Acute Hemodynamic Effect of Acetazolamide in Pulmonary Hypertension

Phase 2

Completed

• Conditions: Hypertension, Pulmonary
• Interventions: Drug: Placebo; Drug: Acetazolamide

• Registration Number: NCT02755259
• Lead Sponsor: University of Zurich

Brief Summary

To study the acute effect of acetazolamide (AZA) on pulmonary hemodynamics in patients with pulmonary hypertension (PH) undergoing clinically indicated right heart catheterisation (RHC).

Detailed Description

Pulmonary hypertension (PH) of various etiologies causes dyspnea, impairs exercise performance and is associated with reduced quality of life (QoL) and survival. Treatment options include therapy for any underlying causes, pulmonary vasodilator drugs, oxygen and, in selected cases, pulmonary endarterectomy or lung transplantation. Unfortunately, PH specific drugs are expensive, associated with side effects and even combined pharmacological treatment is often not sufficient to achieve clinical benefits. Therefore, novel therapeutic drugs are needed. The investigators have recently demonstrated that sleep related breathing disorders, which are common in PH patients, can be improved by both nocturnal oxygen therapy and acetazolamide (AZA). AZA is a carbonic anhydrase (CA) inhibitor that acts as a respiratory stimulant thereby improving oxygenation and possibly PH. There are even data suggesting that CA-inhibitors have a direct pulmonary vasodilator effect. However, the potential role of AZA in the treatment of PH has not been conclusively studied. Therefore, the purpose of the current project is to investigate, the acute hemodynamic clinical effects of AZA in PH patients.

Study Timeline

• Study First Submitted: 2016-03-24
• Study First Submitted QC: 2016-04-25
• Study First Posted: 2016-04-28
• Study Start: 2017-01-01
• Primary Completion: 2019-04-05
• Study Completion: 2019-04-05
• Status Verified: 2019-08
• Last Update Submitted: 2019-08-12
• Last Update Posted: 2019-08-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 33

Inclusion Criteria

• All patients undergoing RHC for a clinical indication and who are diagnosed with precapillary PH (mPAP ≥25 mmHg, pulmonary wedge pressure (PAWP) ≤15mmHg)

Exclusion Criteria

• Patients in whom a RHC is clinically not indicated
• pregnant women
• PH in left heart disease or with more than mild chronic obstructive pulmonary disease or restrictive lung disease.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo Saline injection (1x)
Acetazolamide	Acetazolamide	Diamox 500mg i.v. (1x)

Primary Outcome Measures

Name	Time	Method
Pulmonary vascular resistance (PVR) AZA vs. Placebo (rest)	60 minutes	At the end of phase at rest
PVR AZA vs. Placebo (exercise)	60 minutes	At the end of phase at exercise
PVR AZA vs. Placebo (hypoxia)	60 minutes	At the end of phase under hypoxia

Secondary Outcome Measures

Name	Time	Method
cardiac output	60 minutes	At the end of each phase (rest, exercise and hypoxia)
cardiac index	60 minutes	At the end of each phase (rest, exercise and hypoxia)
pulmonary wedge pressure	60 minutes	At the end of each phase (rest, exercise and hypoxia)
Borg scale dyspnea and leg effort	15 minutes
partial pressure of the oxygen	60 minutes	At the end of each phase (rest, exercise and hypoxia)
Oxygen uptake	15 minutes
minute ventilation	15 minutes
arterial oxygenation	60 minutes	At the end of each phase (rest, exercise and hypoxia)
tissue oxygenation	60 minutes	At the end of each phase (rest, exercise and hypoxia)
mean pulmonary arterial pressure	60 minutes	At the end of each phase (rest, exercise and hypoxia)

Trial Locations

Locations (1)

University Hospital Zurich; 🇨🇭 Zurich, Switzerland