1. Effects of sildenafil on maximum walking time in patients with arterial claudication: The ARTERIOFIL study
- Author
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Valérie Daniel, Yoanna Onillon, Chadi Homedan, Pascal Reynier, Clara Locher, Loukman Omarjee, Juan-Manuel Chao de la Barca, Isabelle Laporte, Pierre Abraham, Jean-Marie Chretien, Manuela Ripoche, Vincent Jaquinandi, Alain Renault, Vincent Azzola, Marc-Antoine Custaud, Cedric Fontaine, Estelle Le Pabic, Céline Barbeau-Terrier, Guillaume Mahé, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier de Redon (CH Redon), Centre Hospitalier de Cholet, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Angers University Hospital, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), and Jonchère, Laurent
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0301 basic medicine ,Male ,Time Factors ,Physiology ,[SDV]Life Sciences [q-bio] ,Walking ,030204 cardiovascular system & hematology ,chemistry.chemical_compound ,0302 clinical medicine ,Clinical endpoint ,Medicine ,Prospective Studies ,Treadmill ,ComputingMilieux_MISCELLANEOUS ,Cross-Over Studies ,Exercise Tolerance ,Absolute walking time ,Middle Aged ,3. Good health ,Walking time ,[SDV] Life Sciences [q-bio] ,Treatment Outcome ,Anesthesia ,Molecular Medicine ,Exercise oximetry ,Female ,France ,medicine.symptom ,Sildenafil ,Treadmill walking test ,Walk Test ,Placebo ,Sildenafil Citrate ,03 medical and health sciences ,Peripheral Arterial Disease ,Double-Blind Method ,Humans ,Aged ,Pharmacology ,Peripheral artery disease ,business.industry ,Oxygenation ,Recovery of Function ,Intermittent Claudication ,Phosphodiesterase 5 Inhibitors ,respiratory tract diseases ,Clinical trial ,030104 developmental biology ,chemistry ,Claudication ,business ,Biomarkers - Abstract
Patients with lower extremity peripheral artery disease (PAD) frequently experience claudication, a clinical symptom indicative of reduced walking capacity. Recommended care consists of exercise rehabilitation combined with optimal medical treatment and surgery. The effects of a single oral dose of sildenafil, a phosphodiesterase type-5 inhibitor, on patients with claudication are discussed. The aim of this study was to test the efficacy of a single 100 mg dose of sildenafil compared to placebo in terms of maximal walking time (MWT) in patients with claudication.The ARTERIOFIL study is a crossover, double-blind, prospective, randomized, single-center study conducted at Angers University Hospital in France. MWT (primary endpoint) was assessed using a treadmill test (10% incline; 3.2 km/h). Secondary endpoints (pain-free walking time (PFWT), transcutaneous oximetry during exercise and redox cycle parameters and safety) were also studied.Fourteen patients were included of whom two were ultimately excluded. In the 12 remaining patients, the MWT was significantly improved during the sildenafil period compared with the placebo period (300 s [95% CI 172 s-428 s] vs 402 s [95% CI 274 s-529 s] p 0.01). Sildenafil had no significant effect on pain-free walking time or skin tissue oxygenation during exercise. According to redox cycle parameters, sildenafil significantly reduced blood glucose and pyruvate levels and the 3-hydroxybutyrate/acetoacetate ratio, while there was no significant effect on lactate, 3-hydroxybutyrate, acetoacetate and free fatty acid levels. Symptomatic transient hypotension was observed in two women.The ARTERIOFIL study has shown that a single 100 mg oral dose of sildenafil had a significant effect on increase in MWT but had no significant effects on PFWT and oxygenation parameters in patients with claudication. A double-blind, prospective, randomized, multicenter study (VIRTUOSE©) is ongoing to evaluate the chronic effect of six month-long sildenafil treatment on MWT in PAD patients with claudication.This clinical trial was registered at clinicaltrials.gov, registration. number: NCT02832570, (https://clinicaltrials.gov/ct2/show/NCT02832570).
- Published
- 2019
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