Dapagliflozin in Pulmonary Arterial Hypertension (DAPAH)

Mads Ersbøll

Status and phase: Enrolling; Phase 2

Conditions: Chronic Thromboembolic Pulmonary Hypertension; Pulmonary Arterial Hypertension

Treatments: Drug: Placebo; Drug: Dapagliflozin 10 MG [Farxiga]

Study type: Interventional

Funder types: Other

Identifiers

NCT05179356

DAPAH16122021

Details and patient eligibility

About

The purpose of this study is to investigate the effects of dapagliflozin on exercise capacity and hemodynamics in patients with pulmonary arterial hypertension

Full 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.

Enrollment: 52 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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52 participants in 2 patient groups, including a placebo group

Dapagliflozin 10 mg once daily

Active Comparator group

Description:

Dapagliflozin 10 mg (Farxiga 10 mg) given once daily for three months

Treatment:

Drug: Dapagliflozin 10 MG [Farxiga]

Matching placebo

Placebo Comparator group

Description:

Placebo given once daily for three months

Treatment:

Drug: Placebo