Dapagliflozin in Pulmonary Arterial Hypertension (DAPAH)

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

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

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Arterial Hypertension; Chronic Thromboembolic Pulmonary Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: Dapagliflozin 10 MG [Farxiga]

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.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mads Ersbøll, MD, PhD; Phone Number: +45 35453580; Email: mads.kristian.ersboell.02@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet
    • Contact: Mads Ersbøll, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dapagliflozin 10 mg once daily; Dapagliflozin 10 mg (Farxiga 10 mg) given once daily for three months	Drug: Dapagliflozin 10 MG [Farxiga]; Dapagliflozin 10 mg given once daily for three months
Placebo Comparator: Matching placebo; Placebo given once daily for three months	Drug: Placebo; Matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in VO2 max from baseline to follow up	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in 6 minutes walking distance	3 months
Change in VE/VCO2	3 months
Change in pulmonary vascular resistance	3 months
Change in mean pulmonary artery pressure	3 months
Change in Cardiac index	3 months
Change in central venous pressure	3 months
Change in transpulmonary gradient	3 months
Change in pulmonary arterial compliance	3 months
Change in right ventricular size on 3D echocardiography	3 months
Change in right ventricular free wall strain	3 months
Change in right ventricular free wall strain-work (free wall strain/ pulmonary artery pressure)	3 months
Change in NTproBNP	3 months
Change in EQ-5D-5L questionnaire	3 months
Change in metabolomic pattern on central venous blood	3 months

Collaborators and Investigators

• Sponsor: Mads Ersbøll

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: December 16, 2021
• First Submitted That Met QC Criteria: December 16, 2021
• First Posted (Actual): January 5, 2022

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension, Pulmonary; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: DAPAH16122021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No