Efficacy of Sildenafil on the Morbi-mortality of Peripheral Arterial Diseased Patients With Intermittent Claudication (VALSTAR)

Efficacy of Sildenafil on the Morbi-mortality of Peripheral Arterial Diseased Patients With Intermittent Claudication. A 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 the most common clinical feature of PAD.

Primary therapeutic approach is medical treatment and advice to walk. Sildenafil, a PDEi type 5, 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.

For patients agreeing and signing informed consent, randomisation of treatment (placebo/sildenafil) will be done. Treatment will be proposed in addition to usual treatment. The experimental drug will be delivered for a 1 month treatment. First follow up visit at month one will focus on tolerance, compliance and eventual side effects. If no major side effect is found the study drug will then be delivered for an additional 2 months. Patients will be evaluated at month 3 (second follow-up visit) for persistent or non-persistent indication for revascularisation and addressed for revascularization if needed. In parallel focus on tolerance, compliance and eventual side effects will be done. If no major side effect is found, the study drug will be delivered for an additional 3 months treatment. Third and fourth follow-up visit are scheduled at month 6 (end of treatment) and month 9 (3 months after the end of experimental drugs).

Study Overview

• Status: Withdrawn
• Conditions: Peripheral Arterial Occlusive Disease
• Intervention / Treatment: Drug: Sildenafil 100 mg oral morning dose; Drug: Placebo oral morning dose

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Grade I cat 2 or 3 claudication despite optimal medical treatment
• Reporting a vascular claudication history for at least 3 months
• Able to achieve a walking treadmill test, Walking time on treadmill (3.2km/h, 10% slope) less than 5 minutes
• Having no cons Sildenafil indication
• Must be on optimal medical therapy (ACE Inhibitors / AT2 Antagonist + Antiplatelet + Lipid Lowering drugs) for at least 1 month

Exclusion Criteria:

• Critical ischemia
• Previous history of myocardial infarction or angina not stabilized
• Amblyopia
• Treated with nitrates (nitroglycerin ...) or drugs interfering with the action of the Sildenafil
• Pregnant woman and woman in labor
• Major Person subject to reinforced protection, deprived of their liberty by judicial or administrative decision, hospitalized without consent or admitted to a health or social establishment for purposes other than research
• Being in an exclusion period for another biomedical study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sildenafil; Single Sildenafil oral morning intake (100mg/day) per day for a total duration of 6 months (Sildenafil 100 mg oral morning dose)	Drug: Sildenafil 100 mg oral morning dose; Measurement of maximal walking distance on a constant load treadmill test, SF-36 questionnaire, and Edimburg questionnaire at inclusion, 1 month, 3 month and 6 month. Events occurence questionnaires, Tolerance and adverse events questionnaire, Welch questionnaire and walk recommendation at inclusion, 7 days, 14 days, 1-2-3-4-5-6 and 9 months; Other Names: Experimental: Sildenafil
Placebo Comparator: Placebo; Single Placebo oral morning intake per day for a total duration of 6 months (Placebo oral morning dose)	Drug: Placebo oral morning dose; Measurement of maximal walking distance on a constant load treadmill test, SF-36 questionnaire, and Edimburg questionnaire at inclusion, 1 month, 3 month and 6 month. Events occurence questionnaires, Tolerance and adverse events questionnaire, Welch questionnaire and walk recommendation at inclusion, 7 days, 14 days, 1-2-3-4-5-6 and 9 months; Other Names: Placebo Comparator: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of Event free survival rate	Event free survival is defined as the time between inclusion date and the date of event occurrence. If no event is observed at the follow-up period, event free survival is defined as the delay of follow-up	6 months after the treatment begining

Collaborators and Investigators

• Sponsor: University Hospital, Angers
• Investigators: Study Director: Loukman OMARJEE, MD, University Hospital, Angers

Publications and helpful links

General Publications

• Omarjee L, Camarzana A, Henni S, Abraham P. Nonrevascularizable buttock claudication improved with Sildenafil: A case report. Medicine (Baltimore). 2017 Feb;96(8):e6186. doi: 10.1097/MD.0000000000006186.

Study record dates

Study Major Dates

• Primary Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: October 10, 2016
• First Submitted That Met QC Criteria: October 10, 2016
• First Posted (Estimate): October 12, 2016

Study Record Updates

• Last Update Posted (Actual): November 6, 2018
• Last Update Submitted That Met QC Criteria: November 2, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Intermittent Claudication; Arterial Occlusive Diseases; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: PHRC-N-2015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No