None listed
Conditions
Brief summary
Pulmonary hypertension (PH) is a disease in which blood pressure in lung circulation is abnormally high. PH remains highly-debilitating and deadly – half of patients may die within 5-years of diagnosis. Therefore, new PH treatments are urgently needed. This project builds on discovery by our group that medications working through "beta3 adrenergic receptors" reduce blood pressure in lung circulation of laboratory animals. This study aims to assess the safety and effect of mirabegron - a medication from this family that is used for overactive bladder in Australia – in adult patients with PH. We will administer mirabegron at the hospital and closely monitor the patients. We will measure the blood pressure in the lung circulation using special catheters that are routinely used for this purpose. If mirabegron is safe and effective, we will prescribe it for 8 days and assess the effects by ultrasound of heart in follow-up.
Interventions
Participants in Part A of the study will receive 25 mg Mirabegron as a single oral dose at the hospital.
In Part B, 50 mg Mirabegron will be given orally as a single dose at the hospital. Mirabegron will then be continued as a daily dose for 8 days as an outpatient. The adherence in the outpatient setting in Part B will be monitored by drug tablet return.
Part B of the study will commence after completion of Part A, if Mirabegron is proven to be safely tolerated by patients in Part A.
Inclu
Participants in Part A of the study will receive 25 mg Mirabegron as a single oral dose at the hospital. In Part B, 50 mg Mirabegron will be given orally as a single dose at the hospital. Mirabegron will then be continued as a daily dose for 8 days as an outpatient. The adherence in the outpatient setting in Part B will be monitored by drug tablet return. Part B of the study will commence after completion of Part A, if Mirabegron is proven to be safely tolerated by patients in Part A. Inclusion and exclusion criteria are the same for Part A and B of the study.
Sponsors
Royal Prince Alfred Hospital
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
19 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
We will enrol patients with a diagnosis of PH that fulfil all of the following criteria: A- PH due to following aetiologies/diagnostic classifications: - Group 1 pulmonary hypertension - Chronic pulmonary hypertension due to inoperable small distal pulmonary emboli (also known as CTEPH AND B-The patient is: -PH treatment naïve or, -on an endothelin receptor antagonist (ERA) (Bosentan, Macitentan or Ambrisentan) as monotherapy, or, - on combination therapy with an ERA (Bosentan, Macitentan or Ambrisentan) plus an agent in the NO pathway (Sildenafil, Tadalafil or Riociguat) when the NO-related therapy can be safely withheld in short-term AND C-The right heart catheterisation is clinically indicated. AND D- The participant does not meet any of the exclusion criteria
Exclusion criteria
• Significant hepatic (transaminases or bilirubin x 3 above upper reference level) or renal impairment (GFR< 30 ml/min/1,73 m2). • Significant hypotension (defined as symptomatic systolic blood pressure < 80 mmHg) or hypertension (defined as systolic >180 mmHg and/or diastolic blood pressure >110 mmHg). • Right heart failure defined with PH associated with systemic venous congestion and fluid retention (e.g. peripheral oedema, ascites) • Left heart failure (LVEF <50% and clinical signs of left heart failure). • Severe interstitial lung disease with forced vital capacity (FVC) < 70% • Congenital or drug-induced QT prolongation. • Patients with known bladder outlet obstruction and patients taking antimuscarinic medications for overactive bladder syndrome. • Anaemic patients with Hb <100 mg/dL and iron deficiency or gastrointestinal bleed within 6 months. • Treatment with a tricyclic antidepressant or CYP2D6 substrates other than beta-blockers or treatment with digoxin. • Pregnancy in female participants : female subjects of childbearing potential must have a pregnancy test performed with negative results known within 7 days prior to the index procedure. • Breast feeding in female participants: female subject is not breastfeeding at the time of the screening visit and will not be breast-feeding at the time of the study. • Subject has participated in another study during the 30 days preceding the current study. • Hypersensitivity(allergic reaction) to inhaled nitric oxide • Subject is part of a vulnerable population who, in the judgment of the investigator, is unable to give Informed Consent for reasons of incapacity, immaturity, adverse personal circumstances or lack of autonomy.This may include: Individuals with mental disability, persons in nursing homes, children, impoverished persons, persons in emergency situations, homeless persons, nomads, refugees, and those incapable of giving informed consent. Vulnerable populations also may include members of a group with a hierarchical structure such as university students, subordinate hospital and laboratory personnel, members of the armed forces, and persons kept in detention.
Outcome results
None listed