VIRTUOSE : Efficiency of Sildenafil on the Absolute Claudication Distance of Peripheral Arterial Disease Patients With Intermittent Claudication.
Keywords
Abstract
Description
Experimental design A 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 100 mg/day (single morning oral dose of 100 mg) + advice to walk for a total duration of 6 months.
- Control group Placebo (single morning oral dose) + 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 . The experimental drug will be delivered for a 1 month treatment period. Phone/mail contact will be carried out at 7 and 14 days focusing on tolerance, compliance and eventual side effects. First follow up visit at month one will focus on tolerance, compliance and side effects and walking capacity . If no major side effect is found, the study drug will be delivered for an additional 2 months. Phone/mail contact will be carried out at 2 months focusing on tolerance, compliance and eventual side effects. Patients will be evaluated at month 3 (second follow-up visit) for persistent or non-persistent indication for revascularisation and considered for revascularisation 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 3 months period. Phone/mail contact will be carried out at 4 months and 5 months focusing on tolerance, compliance and eventual side effects Third and fourth follow-up visits are scheduled at month 6 (end of treatment) and month 12 (6 months 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 3 months after the end of the drug as a result of this virtuous circle.
Dates
| Last Verified: | 10/31/2019 |
| First Submitted: | 09/23/2018 |
| Estimated Enrollment Submitted: | 09/24/2018 |
| First Posted: | 09/25/2018 |
| Last Update Submitted: | 11/04/2019 |
| Last Update Posted: | 11/05/2019 |
| Actual Study Start Date: | 02/29/2020 |
| Estimated Primary Completion Date: | 02/28/2022 |
| Estimated Study Completion Date: | 02/28/2023 |
Condition or disease
Intervention/treatment
Drug: Experimental group
Drug: Control group
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: Experimental group Sildenafil 100 mg/day (single morning oral dose of 100 mg) + advice to walk for a total duration of 6 months. | Drug: Experimental group Sildenafil 100 mg/day (single morning oral dose of 100 mg) + 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. |
| Placebo Comparator: Control group Placebo (single morning oral dose) + advice to walk for a total duration of 6 months. | Drug: Control group Placebo (single morning oral dose) + 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. |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: - Patient ≥ 18 years old; - with peripheral artery disease (ABI < 0.90) reporting stable limiting claudication despite optimal medical treatment (Antiplatelet + Lipid Lowering Drugs + AT2 antagonists / ACE Inhibitors; unless contra-indication) and advise to walk for at least one month; - with a walking capacity between 200 and 500 meters on treadmill; - affiliation to a social security agency - Patient who has understood the protocol and signed the consent form to participate. Exclusion Criteria: - Revascularisation already decided and scheduled; - Critical limb ischemia; - Life threatening disease; - Contraindication related to Sildenafil : - Recent history of myocardial infarction or stroke - Unstable angina - Hypotension (Blood pressure < 90/50 mmHg) - Patients treated with nitrates or drugs interfering with the action of sildenafil - Severe renal or hepatic failure - Amblyopia - Loss of vision in one eye because of NAION - Known hereditary degenerative retinal disorders such as retinitis pigmentosa - Pregnancy; - 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 biomedical study. |
Outcome
Primary Outcome Measures
1. Absolute claudication distance [baseline and month 6]
Secondary Outcome Measures
1. surgical re-vascularisation [baseline and month 12]
2. ACD [baseline and month 12]
3. Event free survival (EFS) [Through the study completion, an average of 1 year]
4. 36-Item Short Form Health Survey (SF36) [baseline and months 3, 6 and 12]
5. Peripheral Artery Questionnaire [baseline and months 3, 6 and 12]
6. oxymetry [baseline and month 6]
7. Endothelial function by Laser Speckle [month 6 and month 12]
8. respect of prescribed dose [Through the study completion, an average of 1 year]
9. adverse events [Through the study completion, an average of 1 year]
