Idiopathic Pulmonary Arterial HypertensionPhase 2Emphower PoCNCT05493371
Empagliflozin in Pulmonary Arterial Hypertension
A Phase 2 study testing Empagliflozin 10 MG in people with Idiopathic Pulmonary Arterial Hypertension, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
The aim of the study is to determine whether conducting a randomized placebo-controlled clinical trial is feasible, safe for the patient and whether the treatment is well tolerated in patients with idiopathic pulmonary arterial hypertension. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Idiopathic Pulmonary Arterial Hypertension
- What is being tested?
- Empagliflozin 10 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Mar 2023to 1 Nov 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Diagnosis of idiopathic PAH
- Documented diagnostic right heart catheterization (RHC) at any time prior to screening confirming diagnosis of WHO diagnostic pulmonary hypertension Group I: PAH with subtype idiopathic PAH. The documented RHC shows all of the following criteria:
- mPAP > 20 mmHg at rest
- Pulmonary artery wedge pressure (PAWP) or left ventricular end-diastolic pressure (LVEDP) ≤ 15 mmHg at rest
- PVR ≥ 240 dyn·sec/cm5 (3 Wood units) at rest
- Symptomatic pulmonary hypertension classified as World Health Organization (WHO) functional class (FC) II, III or IV
- PAH therapy is at stable (per investigator) dose levels of standard of care (SoC) therapies for at least 90 days prior screening. SoC therapy refers to a therapy consisting of at least 1 agent from a list including: an endothelin-receptor antagonist (ERA), a phosphodiesterase 5 (PDE5) inhibitor, a soluble guanylate cyclase stimulator, and/or a prostacyclin analogue or receptor agonist (SC/inhaled/PO).
Who cannot join
- Any subject who received any investigational medication within 1 month prior to the start of this study or who is scheduled to receive another investigational drug during the course of this study. Patients participating in a purely observational trial will not be excluded
- Females of childbearing potential, defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 months), unable or unwillingly to either:
- Use highly effective methods of birth control according to the International Conference on harmonisation of pharmaceuticals for human use (ICH) that result in a low failure rate of less than 1% per year when used consistently and correctly 43. Highly effective methods include hormonal contraception (for example, birth control pills, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation (having your tubes tied); or a partner with a vasectomy who has completed follow-up to confirm a successful procedure
- Have a negative pregnancy tests as verified by the investigator prior to starting study therapy and agrees to have an extra pregnancy test 8 weeks after start of the study
- Contraindication for CMR imaging as defined in the protocol of the Amsterdam UMC "Kwaliteitsdocument Cardiale MRI (Versie 1)". The list of contra-indications includes: claustrophobia, ferromagnetic implants, implanted cardioverter defibrillator (ICD) or pacemaker (except for the MR conditional) and ball-in-cage mechanic heart valve.
- Impaired renal function, defined as eGFR < 30 mL/min/1.73 m2 (CKD-EPI) or requiring dialysis
Show all 23Show fewer
- History of chronic severe (Child Pugh classification score >10, Appendix 1) or active liver disease defined as serums transaminases >5 x upper limit of normal (ULN) or bilirubin > 1.5 x ULN
- History of ketoacidosis
- Known allergy, intolerance or hypersensitivity to empagliflozin or other SGLT-2 inhibitors
- Use of lithium compounds and being unable or unwillingly to increase the monitoring frequency of lithium levels
- Current or scheduled use of the following Uridine glucuronosyltransferase (UGT) inducers: phenytoin, rifampicin, carbamazepine, lamotrigine, ritonavir, efavirenz, tipranavir, phenobarbital, testosterone propionate and nelfinavir.
- Current or prior use of a SGLT-2 inhibitor
- Heart transplant recipient or listed for heart transplant
- Chronic pulmonary disease requiring home oxygen or steroid maintenance therapy
- Symptomatic hypotension and/or a systolic blood pressure (SBP) < 90 mmHg at screening
- Gastrointestinal (GI) surgery or GI disorder that could interfere with absorption of trial medication in the investigator's opinion
- Presence of any other disease than pulmonary arterial hypertension with a life expectancy of <1 year in the investigator's opinion
- Women who are pregnant, nursing, or who plan to become pregnant while in the trial
- History of severe (previously required or prolonged patient hospitalization, resulted in persistent or marked disability/incapacity) or recurrent (≥2 infections in six months or ≥3 infections in one year) genital infections.
- History of severe hypoglycaemia (<40 - 30 mg/dL = <2.2 - 1.7 mmol/L), previous hospitalisation for hypoglycaemia or seizures attributed to hypoglycaemia
- Active solid or haematological malignancy, with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or ≤ 2 squamous cell carcinomas of the skin
- History or suspicion of inability to cooperate adequately
- Any condition that, in the investigator's opinion, makes them an unreliable trial subject or unlikely to complete the trial
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Amsterdam UMC, location Vumc
Amsterdam, North Holland, 1081 HV
About this study
Official title: Feasibility Study of Empagliflozin As Treatment for Idiopathic Pulmonary Arterial Hypertension
The aim of the study is to determine whether conducting a randomized placebo-controlled clinical trial is feasible, safe for the patient and whether the treatment is well tolerated in patients with idiopathic pulmonary arterial hypertension.
Read the detailed description
This study is designed as a prospective, single-center, phase IIa, single-arm, open-label, interventional proof-of-concept trial in patients diagnosed with idiopathic pulmonary arterial hypertension (IPAH) who are currently on stable therapy. Patients will be administered a once-daily oral dose of 10 mg empagliflozin for a duration of 12 weeks along with standard treatment. The primary objective of this study is to assess safety and tolerability of empagliflozin and to assess whether a potential future randomized, double-blind, placebo-controlled study is feasible.
- Being tested
- Empagliflozin 10 MG
- Keywords
- Empagliflozin
- Medical subject headings
- Familial Primary Pulmonary Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 10 MGDrug
10 mg once daily empagliflozin oral tablets for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin | Experimental | Not described Receives: Drug: Empagliflozin 10 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tolerability: the number of patients who have to prematurely discontinue treatment due to intolerability or adverse events.
Measured: 12 weeks
Feasibility: time needed to include all patients and number of patients needed to screen.
Measured: 12 weeks
Safety: the number of adverse events (AEs), severe adverse events (SAEs), adverse event of special interest (AESI) and suspected unexpected serious adverse reactions (SUSARs).
Measured: 12 weeks
Secondary outcomes (14)
Right ventricle ejection fraction (RVEF) measured using MRI
RVEF is calculated using the RVESV, RVEDV
Measured: 12 weeks
Right ventricle mass measured using MRI
Measured: 12 weeks
Left ventricle ejection fraction (LVEF) measured using MRI
LVEF is calculated using the LVESV, LVEDV
Measured: 12 weeks
Stroke volume (SV) measured using MRI
SV is calculated using the LVESV, LVEDV
Measured: 12 weeks
Tricuspid annular plane systolic excursion (TAPSE) measured using transthoracic ultrasound
Measured: 12 weeks
Estimated sPAP measured using transthoracic ultrasound
Measured: 12 weeks
Right ventricle fractional area change (RVFAC) measured using transthoracic ultrasound
Measured: 12 weeks
Blood biomarkers
Endpoints: Expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and bone morphogenetic protein receptor II (BMPR2) in peripheral blood mononuclear cells (PMBC)
Measured: 12 weeks
Blood safety biomarkers
Fasting glucose, N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP) and creatinine in blood.
Measured: 12 weeks
Urine safety biomarkers
Ketones, nitrites, leukocytes and glucose in urine test strip (dipstick).
Measured: 12 weeks
Functional class
World Health Organization Function Classification of Pulmonary Hypertension. Outcome: Class I, Class II, Class III or Class IV
Measured: 12 weeks
Six-Minute Walk Distance
Six-minute walk distance (6MWD) will be measured by the 6-minute walk test (6MWT). The test should preferably be conducted on a straight 30 metre track. The patient is instructed to walk as far as possible for six minutes. One lap is demonstrated. The patient is told that slowing down can be necessary, and after pausing are encouraged to start walking as soon as possible.
Measured: 12 weeks
Quality of life measured with use of the EMPHASIS-10 questionnaire
The emPHasis-10 is a short questionnaire for assessing Health-related quality of life in pulmonary arterial hypertension. The questionnaire comprises 10 items that are formatted as a semantic six-point differential scale and results in a score out of 50 where a higher score represents a higher symptom burden.
Measured: 12 weeks
Quality of life measured with use of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) questionnaire
The CAMPHOR questionnaire contains 65 items in total. The measure consists of three different scales: a symptom scale assessing energy, breathlessness and mood (25-items; low score indicating minimal symptoms); activity limitations scale with a 3-point rating system (15-items; range 0 to 30, lower score indicating minimal activity limitation); and a QoL scale (25-items; lower score indicating better QoL). It is negatively weighted; a higher score indicates worse QoL and greater functional limitation.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2022
- Study start1 Mar 2023
- Primary completion1 Nov 2024
- Study completion1 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- prospective single-center, phase IIa, single arm, open label, interventional proof-of-concept study
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Harm Jan Bogaard, VU University of Amsterdam
- Investigators
- Harm Jan Bogaard, Prof. dr., Principal investigator, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05493371
- Sponsor's protocol ID
- 81866
- Other IDs
- 2022-002400-20, 2022-501512-33-00
- Acronym
- Emphower PoC
- Status last verified
- Nov 2024
- First submitted
- 28 Jul 2022
- Last updated
- 20 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: On reasonable request
Publications
Yoshida K, Toth E, Duijvelaar E, Neep B, Agarwal S, Pan X, Sanada T, Yoshida Y, Aman J, de Jesus Perez VA, Handoko ML, de Man FS, Sun XQ, Bogaard HJ. Empagliflozin Ameliorates Experimental Pulmonary Vascular Remodeling, but May Not Benefit Patients With Pulmonary Arterial Hypertension. J Am Heart Assoc. 2026 Aug 4;15(15):e047945. doi: 10.1161/JAHA.125.047945. Epub 2026 Jul 25.
PubMed 42500881
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility Study of Empagliflozin As Treatment for Idiopathic Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT05493371
- Acronym / sponsor ID
- Emphower PoC / 81866
- Keywords
- Empagliflozin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- 1 Mar 2023 (actual)
- Primary completion
- 1 Nov 2024 (actual)
- Study completion
- 1 Nov 2024 (actual)
- First posted
- 9 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to determine whether conducting a randomized placebo-controlled clinical trial is feasible, safe for the patient and whether the treatment is well tolerated in patients with idiopathic pulmonary arterial hypertension.
Detailed description
This study is designed as a prospective, single-center, phase IIa, single-arm, open-label, interventional proof-of-concept trial in patients diagnosed with idiopathic pulmonary arterial hypertension (IPAH) who are currently on stable therapy. Patients will be administered a once-daily oral dose of 10 mg empagliflozin for a duration of 12 weeks along with standard treatment. The primary objective of this study is to assess safety and tolerability of empagliflozin and to assess whether a potential future randomized, double-blind, placebo-controlled study is feasible.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- prospective single-center, phase IIa, single arm, open label, interventional proof-of-concept study
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin | Experimental | Drug: Empagliflozin 10 MG |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 18 years
- Diagnosis of idiopathic PAH
- Documented diagnostic right heart catheterization (RHC) at any time prior to screening confirming diagnosis of WHO diagnostic pulmonary hypertension Group I: PAH with subtype idiopathic PAH. The documented RHC shows all of the following criteria:
- Symptomatic pulmonary hypertension classified as World Health Organization (WHO) functional class (FC) II, III or IV
- PAH therapy is at stable (per investigator) dose levels of standard of care (SoC) therapies for at least 90 days prior screening. SoC therapy refers to a therapy consisting of at least 1 agent from a list including: an endothelin-receptor antagonist (ERA), a phosphodiesterase 5 (PDE5) inhibitor, a soluble guanylate cyclase stimulator, and/or a prostacyclin analogue or receptor agonist (SC/inhaled/PO).
Key exclusion criteria (23 listed)
- Any subject who received any investigational medication within 1 month prior to the start of this study or who is scheduled to receive another investigational drug during the course of this study. Patients participating in a purely observational trial will not be excluded
- Females of childbearing potential, defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 months), unable or unwillingly to either:
- Contraindication for CMR imaging as defined in the protocol of the Amsterdam UMC "Kwaliteitsdocument Cardiale MRI (Versie 1)". The list of contra-indications includes: claustrophobia, ferromagnetic implants, implanted cardioverter defibrillator (ICD) or pacemaker (except for the MR conditional) and ball-in-cage mechanic heart valve.
- Impaired renal function, defined as eGFR < 30 mL/min/1.73 m2 (CKD-EPI) or requiring dialysis
- History of chronic severe (Child Pugh classification score >10, Appendix 1) or active liver disease defined as serums transaminases >5 x upper limit of normal (ULN) or bilirubin > 1.5 x ULN
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Empagliflozin 10 MG10 mg once daily empagliflozin oral tablets for 12 weeks | Drug | Empagliflozin |
Primary outcome
Tolerability: the number of patients who have to prematurely discontinue treatment due to intolerability or adverse events.
Time frame: 12 weeks
Feasibility: time needed to include all patients and number of patients needed to screen.
Time frame: 12 weeks
Safety: the number of adverse events (AEs), severe adverse events (SAEs), adverse event of special interest (AESI) and suspected unexpected serious adverse reactions (SUSARs).
Time frame: 12 weeks
14 secondary outcomes
Right ventricle ejection fraction (RVEF) measured using MRI
Time frame: 12 weeks
Right ventricle mass measured using MRI
Time frame: 12 weeks
Left ventricle ejection fraction (LVEF) measured using MRI
Time frame: 12 weeks
Stroke volume (SV) measured using MRI
Time frame: 12 weeks
Tricuspid annular plane systolic excursion (TAPSE) measured using transthoracic ultrasound
Time frame: 12 weeks
Estimated sPAP measured using transthoracic ultrasound
Time frame: 12 weeks
Right ventricle fractional area change (RVFAC) measured using transthoracic ultrasound
Time frame: 12 weeks
Blood biomarkers
Time frame: 12 weeks
Blood safety biomarkers
Time frame: 12 weeks
Urine safety biomarkers
Time frame: 12 weeks
Functional class
Time frame: 12 weeks
Six-Minute Walk Distance
Time frame: 12 weeks
Quality of life measured with use of the EMPHASIS-10 questionnaire
Time frame: 12 weeks
Quality of life measured with use of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) questionnaire
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2024.
- Derived from this study: PubMed 42500881Yoshida K, Toth E, Duijvelaar E, Neep B, Agarwal S, Pan X, Sanada T, Yoshida Y, Aman J, de Jesus Perez VA, Handoko ML, de Man FS, Sun XQ, Bogaard HJ. Empagliflozin Ameliorates Experimental Pulmonary Vascular Remodeling, but May Not Benefit Patients With Pulmonary Arterial Hypertension. J Am Heart Assoc. 2026 Aug 4;15(15):e047945. doi: 10.1161/JAHA.125.047945. Epub 2026 Jul 25.
- Individual participant dataSharing planned: Yes. On reasonable request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Harm Jan Bogaard, Prof. dr. principal investigator
Amsterdam UMC, location VUmc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Empagliflozin 10 MG in people with Idiopathic Pulmonary Arterial Hypertension, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tolerability: the number of patients who have to prematurely discontinue treatment due to intolerability or adverse events. (time frame: 12 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05493371, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2024.