Acute Effects of Benzbromaron on the Pulmonary Circulation

NCT02790450 | Completed Phase 2 DMC

• 1 other identifier: 27-253 ex 14/15
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Idiopathic Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (1)

• Pulmonary vascular resistance (Wood units) assessed by right heart catheterization

  2 hours

Secondary Outcomes (3)

• Mean pulmonary arterial pressure (mmHg) assessed by right heart catheterization

  2 hours

• Mean systemic arterial pressure (mmHg) assessed by sphygmomanometer

  2 hours

• arterial oxygen saturation 8%) assessed by arterial blood gas analysis

  2 hours

Study Arms (1)

Benzbromarone

EXPERIMENTAL

1x200mg Benzbromarone

Drug: Benzbromarone

Interventions

Benzbromarone DRUG

1x200mg Benzbromarone will be applied after baseline measurements during right heart catheterization. The effects of the drug on the pulmonary hemodynamics will be assessed after 2 hours.

Benzbromarone

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Graz: lead
• Ludwig Boltzmann Institute for Lung Vascular Research: collaborator

Study Sites (1)

Medical University of Graz

Graz, 8036, Austria

Location

MeSH Terms

Conditions

Familial Primary Pulmonary Hypertension

Interventions

Benzbromarone

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Horst Olschewski, MD

  Medical University of Graz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2016
• First Posted: June 3, 2016
• Study Start: October 1, 2015
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: December 23, 2016

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)