Chronic Thromboembolic Pulmonary Hypertension, Pulmonary Arterial Hypertension
Conditions
Brief summary
The purpose of this study is to investigate the effects of dapagliflozin on exercise capacity and hemodynamics in patients with pulmonary arterial hypertension
Detailed description
The objective of this study is to evaluate the effects of oral dapagliflozin (Forxiga®) treatment versus placebo in clinically stable patients with pulmonary arterial hypertension or CTEPH on background vasodilator combination therapy on cardio-pulmonary exercise capacity, pulmonary vascular hemodynamics, RV function and metabolomic profile of the pulmonary vascular endothelium.
Interventions
Dapagliflozin 10 mg given once daily for three months
DRUGPlacebo
Matching placebo
Sponsors
Mads Ersbøll
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A diagnosis of PAH group 4 or group 1 in any of the following subtypes: * Idiopathic PAH (iPAH) * Heritable PAH (hPAH) * Connective tissue disease associated PAH (aPAH) * Associated with congenital heart disease (aPAH) * In case of PH in group 4, no further invasive treatment including pulmonary endarterectomy or pulmonary balloon angioplasty must be planned at time of inclusion. * Symptomatic PAH in WHO functional class II-III as assessed by the screening clinician. * Clinically stable patients on pulmonary vasodilator treatment with PDE5i, ERA, PA/IPA alone or in combination without considerations from the treating physician team towards treatment escalation and a treatment duration of at least four weeks. Clinical stability defined as stable symptoms without progression as assessed by treating clinician and without the need for unplanned hospital admissions due to worsening PAH within three months of screening. * Fertile women (\< 50 years of age) must use safe contraceptives (Intra uterine device or hormonal contraception) for the duration of the study and have a negative pregnancy test * Able to understand the written patient information in Danish and give informed consent. * Age ≥ 18 years * Ability to perform cardio pulmonary exercise test
Exclusion criteria
* Known allergy to the study medication * Treatment with an SGLT2i within 6 months prior to baseline * Type 1 or type 2 diabetes * Impaired renal function with an eGFR \< 30 mL/min/m2 within four weeks of screening * Severe liver dysfunction (Child-Pugh class c) * Listed for lung transplantation at the time of screening * Planned initiation of iv prostacyclin therapy/ IPA or current dose escalation planned * Planned pulmonary endarterectomy or pulmonary balloon angioplasty. * LVEF \< 50% * Diagnosis of PAH group 2, 3 or 5
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in VO2 max from baseline to follow up | 3 months |
Secondary
| Measure | Time frame |
|---|---|
| Change in 6 minutes walking distance | 3 months |
| Change in VE/VCO2 | 3 months |
| Change in pulmonary vascular resistance | 3 months |
| Change in mean pulmonary artery pressure | 3 months |
| Change in Cardiac index | 3 months |
| Change in central venous pressure | 3 months |
| Change in transpulmonary gradient | 3 months |
| Change in pulmonary arterial compliance | 3 months |
| Change in right ventricular size on 3D echocardiography | 3 months |
| Change in right ventricular free wall strain | 3 months |
| Change in right ventricular free wall strain-work (free wall strain/ pulmonary artery pressure) | 3 months |
| Change in NTproBNP | 3 months |
| Change in EQ-5D-5L questionnaire | 3 months |
| Change in metabolomic pattern on central venous blood | 3 months |
Countries
Denmark
Outcome results
None listed