RecruitingPhase 3ACTRN12609000209291

Opioids for breathlessness in people with primary hypertension.

Randomised, placebo-controlled, double-blind, cross-over study of the efficacy of sustained-release low dose morphine in the subjective sensation of dyspnoea due to maximally treated primary pulmonary hypertension in opioid naive participants.


Sponsor

Flinders University - Department of Palliative and Support Services

Enrollment

40 participants

Start Date

Apr 21, 2009

Study Type

Interventional

Conditions

Summary

Dyspnoea is a source of physical and psychological distress, and is one of the most commonly feared aspects of the dying process. By definition, people with severe primary pulmonary hypertension have breathlessness, despite maximal therapy and recent advances in therapies for primary pulmonary hypertension. In parallel with attempting to treat the underlying pathology causing breathlessness, the sensation of breathlessness itself must be ameliorated. For many participants there comes a point when there are no further identifiable reversible components of the disease and the full focus of care moves to reducing the subjective sensation of breathlessness. Opioids have been studied for the relief of breathlessness predominantly in people with chronic obstructive pulmonary disease although people with cancer and heart failure have been included. [Abernethy, Miriam Johnson] A meta-analysis verified that overall there is benefit from the use of morphine in people with refractory breathlessness. [Jennings] This prospective, randomised, placebo-controlled, double-blind, cross-over study is modelled on a study successfully undertaken by some members of this research team. The study proposes to specifically study people with primary pulmonary hypertension for whom breathlessness is a significant symptomatic problem to establish whether there is benefit from sustained release morphine, and if so, what magnitude of benefit, and the clinical characteristics of those who are most likely to respond to this intervention. Any toxicity will also be carefully monitored.Study participants will receive either Kapanol 20mg and Coloxyl and Senna 1 to 2 tablets, or kapanol placebo and coloxyl and senna placebo for one week, will receive no intervention medication for the second week then will receive the alternative intervention combination for the third week.


Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria2

  • English speaking. Participants over the age of 18.Dyspnoea secondary to maximally medically treated primary pulmonary
  • hypertension as assessed by the person’s respiratory physician. New York Heart Association heart failure grade III or IV.Renal function - calculated creatinine clearance >10mmol/l. Haemoglobin > 10 g/dl, or treating clinician has reviewed the haemoglobin result and confirmed that patient is on maximal treatment. On stable oxygen - no changes to prescription in the last 7 days. On stable medications – no changes to prescription medications in the last 7 days. Able to complete participant diary.Willing and able to give informed consent.

Exclusion Criteria4

  • Taking regular opioid medications.True adverse reaction(s) to morphine previously. Known hypersensitivity to any of the morphine sulphate capsule components. History of central hypoventilation syndrome.
  • Use of monoamine oxidase inhibitor(s) (MAOIs) in the last 2 weeks or proposed use during the study.Australian Karnofsky Modified Performance Status (modified AKPS) < 50. Acutely confused (Nursing Delirium Assessment Scale score > 0 at baseline).Cognitive impairment (Mini-Mental State Examination < 24 at baseline). Uncontrolled nausea or vomiting.
  • Gastrointestinal obstruction.Pregnancy, risk of pregnancy or breast feeding mothers.
  • Past history of significant illicit opioid misuse.

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Interventions

One capsule of sustained- release Morphine 20mg taken orally, daily for 7 days, 1-2 tablets of Coloxyl and Senna taken orally, daily for 7 days, then a washout period of one week.

One capsule of sustained- release Morphine 20mg taken orally, daily for 7 days, 1-2 tablets of Coloxyl and Senna taken orally, daily for 7 days, then a washout period of one week.


Locations(1)

Austin Health - Austin Hospital - Heidelberg

Australia

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ACTRN12609000209291