VIRTUOSE: Efficiency of sildenafil on the absolute claudication distance of peripheral arterial disease patients with intermittent claudication. A phase III, National, Multicenter, Prospective, Randomized, Double-blind, Placebo-Controlled trial.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Rennes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14], Phenomena and Processes [G] - Circulatory and Respiratory Physiological Phenomena [G09], Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

24 Nov 2021 → 6 Oct 2025

Decision date (initial)

2024-10-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS

External identifiers

EU CT number

2024-516429-30-00

EudraCT number

2020-000231-42

ClinicalTrials.gov

NCT03686306

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To determine whether sildenafil, compared with placebo, improve the walking capacity at week 24 of patients with intermittent claudication

Secondary objectives 12

1. To determine whether sildenafil, compared with placebo, from baseline, prevents surgical revascularization procedure at weeks 24 and 48
2. To determine whether sildenafil, compared with placebo, from baseline, improves the walking capacity at week 48
3. To determine whether sildenafil, compared with placebo, from baseline, improves the time to first event. 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.
4. To determine whether sildenafil, compared with placebo, from baseline, improves the quality of life at weeks 12, 24 and 48.
5. To determine whether sildenafil, compared with placebo, from baseline, improves the exercise oximetry results at weeks 12, 24 and 48.
6. To determine whether sildenafil, compared with placebo, from baseline, improves endothelial function at weeks 12, 24 and 48.
7. To determine whether sildenafil, compared with placebo, from baseline, improves pulmonary function and diffusion capacity of the lungs for carbon monoxide (DLCO) at week 24.
8. To determine whether sildenafil, compared with placebo, from baseline, improves arterial stiffness (Pulse Wave Velocity) and Central Blood Pressure with pOpmetre® at weeks 12, 24 and 48.
9. To determine whether sildenafil, compared with placebo, from baseline, improves arterial compliance and vascular resistance with Finometer® at weeks 12, 24 and 48.
10. To determine whether sildenafil, compared with placebo, from baseline, changes metabolomic signature and biological parameters between baseline and week 24.
11. To evaluate compliance with the treatment
12. To evaluate tolerance and perceived symptoms.

Conditions and MedDRA coding

Peripheral arterial disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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 mm Hg) 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 7

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Absolute change of the absolute claudication distance (ACD) from baseline to week 24. ACD is measured in meters at baseline and week 24 by walking on a treadmill until the point when the subject is unable to walk anymore due to pain in the leg. For the treadmill tests, walking will be conducted up to the maximum walking ability (not only the appearance of a pain) or to a maximum of 15 minutes.

Secondary endpoints 12

1. Rate of patients with surgical revascularization at weeks 24 and 48
2. Absolute change of the ACD from baseline to week 48: For the treadmill tests, walking will be conducted up to the maximum walking ability (not only the appearance of a pain) or to a maximum of 15 minutes.
3. Event free survival (EFS) from baseline until week 48: 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
4. SF36 questionnaire and Peripheral Artery Questionnaire at baseline, weeks 12, 24 and 48
5. Change in exercise oximetry results between baseline and weeks 12, 24 and 48
6. Change in endothelial function between baseline and weeks 12, 24 and 48
7. Changes in pulmonary function and diffusion capacity of the lungs for carbon monoxide (DLCO) at week 24 from baseline
8. Changes in arterial stiffness (Pulse Wave Velocity) and Central Blood Pressure with pOpmetre® between baseline and weeks 12, 24 and 4
9. Changes in arterial compliance and vascular resistance with Finometer® between baseline and weeks 12, 24 and 48
10. Change in metabolomics signature between baseline and week 24
11. Compliance with the treatment
12. Tolerance and perceived symptoms

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Rennes

Sponsor organisation

Centre Hospitalier Universitaire De Rennes

Address

2 Rue Henri Le Guilloux

City

Rennes

Postcode

35000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Rennes

Contact name

Dr Loukman OMARJEE

Public contact point

Organisation

Centre Hospitalier Universitaire De Rennes

Contact name

Violaine BENOIT

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications