Pulmonary arterial hypertension Chronic thromboembolic pulmonary hypertension MedDRA version: 21.1 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 20.0 Level: LLT Classification code 10065150 Term: Associated with pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 21.1 Level: LLT Classification c
Conditions
Interventions
Trade Name: Forxiga (dapagliflozin)
Product Name: Forxiga
Pharmaceutical Form: Tablet
INN or Proposed INN: Dapagliflozin
CAS Number: 461432-26-8
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
Rigshospitalet The Heart Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • A diagnosis of PAH group 4 or group 1 in any of the following subtypes: o Idiopathic PAH (iPAH) o Heritable PAH (hPAH) o Connective tissue disease associated PAH (aPAH) o 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 (=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
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 |
|---|---|
| Main Objective: 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 cardio-pulmonary exercise capacity, pulmonary vascular hemodynamics, RV function and metabolomic profile of the pulmonary vascular endothelium.;Secondary Objective: Not applicable;Primary end point(s): Change in maximum oxygen consumption (VO2 max) measured by cardiopulmonary exercise testing from baseline to follow up after ninety days between dapagliflozin and placebo.;Timepoint(s) of evaluation of this end point: 3 months / 90 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • 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 mean pulmonary artery pressure (meanPAP) 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 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 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-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 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 • Changes in selected biomarkers, se section on biomarkers from baseline to follow up after ninety days ;Timepoint(s) of evaluation of this end point: 3 months / 90 days | — |
Countries
Denmark
Contacts
Public ContactMads Ersbøll
Rigshospitalet The Heart Center
Outcome results
None listed