Clinical trial NCT02755298: Chronic Clinical Effect of Acetazolamide
Official title: Chronic Clinical Effect of Acetazolamide in Pulmonary Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hypertension, Pulmonary
Keywords: Treatment Outcome
Acetazolamide
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2016-04-28
Enrollment: 24
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Difference in 6 min walk distance
timeFrame: 5 weeks
Secondary outcomes:
measure: Difference of Quality of Life (QoL) assessed by the physical subscale of the living with pulmonary hypertension questionnaire (MLHF)
timeFrame: 5 weeks
measure: Progressive maximal ramp cardiopulmonary exercise testing
timeFrame: 5 weeks
measure: cerebral and muscle tissue oxygenation
timeFrame: 5 weeks
measure: daily activity
timeFrame: 5 weeks
measure: morphological and functional parameters of the heart
timeFrame: 5 weeks
measure: New York Heart Association functional class
timeFrame: 5 weeks
measure: Short-form medical outcome questionnaire (SF-36)
timeFrame: 5 weeks
measure: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR)
timeFrame: 5 weeks
measure: N-terminal pro-brain natriuretic Peptide (NT-proBNP)
timeFrame: 5 weeks
measure: mean nocturnal oxygen Saturation during ambulatory sleep studies
timeFrame: 5 weeks
measure: apnea/hypopnea index during ambulatory sleep studies
timeFrame: 5 weeks
measure: Stroop test of cognitive performance
timeFrame: 5 weeks
measure: Trail making test (test of cognitive Performance)
timeFrame: 5 weeks
measure: 5 point test (test of cognitive Performance)
timeFrame: 5 weeks
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Zurich
Study officials:
affiliation: UniversityHospital Zurich
name: Silvia Ulrich, MD
role: PRINCIPAL_INVESTIGATOR
References: