Clinical trial NCT05179356: Dapagliflozin in Pulmonary Arterial Hypertension
Official title: Effects of DAPAgliflozin on Cardiopulmonary Exercise Capacity and Hemodynamics in Pulmonary Arterial Hypertension: A Double Blind Randomized Trial. (DAPAH-trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pulmonary Arterial Hypertension
Chronic Thromboembolic Pulmonary Hypertension
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2022-01-05
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in VO2 max from baseline to follow up
timeFrame: 3 months
Secondary outcomes:
measure: Change in 6 minutes walking distance
timeFrame: 3 months
measure: Change in VE/VCO2
timeFrame: 3 months
measure: Change in pulmonary vascular resistance
timeFrame: 3 months
measure: Change in mean pulmonary artery pressure
timeFrame: 3 months
measure: Change in Cardiac index
timeFrame: 3 months
measure: Change in central venous pressure
timeFrame: 3 months
measure: Change in transpulmonary gradient
timeFrame: 3 months
measure: Change in pulmonary arterial compliance
timeFrame: 3 months
measure: Change in right ventricular size on 3D echocardiography
timeFrame: 3 months
measure: Change in right ventricular free wall strain
timeFrame: 3 months
measure: Change in right ventricular free wall strain-work (free wall strain/ pulmonary artery pressure)
timeFrame: 3 months
measure: Change in NTproBNP
timeFrame: 3 months
measure: Change in EQ-5D-5L questionnaire
timeFrame: 3 months
measure: Change in metabolomic pattern on central venous blood
timeFrame: 3 months
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
Study officials:
References: