Peripheral Artery DiseasePhase 3VIRTUOSENCT03686306
VIRTUOSE : Efficiency of Sildenafil on the Absolute Claudication Distance of Peripheral Arterial Disease Patients With Intermittent Claudication.
A Phase 3 study testing Sildenafil in people with Peripheral Artery Disease, run by Rennes University Hospital at 11 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Peripheral Artery Disease
- What is being tested?
- Sildenafil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 106 participants
- Where
- 11 sitesFrance
- Study dates
- 24 Nov 2021to 24 Jun 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 18Show fewer
- 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
- Pregnancy or breastfeeding;
- 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;
- Being in an exclusion period for another clinical study or in an ongoing interventional clinical study.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
France11 sites
Amiens University Hospital
Amiens
Bordeaux University Hospital
Bordeaux
Caen University Hospital
Caen
Cholet Hospital
Cholet
Groupe Hospitalier Mutualiste de Grenoble
Grenoble, 38000
Grenoble University Hospital
Grenoble
Mulhouse Hospital
Mulhouse
Nîmes University Hospital
Nîmes
AP-HP - Hôpital Européen Georges Pompidou
Paris
Hospital Paris Saint-Joseph and Hospital Marie Lannelongue
Paris
Guillaume MAHE
Rennes, Brittany Region, 35033
About this study
Official title: 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.
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.
Read more
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.
Read the detailed 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.
- Conditions
- Peripheral Artery Disease
- Being tested
- Sildenafil, Placebo
- Medical subject headings
- Peripheral Arterial Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Experimental | Sildenafil citrate 140 mg/day (single morning oral dose of 140 mg) for a total duration of 24 weeks. Receives: Drug: Sildenafil |
| Control group | Placebo comparator | Placebo (single morning oral dose) for a total duration of 24 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute claudication distance
Absolute change of the absolute claudication distance (ACD) from baseline to week 24
Measured: Baseline and week 24
Secondary outcomes (15)
Surgical re-vascularisation
Rate of patients with surgical re-vascularisation at weeks 24 and 48
Measured: baseline and weeks 24 and 48
ACD
Absolute change of the ACD from baseline to week 48
Measured: Baseline and week 48
Event free survival (EFS)
An "EVENT" is defined as either (1) major adverse cardiovascular events (MACE; including vascular deaths, non-fatal myocardial infarction and non-fatal stroke), (2) leg amputations, (3) Non Cardiovascular death.
Event-free survival is defined as the time from inclusion to the first documented event. If no event is observed, event-free survival is defined as the delay of follow-up.
Measured: Through the study completion, an average of 1 year
36-Item Short Form Health Survey (SF36)
Quality of life : SF36 questionnaire at baseline and weeks 12, 24 and 48
Measured: Baseline and weeks 12, 24 and 48
Peripheral Artery Questionnaire
Peripheral Artery Questionnaire at baseline and weeks 12, 24 and 48
Measured: Baseline and weeks 12, 24 and 48
Oxymetry
Change in exercise oxymetry results between baseline and weeks 12, 24 and 48
Measured: Baseline and weeks 12, 24 and 48
Endothelial function by Laser Speckle
Change in endothelial function at weeks 12, 24 and 48
Measured: Baseline and weeks 12, 24 and 48
Pulmonary function
Pulmonary function and diffusion capacity of the lungs for carbon monoxide (DLCO) at week 24 from baseline
Measured: Baseline and week 24
Respect of prescribed dose
Compliance with the treatment
Measured: Through the study completion, an average of 1 year
Tolerance
Tolerance and side effects
Measured: Through the study completion, an average of 1 year
Arterial stifness
Changes in arterial stiffness (Pulse Wave Velocity) with pOpmetre® between baseline and weeks 12, 24 and 48
Measured: Baseline and weeks 12, 24 and 48
Central Blood Pressure
Changes in Central Blood Pressure with pOpmetre® between baseline and weeks 12, 24 and 48
Measured: Baseline and weeks 12, 24 and 48
Arterial compliance
Changes in arterial compliance with Finometer® between baseline and weeks 12, 24 and 48
Measured: Baseline and weeks 12, 24 and 48
Vascular resistance
Changes in vascular resistance with Finometer® between baseline and weeks 12, 24 and 48
Measured: Baseline and weeks 12, 24 and 48
Metabolomics signature
Change in metabolomics signature between baseline and week 24
Measured: Baseline and week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2018
- Study start24 Nov 2021
- Primary completion24 Nov 2025 (estimated)
- Study completion24 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Peripheral Artery DiseaseStudies of the same condition, open and under way.
- More trials run by Rennes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Experimental design A Phase III, National, Multicentre, Prospective, Randomised, Double Blind, placebo-controlled clinical trial with two parallel groups.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03686306
- Sponsor's protocol ID
- VIRTUOSE
- Other IDs
- 2020-000231-42, 20 07 41, MEDAECNAT-2020-07- 00008
- Acronym
- VIRTUOSE
- Status last verified
- Jun 2025
- First submitted
- 24 Sep 2018
- Last updated
- 24 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT03686306
- Acronym / sponsor ID
- VIRTUOSE / VIRTUOSE
- Conditions
- Peripheral Artery Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 106 participants (actual)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Study start
- 24 Nov 2021 (actual)
- Primary completion
- 24 Nov 2025 (estimated)
- Study completion
- 24 Jun 2026 (estimated)
- First posted
- 26 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Experimental design A Phase III, National, Multicentre, Prospective, Randomised, Double Blind, placebo-controlled clinical trial with two parallel groups.
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Drug: SildenafilSildenafil citrate 140 mg/day (single morning oral dose of 140 mg) for a total duration of 24 weeks. |
| Control group | Placebo comparator | Drug: PlaceboPlacebo (single morning oral dose) for a total duration of 24 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (18 listed)
- Revascularization already decided and scheduled;
- Critical limb ischemia;
- Life threatening disease;
- Contraindication related to Sildenafil:
- Pregnancy or breastfeeding;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SildenafilSildenafil 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. | Drug | Experimental group |
| PlaceboPlacebo (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. | Drug | Control group |
Primary outcome
Absolute claudication distance
Time frame: Baseline and week 24
Absolute change of the absolute claudication distance (ACD) from baseline to week 24
15 secondary outcomes
Surgical re-vascularisation
Time frame: baseline and weeks 24 and 48
ACD
Time frame: Baseline and week 48
Event free survival (EFS)
Time frame: Through the study completion, an average of 1 year
36-Item Short Form Health Survey (SF36)
Time frame: Baseline and weeks 12, 24 and 48
Peripheral Artery Questionnaire
Time frame: Baseline and weeks 12, 24 and 48
Oxymetry
Time frame: Baseline and weeks 12, 24 and 48
Endothelial function by Laser Speckle
Time frame: Baseline and weeks 12, 24 and 48
Pulmonary function
Time frame: Baseline and week 24
Respect of prescribed dose
Time frame: Through the study completion, an average of 1 year
Tolerance
Time frame: Through the study completion, an average of 1 year
Arterial stifness
Time frame: Baseline and weeks 12, 24 and 48
Central Blood Pressure
Time frame: Baseline and weeks 12, 24 and 48
Arterial compliance
Time frame: Baseline and weeks 12, 24 and 48
Vascular resistance
Time frame: Baseline and weeks 12, 24 and 48
Metabolomics signature
Time frame: Baseline and week 24
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sildenafil in people with Peripheral Artery Disease, run by Rennes University Hospital at 11 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 24 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Absolute claudication distance (time frame: Baseline and week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2025; AzTrials last refreshed its copy on 7 Nov 2026.