Midazolam Nasal Spray for the treatment of breathlessness in patients with life-limiting disease

Phase 3

• Conditions: Other - Conditions of unknown or disputed aetiology (such as chronic fatigue syndrome/myalgic encephalomyelitis); Dyspnoea (Breathlessness)

• Registration Number: ACTRN12609000506291
• Lead Sponsor: Arohanui Hospice Service Trust, Clare Randall as representative

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2009-06-25
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Stopped early
• Sex: All
• Target Recruitment: 200

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary outcome is dyspnoea intensity difference (DID) between active drug and placebo, measured by recording dyspnoea score on an 11-point Numerical Rating Scale (NRS) anchored at 0 = no breathlessness to 10 = worst possible breathlessness.[The primary end point will be the mean of the dyspnoea intensity difference (DID) at 15 minutes after each dose, compared to baseline (DID15-DID0)]

Secondary Outcome Measures

Name	Time	Method
DID at 5, 30 and 60 mins, measured by recording dyspnoea score on an 11-point Numerical Rating Scale (NRS) anchored at 0 = no breathlessness to 10 = worst possible breathlessness.[DID at 5, 30 and 60 mins following the first dose of SNS each day];sedation (using difference in mean NRS score of placebo compared to midazolam)on 11-point NRS anchored at 0= not at all drowsy to 10= extremely drowsy[0, 5, 15, 30 and 60 mins following the first dose of SNS each day];anxiety scored on an 11-point NRS anchored at 0= not at all anxious to 10= extremely anxious[0, 5, 15, 30 and 60 mins following the first dose of SNS each day];General impression of benefit - scored in patient diary on 5-point scale where 0=no benefit to 4=excellent benefit[Daily when study spray used];Pain scored on an 11-point NRS where Pain right now is scored using a NRS anchored at 0= no pain to 10= worst possible pain[0, 5, 15, 30 and 60 mins following the first dose of SNS each day]