany Region, 35033, France

Location

Amiens University Hospital

Amiens, France

Location

Bordeaux University Hospital

Bordeaux, France

Location

Caen University Hospital

Caen, France

Location

Cholet Hospital

Cholet, France

Location

Groupe Hospitalier Mutualiste de Grenoble

Grenoble, 38000, France

Location

Grenoble University Hospital

Grenoble, France

Location

Mulhouse Hospital

Mulhouse, France

Location

Nîmes University Hospital

Nîmes, France

Location

AP-HP - Hôpital Européen Georges Pompidou

Paris, France

Location

Hospital Paris Saint-Joseph and Hospital Marie Lannelongue

Paris, France

Location

MeSH Terms

Conditions

Peripheral Arterial Disease

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The preparation of the 'blinded' treatments will be undertaken by the PPRIGO hospital pharmacist's consortium (Production Pharmaceutique pour la Recherche Institutionnelle du Grand Ouest) under recommended standardised conditions. PPRIGO will provide numbered and labelled boxes each containing 32 capsules of the study drug (sildenafil or placebo according to the randomisation order). All boxes will be identically labelled, with the study number being the only differentiating feature between different drug packs. The un-blinding will be centralised with eCRF software in agreement with the principal investigator.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: September 24, 2018
• First Posted: September 26, 2018
• Study Start: November 24, 2021
• Primary Completion: November 24, 2025
• Study Completion (Estimated): June 24, 2026
• Last Updated: June 24, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (11)