title: Short-term opioids for breathlessness in stable chronic heart failure: a randomized controlled trial.
abstract: OBJECTIVE
  To assess the effect of oral opioids vs. placebo on breathlessness in patients with chronic heart failure (CHF).
  
  
  RESULTS
  Oral morphine (Oramorph), oral oxycodone (Oxynorm), and placebo were studied in an outpatient setting. Once randomized, participants received all three interventions in a controlled double-blind crossover trial for 4 days each, with a 3-day washout between interventions. Patients known to the Hull and East Yorkshire Academic Cardiology department with CHF (New York Heart Association Grade III-IV) were invited to participate. Participants were eligible if they were on standard medical therapy with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and diuretics. Participant-rated change in 11-point numerical rating scale (NRS) (average over previous 24 h) breathlessness severity score from baseline (Day 1) to Day 4 of treatment was the primary outcome measure. The study was powered to detect a one-point change in severity.Thirty-nine patients were randomized and 35 completed all three study arms. Breathlessness severity was reduced from baseline with all three interventions. There was no statistically significant difference between active intervention and placebo or between the two types of opioid for the primary endpoint [-1.37 in NRS score for placebo group vs. -0.41 in morphine group (P = 0.13) and -1.29 for oxycodone group (P = 0.90)]. The response to treatment was not affected by aetiology, severity of CHF, or concurrent drug therapy. Opioid administration did not cause detrimental changes in clinical observations and was well tolerated.
  
  
  CONCLUSIONS
  We demonstrated no benefit over placebo for the relief of breathlessness with short-term low-dose oral opioids for CHF patients. Trial registered prior to the recruitment of the first participant with Current Controlled Trials (www.controlled-trials.com; Trial number ISRCTN 85268059).
authors.affiliation: Department of Health Sciences, Hull York Medical School, York University, Heslington, York YO10 5DD, UK. Stephen.Oxberry@hyms.ac.uk
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Oxberry
authors.forename: David J
authors.initials: DJ
authors.lastname: Torgerson
authors.forename: J Martin
authors.initials: JM
authors.lastname: Bland
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Clark
authors.forename: John G F
authors.initials: JG
authors.lastname: Cleland
authors.forename: Miriam J
authors.initials: MJ
authors.lastname: Johnson
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004417:Dyspnea / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use; D010098:Oxycodone / Q000008:administration & dosage / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D009020:Morphine; D010098:Oxycodone