Chronic Clinical Effect of Acetazolamide (ChronicAZA)

Chronic Clinical Effect of Acetazolamide in Pulmonary Hypertension

The study seeks primarily to determine the chronic clinical effect of AZA on exercise capacity (6MWD) compared to placebo.

Study Overview

• Status: Completed
• Conditions: Hypertension, Pulmonary
• Intervention / Treatment: Drug: Placebo; Drug: Acetazolamide

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. We 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 chronic clinical effects of AZA in PH patients.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland, 8091
    • University Hospital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients undergoing right heart catheterisation (RHC) for a clinical indication and who are diagnosed with precapillary PH (mean pulmonary arterial pressure (mPAP) ≥25 mmHg, pulmonary wedge pressure (PAWP) ≤15mmHg)
• Patients have to be in a stable condition, on the same medication for >4 weeks

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acetazolamide; Twice a day 250 mg acetazolamide for 5 weeks	Drug: Acetazolamide
Placebo Comparator: Placebo; Placebo capsule 250 mg (Mannitol) twice a day 5 weeks	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in 6 min walk distance	At the end of both periods (AZA and Placebo)	5 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference of Quality of Life (QoL) assessed by the physical subscale of the living with pulmonary hypertension questionnaire (MLHF)	At the end of both periods (AZA and Placebo)	5 weeks
Progressive maximal ramp cardiopulmonary exercise testing	At the end of both periods (AZA and Placebo)	5 weeks
cerebral and muscle tissue oxygenation	At the end of both periods (AZA and Placebo) at rest and exercise	5 weeks
daily activity	actigraphy	5 weeks
morphological and functional parameters of the heart	measured by echocardiography	5 weeks
New York Heart Association functional class	At the end of both periods (AZA and Placebo)	5 weeks
Short-form medical outcome questionnaire (SF-36)	At the end of both periods (AZA and Placebo)	5 weeks
Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR)	At the end of both periods (AZA and Placebo)	5 weeks
N-terminal pro-brain natriuretic Peptide (NT-proBNP)	At the end of both periods (AZA and Placebo)	5 weeks
mean nocturnal oxygen Saturation during ambulatory sleep studies	At the end of both periods (AZA and Placebo)	5 weeks
apnea/hypopnea index during ambulatory sleep studies	At the end of both periods (AZA and Placebo)	5 weeks
Stroop test of cognitive performance	At the end of both periods (AZA and Placebo)	5 weeks
Trail making test (test of cognitive Performance)	At the end of both periods (AZA and Placebo)	5 weeks
5 point test (test of cognitive Performance)	At the end of both periods (AZA and Placebo)	5 weeks

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Principal Investigator: Silvia Ulrich, MD, UniversityHospital Zurich

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Actual): November 1, 2020
• Study Completion (Actual): November 1, 2020

Study Registration Dates

• First Submitted: March 24, 2016
• First Submitted That Met QC Criteria: April 25, 2016
• First Posted (Estimate): April 28, 2016

Study Record Updates

• Last Update Posted (Actual): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 17, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Acetazolamide; Treatment Outcome
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Natriuretic Agents; Diuretics; Anticonvulsants; Acetazolamide
• Other Study ID Numbers: KEK-ZH-2016-00089-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided