Dapagliflozin in Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension Clinical Trial

— DAPAH  

Official title:

Effects of DAPAgliflozin on Cardiopulmonary Exercise Capacity and Hemodynamics in Pulmonary Arterial Hypertension: A Double Blind Randomized Trial. (DAPAH-trial)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05179356
• Other study ID #: DAPAH16122021
• Status: Recruiting
• Phase: Phase 2
• Start date: January 1, 2023
• Est. completion date: September 2024

Study information

• Verified date: December 2023
• Source: Rigshospitalet, Denmark
• Contact: Mads Ersbøll, MD, PhD
• Phone: +45 35453580
• Email: mads.kristian.ersboell.02[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Recruiting
• Enrollment: 52
• Est. completion date: September 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Thromboembolic Pulmonary Hypertension
• Familial Primary Pulmonary Hypertension
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Dapagliflozin 10 MG [Farxiga]
Dapagliflozin 10 mg given once daily for three months
• Placebo
Matching placebo

Locations

Country	Name	City	State
Denmark	Rigshospitalet	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Mads Ersbøll

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in VO2 max from baseline to follow up		3 months
Secondary	Change in 6 minutes walking distance		3 months
Secondary	Change in VE/VCO2		3 months
Secondary	Change in pulmonary vascular resistance		3 months
Secondary	Change in mean pulmonary artery pressure		3 months
Secondary	Change in Cardiac index		3 months
Secondary	Change in central venous pressure		3 months
Secondary	Change in transpulmonary gradient		3 months
Secondary	Change in pulmonary arterial compliance		3 months
Secondary	Change in right ventricular size on 3D echocardiography		3 months
Secondary	Change in right ventricular free wall strain		3 months
Secondary	Change in right ventricular free wall strain-work (free wall strain/ pulmonary artery pressure)		3 months
Secondary	Change in NTproBNP		3 months
Secondary	Change in EQ-5D-5L questionnaire		3 months
Secondary	Change in metabolomic pattern on central venous blood		3 months