Clinical trial NCT02790450: Acute Effects of Benzbromaron on the Pulmonary Circulation
Official title: Acute Effects of Benzbromaron on the Pulmonary Circulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Idiopathic Pulmonary Arterial Hypertension
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
Collaborators: name: Ludwig Boltzmann Institute for Lung Vascular Research
First posted: 2016-06-03
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Actual studies suggest that a calcium activated chlorid channel (TMEM16A) may play a relevant role in the pathogenesis of pulmonary arterial hypertension (PAH). The inhibition of this channel led to pulmonary vasorelaxation in preclinical studies. Benzbromarone is a well known inhibitor of the TMEM16A channel and is used in patients with gout.

In this pilot study the investigators plan to investigate if Benzbromarone has an acute effect on the pulmonary arteries in humans. This will be investigated within the frame of a right heart catheterization performed in patients with known PAH due to clinical reasons. The investigators hypothesize that the application of Benzbromarone leads to pulmonary vasodilation, which can be recognized by the decrease in pulmonary vascular resistance. In addition, the change in pulmonary and systemic arterial pressure, pulmonary arterial wedge pressure, heart rate and arterial oxygen saturation will be assessed. Due to clinical reasons patients will receive NO (15 ppm) during right heart catheterization. Hemodynamic changes upon NO and Benzbromarone may be compared.


Eligibility criteria: Inclusion Criteria:

* written informed consent
* known pulmonary arterial hypertension
* right heart catheterization indicated due to clinical reasons

Exclusion Criteria:

* known allergy against Benzbromaron, Gelborange S or other ingredient of the used drug (Benzbromarone AL) or a drug with similar chemical structure
* severe renal insufficiency (GFR\<30ml/min/kg)
* renal diathesis
* severe hepatic disease (Bilirubin \>1.6 mg% or AST or ALT \> 3x Norm)
* known pregnancy
* uncontrolled systemic arterial hypertension (\>150 mmHg systolic or 95 mmHg diastolic)
* uncontrolled ventricular arrythmia
* uncontrolled bradycardic or tachycardic supraventricular arrythmia
* myocardiac infarction within the last 12 months
* pulmonary embolism within the last 6 months
* ongoing iv. or sc. Prostanoid therapy for PAH
* Pulmonary hypertension other than PAH

Primary outcomes:
measure: Pulmonary vascular resistance (Wood units) assessed by right heart catheterization
timeFrame: 2 hours
Secondary outcomes:
measure: Mean pulmonary arterial pressure (mmHg) assessed by right heart catheterization
timeFrame: 2 hours
measure: Mean systemic arterial pressure (mmHg) assessed by sphygmomanometer
timeFrame: 2 hours
measure: arterial oxygen saturation 8%) assessed by arterial blood gas analysis
timeFrame: 2 hours
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University of Graz
Study officials:
affiliation: Medical University of Graz
name: Horst Olschewski, MD
role: PRINCIPAL_INVESTIGATOR
References: