Feasibility of empagliflozin as treatment for idiopathic pulmonary arterial hypertensio

Phase 2

• Conditions: 10037454; Idiopathic Pulmonary Arterial Hypertension; increased pulmonary artery pressure of unknown cause

• Registration Number: NL-OMON51825
• Lead Sponsor: Amsterdam UMC, locatie VUmc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 9 April 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 8

Inclusion Criteria

1. Age >= 18 years
2. Diagnosis of idiopathic PAH
3. 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:
a. mPAP > 20 mmHg at rest
b. Pulmonary artery wedge pressure (PAWP) or left ventricular end-diastolic
pressure (LVEDP) <= 15 mmHg at rest
c. PVR >= 240 dyn·sec/cm5 (3 Wood units) at rest
4. Symptomatic pulmonary hypertension classified as World Health Organization
(WHO) functional class (FC) II, III or IV
5. 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).

Exclusion Criteria

1. 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
2. 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:
a. 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
b. 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
3. 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.
4. Impaired renal function, defined as eGFR < 30 mL/min/1.73 m2 (CKD-EPI) or
requiring dialysis
5. 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
6. History of ketoacidosis
7. Known allergy, intolerance or hypersensitivity to empagliflozin or other
SGLT-2 inhibitors
8. Use of lithium compounds and being unable or unwillingly to increase the
monitoring frequency of lithium levels
9. Current or scheduled use of the following Uridine glucuronosyltransferase
(UGT) inducers: phenytoin, rifampicin, carbamazepine, lamotrigine, ritonavir,
efavirenz, tipranavir, phenobarbital, testosterone propionate and nelfinavir.
10. Current or prior use of a SGLT-2 inhibitor
11. Heart transplant recipient or listed for heart transplant
12. Chronic pulmonary disease requiring home oxygen or steroid maintenance
therapy
13. Symptomatic hypotension and/or a systolic blood pressure (SBP) < 90 mmHg at
screening
14. Gastrointestinal (GI) surgery or GI disorder that could interfere with
absorption of trial medication in the investigator*s opinion
15. Presence of any other disease than pulmonary arterial hypertension with a
life expectancy of <1 year in the investigator*s opinion
16. Women who are pregnant, nursing, or who plan to become pregnant while in
the trial
17. History of severe (previously required or prolonged patient
hospitalization, resulted in persistent or marked disability/incapacity) or
recurrent (>=2 infections in si

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The main study objectives and endpoints of this trial are to determine during a<br /><br>follow up of 12 weeks:<br /><br>• Tolerability. Endpoints: the number of patients who have to prematurely<br /><br>discontinue treatment due to intolerability or adverse events.<br /><br>• Feasibility: Endpoints: time needed to include all patients and number of<br /><br>patients needed to screen.<br /><br>• Safety. Endpoints: the number of adverse events (AEs), severe adverse events<br /><br>(SAEs), adverse event of special interest (AESI) and suspected unexpected<br /><br>serious adverse reactions (SUSARs).</p><br>