Dapagliflozin in Pulmonary Arterial Hypertension (DAPAH)
- Conditions
- Chronic thromboembolic pulmonary hypertensionPulmonary arterial hypertension
- Registration Number
- 2024-518551-37-00
- Lead Sponsor
- Rigshospitalet
- Brief Summary
The objective of this study is to evaluate the effects of oral dapagliflozin (Forxiga®) treatment versus placebo in clinically stable patients with PAH on background vasodilator combination therapy on cardiopulmonary exercise capacity, pulmonary vascular hemodynamics, RV function and metabolomic profile of the pulmonary vascular endothelium.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruiting
- Sex
- Not specified
- Target Recruitment
- 52
A diagnosis of PAH group 4 or group 1 in any of the following subtypes: 1) Idiopathic PAH (iPAH), 2) Heritable PAH (hPAH), 3) Connective tissue disease associated PAH (aPAH). In case of PAH 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
Known allergy to the study medication
Diagnosis of PAH group 2, 3 or 5
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%
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Change in maximum oxygen consumption (VO2 max) measured by cardiopulmonary exercise testing from baseline to follow up after ninety days between dapagliflozin and placebo Change in maximum oxygen consumption (VO2 max) measured by cardiopulmonary exercise testing from baseline to follow up after ninety days between dapagliflozin and placebo
- Secondary Outcome Measures
Name Time Method Change in mean pulmonary artery pressure (meanPAP) from baseline to follow up after ninety days Change in mean pulmonary artery pressure (meanPAP) from baseline to follow up after ninety days
Change in 6-minute walking distance (6MWD) from baseline to follow up after three months Change in 6-minute walking distance (6MWD) from baseline to follow up after three months
Change in VE/VCO2 from baseline to follow up after ninety days Change in VE/VCO2 from baseline to follow up after ninety days
Change in cardiac index (CI) and pulmonary vascular resistance (PVR) from baseline to follow up after ninety days Change in cardiac index (CI) and pulmonary vascular resistance (PVR) from baseline to follow up after ninety days
Change in central venous pressure (CVP) from baseline to follow up after ninety days Change in central venous pressure (CVP) from baseline to follow up after ninety days
Change in transpulmonary gradient from baseline to follow up after ninety days Change in transpulmonary gradient from baseline to follow up after ninety days
Change in pulmonary arterial compliance (sysPAP/strokevolume) from baseline to follow up after ninety days Change in pulmonary arterial compliance (sysPAP/strokevolume) from baseline to follow up after ninety days
Change in right ventricular (RV) size as assessed by 3D echocardiography from baseline to follow up after ninety days Change in right ventricular (RV) size as assessed by 3D echocardiography from baseline to follow up after ninety days
Change in right ventricular (RV) free wall strain from baseline to follow up after three months Change in right ventricular (RV) free wall strain from baseline to follow up after three months
Change in right ventricular (RV) free wall strain-work (RV-LS / meanPAP) from baseline to follow up after ninety days Change in right ventricular (RV) free wall strain-work (RV-LS / meanPAP) from baseline to follow up after ninety days
Change in plasma NT-proBNP from baseline to follow up after ninety days Change in plasma NT-proBNP from baseline to follow up after ninety days
Change in EQ-5D-5L questionnaire from baseline to follow up after ninety days Change in EQ-5D-5L questionnaire from baseline to follow up after ninety days
Change in metabolomic and proteomic patterns from baseline to follow up after three months Change in metabolomic and proteomic patterns from baseline to follow up after three months
Changes in selected biomarkers, se section on biomarkers from baseline to follow up after ninety days Changes in selected biomarkers, se section on biomarkers from baseline to follow up after ninety days
Trial Locations
- Locations (1)
Rigshospitalet
🇩🇰Copenhagen Oe, Denmark
Rigshospitalet🇩🇰Copenhagen Oe, DenmarkMads ErsbøllSite contact35453580mads.kristian.ersboell.02@regionh.dk