The effects of dapagliflozin in patients with elevated blood pressure in the lungs

Phase 1

• Conditions: Pulmonary arterial hypertensionChronic thromboembolic pulmonary hypertension; MedDRA version: 21.1Level: PTClassification code 10064911Term: Pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; MedDRA version: 20.0Level: LLTClassification code 10065150Term: Associated with pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; MedDRA version: 21.1Level: LLTClassification code 10065151Term: Idiopathic pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; MedDRA version: 24.1Level: PTClassification code 10085244Term: Heritable pulmonary arterial hypertensionSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; MedDRA version: 21.0Level: LLTClassification code 10068740Term: CTEPHSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2021-006787-25-DK
• Lead Sponsor: Rigshospitalet The Heart Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-12-22
• Last Update Posted: 8 August 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

•A diagnosis of PAH group 4 or group 1 in any of the following subtypes:
oIdiopathic PAH (iPAH)
oHeritable PAH (hPAH)
oConnective tissue disease associated PAH (aPAH)
oIn 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 42
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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