Dapagliflozin in Pulmonary Arterial Hypertension (DAPAH)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rigshospitalet

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

1 Jan 2023 → 13 Jan 2026

Decision date (initial)

2024-10-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-518551-37-00

EudraCT number

2021-006787-25

ClinicalTrials.gov

NCT05179356

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The objective of this study is to evaluate the effects of oral dapagliflozin (Forxiga®) treatment versus placebo in clinically stable patients with PAH on background vasodilator combination therapy on cardiopulmonary exercise capacity, pulmonary vascular hemodynamics, RV function and metabolomic profile of the pulmonary vascular endothelium.

Conditions and MedDRA coding

Chronic thromboembolic pulmonary hypertension

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. A diagnosis of PAH group 4 or group 1 in any of the following subtypes: 1) Idiopathic PAH (iPAH), 2) Heritable PAH (hPAH), 3) Connective tissue disease associated PAH (aPAH). In case of PAH in group 4, no further invasive treatment including pulmonary endarterectomy or pulmonary balloon angioplasty must be planned at time of inclusion.
2. Symptomatic PAH in WHO functional class II-III as assessed by the screening clinician.
3. 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.
4. 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
5. Able to understand the written patient information in Danish and give informed consent.
6. Age ≥ 18 years
7. Ability to perform cardio pulmonary exercise test

Exclusion criteria 10

1. Known allergy to the study medication
2. Treatment with an SGLT2i within 6 months prior to baseline
3. Type 1 or type 2 diabetes
4. Impaired renal function with an eGFR < 30 mL/min/m2 within four weeks of screening
5. Severe liver dysfunction (Child-Pugh class c)
6. Listed for lung transplantation at the time of screening
7. Planned initiation of iv prostacyclin therapy/ IPA or current dose escalation planned
8. Planned pulmonary endarterectomy or pulmonary balloon angioplasty.
9. LVEF < 50%
10. Diagnosis of PAH group 2, 3 or 5

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in maximum oxygen consumption (VO2 max) measured by cardiopulmonary exercise testing from baseline to follow up after ninety days between dapagliflozin and placebo

Secondary endpoints 14

1. Change in 6-minute walking distance (6MWD) from baseline to follow up after three months
2. Change in VE/VCO2 from baseline to follow up after ninety days
3. Change in mean pulmonary artery pressure (meanPAP) from baseline to follow up after ninety days
4. Change in cardiac index (CI) and pulmonary vascular resistance (PVR) from baseline to follow up after ninety days
5. Change in central venous pressure (CVP) from baseline to follow up after ninety days
6. Change in transpulmonary gradient from baseline to follow up after ninety days
7. Change in pulmonary arterial compliance (sysPAP/strokevolume) from baseline to follow up after ninety days
8. Change in right ventricular (RV) size as assessed by 3D echocardiography from baseline to follow up after ninety days
9. Change in right ventricular (RV) free wall strain from baseline to follow up after three months
10. Change in right ventricular (RV) free wall strain-work (RV-LS / meanPAP) from baseline to follow up after ninety days
11. Change in plasma NT-proBNP from baseline to follow up after ninety days
12. Change in EQ-5D-5L questionnaire from baseline to follow up after ninety days
13. Change in metabolomic and proteomic patterns from baseline to follow up after three months
14. Changes in selected biomarkers, se section on biomarkers from baseline to follow up after ninety days

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rigshospitalet

Sponsor organisation

Rigshospitalet

Address

Blegdamsvej 9

City

Copenhagen Oe

Postcode

2100

Country

Denmark

Scientific contact point

Organisation

Rigshospitalet

Contact name

Mads Ersbøll

Public contact point

Organisation

Rigshospitalet

Contact name

Mads Ersbøll

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications