A Pilot Phase II Randomized, Cross-Over, Double-Blinded, Controlled Efficacy Study of Octreotide versus Hyoscine Hydrobromide for Control of Noisy Breathing at the End-of-Life

Abstract

Noisy breathing at the end of life (noisy breathing (“NB”) occurs in up to 90% of people. Interventions have not been systematically evaluated. There has been clinical observation coupled with a proposed mechanism of effect that supports a role for octreotide in management of NB. The aim of this phase II study was to assess ten completed participants for the feasibility of an adequately powered phase III study. This randomized, double-blind, crossover pilot trial recruited participants from an inpatient palliative unit. Participants while well and their proxies simultaneously provided written informed consent. If NB were encountered, people were randomized to 200 mcg octreotide or 400 mcg hyoscine hydrobromide subcutaneously. If subsequent treatment was needed, the other medication was administered. A five point categorical scale documented the nurses' assessment of secretions over six hours. Eighty participants were consented of whom 10 (3 females, 7 males; median age 79, all with advanced cancer) received medication, five in each arm. There was no difference in the median time to administration of the second medication (3 hours). Two participants in each arm had a 2 category reduction of intensity after the second medication. Although feasible to consent and study this population in a way that respects autonomy and dignity even in the terminal hours of life, this pilot study suggests reconsideration of the pharmacological interventions (choice of agents, dosing, timing of dosing and pharmacokinetic profiles), standardizing of non-pharmacological care; and ways to measure directly family distress before further randomized studies for this symptom.