None listed
Conditions
Brief summary
Dyspnoea, defined as an uncomfortable sensation of breathing (which is often reported by patients as breathlessness), is a common symptom affecting up to 80% of cancer patients and 95% of patients with chronic obstructive pulmonary disease (COPD). Nearly half of all patients requiring palliative care report breathlessness as a problem during the last year of life. Moreover, dyspnoea is consistently high-lighted as a poor prognostic factor and harbinger of impending death. Ventilatory drive is the net result of complex automatic and subconscious, peripheral and central, neural and chemical mechanisms. Dyspnoea is the conscious perception which has taken account of the net result of those mechanisms and integrated it with other cognitive and emotive factors that are also affecting the individual. Dyspnoea is thus a subjective symptom that is debilitating to patients, impacting greatly on quality of life of both patient and carer. It is a challenging symptom to manage and is often impossible to reverse despite maximal treatment of the underlying cause. Anxiety is often reported by patients as a major component of breathlessness with breathlessness leading to anxiety and anxiety exacerbating breathlessness leading to a progressive spiral of cause and effect. Hypothesis : Intranasal midazolam is superior to placebo for the palliation of dyspnoea in patients with optimally treated life limiting disease
Interventions
Intra-nasal midazolam. Each participant will receive six identical spray bottles, three will contain midazolam, and three citric acid in Normal saline. The six nasal spray bottles will be numbered 1-6 and will contain either midazolam or placebo (Citric acid in Normal saline) in a random sequence. Participants will be instructed to use a total of 3 inhalations (total dose of 1.5mg active drug) no more frequently than every 4 hours. This dose is administered as 1 spray in alternating nostrils for
Intra-nasal midazolam. Each participant will receive six identical spray bottles, three will contain midazolam, and three citric acid in Normal saline. The six nasal spray bottles will be numbered 1-6 and will contain either midazolam or placebo (Citric acid in Normal saline) in a random sequence. Participants will be instructed to use a total of 3 inhalations (total dose of 1.5mg active drug) no more frequently than every 4 hours. This dose is administered as 1 spray in alternating nostrils for 3 administrations. Participants will be asked to use a study nasal spray(SNS) as their first rescue dose for dyspnoea on any day that they require a rescue dose (starting no earlier than 0600hrs), taking number 1 SNS on the first day, number 2 on the second day, number 3 on the third etc, provided no SNS has been used for 4 hours prior, or breakthrough pain medication within 6 hours. If patients do not experience dyspnoea, they are not required to use a SNS that day. Only the first dose each day will be formally assessed, but participants can continue to use the SNS throughout the day (no more frequently than every 4 hours) if they find it useful. All SNS must be used within 14 days. Washout is at least 6 hours.
Sponsors
Arohanui Hospice Service Trust, Clare Randall as representative
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants must: be at least 18 years of age have dyspnoea related to life-limiting disease or its treatment have a dyspnoea score >3/10 on at least 3 occasions during the previous week be English speaking or have an interpreter available have an adequate performance status Australian Karnofsky Performance Scale (AKPS >30) be able to operate a nasal spray device be able to understand all trial requirements and complete a dyspnoea diary have had no changes in any medication likely to affect dyspnoea (eg steroids, opioids) within 48 hours of starting the study
Exclusion criteria
Patients will be excluded in the case of: an acute respiratory event likely to resolve eg. chest infection, acute exacerbation of asthma concurrent treatment with an unstable dose of benzodiazepines (excluding nocturnal sedation) concurrent treatment with an unstable dose of opioids (change in baseline dose within 48 hours of study entry or during the duration of the study) regular use (greater than 3 times/day) of breakthrough opioids for pain or dyspnoea that would interfere with assessment of benefit of the midazolam spray a previous adverse reaction to benzodiazepines concurrent treatment with itraconazole or ketoconazole respiratory depression (resting respiratory rate (RR) <10 breaths/minute) co-morbid myasthenia gravis, or acute narrow angle glaucoma an alcohol and/or drug dependency problem any intervention or change in therapy likely to effect dyspnoea during the study period or in the 2 weeks prior (this includes radiotherapy to the lung and/or chemotherapy or blood transfusion 72 hours prior with the potential to effect dyspnoea ) any change in oxygen prescription during the study period
Outcome results
None listed