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Magnesium Oral Supplementation to Reduce Pain Inpatients With Severe Peripheral Arterial Occlusive Disease

Not Applicable
Conditions
Peripheral Arterial Disease
Interventions
Dietary Supplement: Fructose
Dietary Supplement: Magnesium oxide
Registration Number
NCT02455726
Lead Sponsor
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Brief Summary

Magnesium exerts analgesic effects in several animal pain models and in patients affected by acute postoperative pain and chronic pain of neuropathic origin. There is no evidence that magnesium can modulate pain in patients with peripheral arterial occlusive disease (PAOD).

We describe the protocol of a single-center randomized double-blind clinical trial aimed at assessing the efficacy of oral magnesium supplementation in controlling severe pain in patients with advanced PAOD.

Detailed Description

* Adult patients admitted to our Acute Pain Service for intractable pain will be eligible if they are affected by PAOD at stages III and IV of Lèriche-Fontaine classification, and are opioid-naïve.

* Patients enrolled will be randomized to the control group, treated with standard therapy, consisting of an oral administration of oxycodone 5 mg and pregabalin 25 mg per day plus placebo (fructose 10 g) twice a day for two weeks, or to the experimental group, treated with magnesium oxide 300 mg twice a day.

* Randomization will be computer-generated, with allocation concealment obtained using opaque, sequentially numbered and sealed envelopes. Trials participants, care providers, data collectors, outcome assessors and data analysts will be blinded to treatment allocation.

* Patients will be evaluated on the day of hospital admission (day 0) and on days 2, 4, 6, 8, 12, and 14 with the following information being collected: daily oxycodone dose received; patient's perceived average and maximum pain using the Numerical Rating Scale (NRS: 0=no pain to 10=worst possible pain); pain relief using Pain Relief Scale (PRS: 0% no pain relief to 100% complete pain relief); characteristics of the pain, using the Neuropathic Pain Scale (NPS: 10 items); impact of pain on the patient's daily activities, using the Brief Pain Inventory (BPI; 9 items).

* A sample size calculation performed for the primary outcome showed that 150 patients (75 per group) are needed to achieve 90% power to detect a minimum reduction of 30% in oxycodone dosage in the experimental group, after allowing for a drop-out rate of around 20%.

* Ethical approval of the study protocol has been obtained from Comitato Etico Provinciale di Brescia, Brescia, Italy.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
150
Inclusion Criteria
  • adult patients (18 years or above)
  • PAOD at stages III and IV according to the Lèriche-Fontaine classification
  • no treatment with opioids at the time of recruitment
Exclusion Criteria
  • renal failure (serum creatinine ≥ 2.0 mg/dl);
  • congestive heart failure (New York Heart Association, NYHA > 3);
  • treatment with digoxin and/or calcium channel blockers;
  • pre-existing neuromuscular diseases;
  • chronic diarrhea;
  • acute limb ischemia successfully treated with interventional angiography, Fogarty embolectomy and/or surgical revascularization.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
C-groupFructoseStandard therapy plus fructose. * Standard therapy: oxycodone 5 mg and pregabalin 25 mg per day for two weeks. Starting by day 2, the opioid dose will be titrated every 48 hours in order to reach the maximum therapeutic goal and to minimize side effects. * A rescue dose: paracetamol 1g (maximum dose 3 g per day).
Mg-groupMagnesium oxideStandard therapy plus magnesium oxide. * Standard therapy: oxycodone 5 mg and pregabalin 25 mg per day for two weeks. Starting by day 2, the opioid dose will be titrated every 48 hours in order to reach the maximum therapeutic goal and to minimize side effects. * A rescue dose: paracetamol 1g (maximum dose 3 g per day).
Mg-groupPregabalinStandard therapy plus magnesium oxide. * Standard therapy: oxycodone 5 mg and pregabalin 25 mg per day for two weeks. Starting by day 2, the opioid dose will be titrated every 48 hours in order to reach the maximum therapeutic goal and to minimize side effects. * A rescue dose: paracetamol 1g (maximum dose 3 g per day).
Mg-groupOxycodoneStandard therapy plus magnesium oxide. * Standard therapy: oxycodone 5 mg and pregabalin 25 mg per day for two weeks. Starting by day 2, the opioid dose will be titrated every 48 hours in order to reach the maximum therapeutic goal and to minimize side effects. * A rescue dose: paracetamol 1g (maximum dose 3 g per day).
C-groupOxycodoneStandard therapy plus fructose. * Standard therapy: oxycodone 5 mg and pregabalin 25 mg per day for two weeks. Starting by day 2, the opioid dose will be titrated every 48 hours in order to reach the maximum therapeutic goal and to minimize side effects. * A rescue dose: paracetamol 1g (maximum dose 3 g per day).
C-groupPregabalinStandard therapy plus fructose. * Standard therapy: oxycodone 5 mg and pregabalin 25 mg per day for two weeks. Starting by day 2, the opioid dose will be titrated every 48 hours in order to reach the maximum therapeutic goal and to minimize side effects. * A rescue dose: paracetamol 1g (maximum dose 3 g per day).
Primary Outcome Measures
NameTimeMethod
The oxycodone dosage needed to achieve satisfactory analgesia14 days

Patient's satisfactory analgesia is defined as NRS ≤4

Secondary Outcome Measures
NameTimeMethod
Time to 50% reduction of painfrom 2 to 14 days

The time needed to achieve a reduction of pain of 50% using Pain Relief Scale(PRS = 50%)

Level of pain relief2 days

The level of pain relief is measured using Pain Relief Scale

Time to satisfactory analgesiafrom 2 to 14 days

The time needed to achieve satisfactory analgesia (NRS≤4)

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