title: MAGnesium-oral supplementation to reduce PAin in patients with severe PERipheral arterial occlusive disease: the MAG-PAPER randomised clinical trial protocol.
abstract: BACKGROUND
  Magnesium exerts analgaesic effects in several animal pain models, as well as in patients affected by acute postoperative pain and neuropathic chronic pain. There is no evidence that magnesium can modulate pain in patients with peripheral arterial occlusive disease (PAOD). We describe the protocol of a single-centre randomised double-blind clinical trial aimed at assessing the efficacy of oral magnesium supplementation in controlling severe pain in patients with advanced PAOD.
  
  
  METHODS
  Adult patients affected by PAOD at stages III and IV of Lèriche-Fontaine classification, who are opioid-naïve, and who have been admitted to our Acute Pain Service for intractable pain, will be eligible. Patients will be randomised to the control group, treated with standard therapy (oxycodone and pregabalin) plus placebo for 2 weeks, or to the experimental group (standard therapy plus magnesium oxide). Patients will be evaluated on days 0, 2, 4, 6, 8, 12 and 14; the following information will being collected: daily oxycodone dose; average and maximum pain (Numerical Rating Scale); pain relief (Pain Relief Scale); characteristics of the pain (Neuropathic Pain Scale); impact of pain on the patient's daily activities (Brief Pain Inventory). The primary outcome will be oxycodone dosage needed to achieve satisfactory analgaesia on day 14. Secondary outcomes will be pain relief on day 2, time needed to achieve satisfactory analgaesia and time needed to achieve a pain reduction of 50%. A sample size calculation was performed for the primary outcome, which estimated a required sample size of 150 patients (75 per group).
  
  
  BACKGROUND
  Ethical approval of the study protocol has been obtained from Comitato Etico Provinciale di Brescia, Brescia, Italy. Trial results will be disseminated through scientific journal manuscripts and scientific conference presentations.
  
  
  BACKGROUND
  NCT02455726.
authors.affiliation: Department of Anesthesia, Critical Care Medicine and Emergency, University of Brescia at Spedali Civili, Brescia, Italy.
authors.forename: Monica Aida
authors.initials: MA
authors.lastname: Venturini
authors.affiliation: Department of Anesthesia, Critical Care Medicine and Emergency, University of Brescia at Spedali Civili, Brescia, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Zappa
authors.affiliation: National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Cosetta
authors.initials: C
authors.lastname: Minelli
authors.affiliation: Department of Surgery, University of Brescia at Spedali Civili, Brescia, Italy Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonardelli
authors.affiliation: Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Lamberti
authors.affiliation: Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Bisighini
authors.affiliation: Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Zangrandi
authors.affiliation: Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Turin
authors.affiliation: Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Rizzo
authors.affiliation: Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rizzolo
authors.affiliation: Department of Anesthesia, Critical Care Medicine and Emergency, University of Brescia at Spedali Civili, Brescia, Italy Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Latronico
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D001157:Arterial Occlusive Diseases / Q000150:complications*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007558:Italy; D016014:Linear Models; D008274:Magnesium / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010098:Oxycodone / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D000069583:Pregabalin / Q000627:therapeutic use*; D012107:Research Design; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D000069583:Pregabalin; D010098:Oxycodone; D008274:Magnesium
keywords: VASCULAR MEDICINE; VASCULAR SURGERY