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Dapagliflozin in Pulmonary Arterial Hypertension

Phase 2
Recruiting
Conditions
Chronic Thromboembolic Pulmonary Hypertension
Pulmonary Arterial Hypertension
Interventions
Registration Number
NCT05179356
Lead Sponsor
Mads Ersbøll
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
52
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

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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Dapagliflozin 10 mg once dailyDapagliflozin 10 MG [Farxiga]Dapagliflozin 10 mg (Farxiga 10 mg) given once daily for three months
Matching placeboPlaceboPlacebo given once daily for three months
Primary Outcome Measures
NameTimeMethod
Change in VO2 max from baseline to follow up3 months
Secondary Outcome Measures
NameTimeMethod
Change in NTproBNP3 months
Change in right ventricular size on 3D echocardiography3 months
Change in 6 minutes walking distance3 months
Change in Cardiac index3 months
Change in right ventricular free wall strain3 months
Change in right ventricular free wall strain-work (free wall strain/ pulmonary artery pressure)3 months
Change in VE/VCO23 months
Change in pulmonary vascular resistance3 months
Change in metabolomic pattern on central venous blood3 months
Change in mean pulmonary artery pressure3 months
Change in central venous pressure3 months
Change in transpulmonary gradient3 months
Change in pulmonary arterial compliance3 months
Change in EQ-5D-5L questionnaire3 months

Trial Locations

Locations (1)

Rigshospitalet

🇩🇰

Copenhagen, Denmark

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