title: Study protocol: a phase III randomised, double-blind, parallel arm, stratified, block randomised, placebo-controlled trial investigating the clinical effect and cost-effectiveness of sertraline for the palliative relief of breathlessness in people with chronic breathlessness.
abstract: Breathlessness remains a highly prevalent and distressing symptom for many patients with progressive life-limiting illnesses. Evidence-based interventions for chronic breathlessness are limited, and there is an ongoing need for high-quality research into developing management strategies for optimal palliation of this complex symptom. Previous studies have suggested that selective serotonin reuptake inhibitors such as sertraline may have a role in reducing breathlessness. This paper presents the protocol for a large, adequately powered randomised study evaluating the use of sertraline for chronic breathlessness in people with progressive life-limiting illnesses.
  
  
  
  A total of 240 participants with modified Medical Research Council Dyspnoea Scale breathlessness of level 2 or higher will be randomised to receive either sertraline or placebo for 28 days in this multisite, double-blind study. The dose will be titrated up every 3 days to a maximum of 100 mg daily. The primary outcome will be to compare the efficacy of sertraline with placebo in relieving the intensity of worst breathlessness as assessed by a 0-100 mm Visual Analogue Scale. A number of other outcome measures and descriptors of breathlessness as well as caregiver assessments will also be recorded to ensure adequate analysis of participant breathlessness and to allow an economic analysis to be performed. Participants will also be given the option of continuing blinded treatment until either study data collection is complete or net benefit ceases. Appropriate statistical analysis of primary and secondary outcomes will be used to describe the wealth of data obtained.
  
  
  
  Ethics approval was obtained at all participating sites. Results of the study will be submitted for publication in peer-reviewed journals and the key findings presented at national and international conferences.
  
  
  
  ACTRN12610000464066.
authors.affiliation: Department of Palliative Care, Calvary Mater Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Gareth J
authors.identifier: 0000-0002-4317-7258
authors.initials: GJ
authors.lastname: Watts
authors.affiliation: Department of Palliative Care, Calvary Mater Newcastle, Newcastle, New South Wales, Australia.|School of Medicine and Public Health, The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Katherine
authors.initials: K
authors.lastname: Clark
authors.affiliation: Faculty of Health and Graduate School of Health, University of Technology Sydney, Sydney, New South Wales, Australia.|Clinical Trials, Ingham Institute of Applied Medical Research, Sydney, New South Wales, Australia.|Department of Palliative and Supportive Services, Flinders University, Adelaide, South Australia, Australia.|South West Sydney Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Meera
authors.initials: M
authors.lastname: Agar
authors.affiliation: Faculty of Health and Graduate School of Health, University of Technology Sydney, Sydney, New South Wales, Australia.|School of Nursing, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Davidson
authors.affiliation: Austin Health, Respiratory and Sleep Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
authors.forename: Christine
authors.initials: C
authors.lastname: McDonald
authors.affiliation: Faculty of Health and Graduate School of Health, University of Technology Sydney, Sydney, New South Wales, Australia.
authors.forename: Lawrence T
authors.identifier: 0000-0001-6183-6854
authors.initials: LT
authors.lastname: Lam
authors.affiliation: Australian Respiratory and Sleep Medicine Institute, Flinders Medical Centre, Adelaide, South Australia, Australia.
authors.forename: Dimitar
authors.identifier: 0000-0001-8864-254X
authors.initials: D
authors.lastname: Sajkov
authors.affiliation: Department of Palliative and Supportive Services, Flinders University, Adelaide, South Australia, Australia.
authors.forename: Nicola
authors.identifier: 0000-0003-3684-3723
authors.initials: N
authors.lastname: McCaffrey
authors.affiliation: Department of Clinical Pharmacology, University of Otago, Christchurch, New Zealand.
authors.forename: Matthew
authors.initials: M
authors.lastname: Doogue
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Amy P
authors.identifier: 0000-0001-6930-8722
authors.initials: AP
authors.lastname: Abernethy
authors.affiliation: Department of Palliative and Supportive Services, Flinders University, Adelaide, South Australia, Australia.
authors.forename: David C
authors.initials: DC
authors.lastname: Currow
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D003362:Cost-Benefit Analysis; D004311:Double-Blind Method; D004417:Dyspnea / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010166:Palliative Care / Q000379:methods*; D012044:Regression Analysis; D012107:Research Design; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D020280:Sertraline / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D064232:Visual Analog Scale; D055815:Young Adult
chemical_list: D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline
keywords: PALLIATIVE CARE; breathlessness; protocol; randomised control trial; sertraline