Feasibility Study of Empagliflozin As Treatment for Idiopathic Pulmonary Arterial Hypertension

Amsterdam UMC, location VUmc1 site in 1 country8 target enrollmentMarch 1, 2023

ConditionsIdiopathic Pulmonary Arterial Hypertension

InterventionsEmpagliflozin 10 MG

DrugsEmpagliflozin 10 MG

Overview

Phase: Phase 2
Intervention: Empagliflozin 10 MG
Conditions: Idiopathic Pulmonary Arterial Hypertension
Sponsor: Amsterdam UMC, location VUmc
Enrollment: 8
Locations: 1
Primary Endpoint: Tolerability: the number of patients who have to prematurely discontinue treatment due to intolerability or adverse events.
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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.

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.

Registry

clinicaltrials.gov

Start Date

March 1, 2023

End Date

November 1, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Amsterdam UMC, location VUmc

Responsible Party

Principal Investigator

Harm Jan Bogaard

Prof. Dr.

VU University of Amsterdam

Eligibility Criteria

Inclusion Criteria

•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).

Exclusion Criteria

•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
•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
•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

Arms & Interventions

Empagliflozin

Intervention: Empagliflozin 10 MG

Outcomes

Primary Outcomes

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

Secondary Outcomes

Estimated sPAP measured using transthoracic ultrasound(12 weeks)
Right ventricle mass measured using MRI(12 weeks)
Right ventricle ejection fraction (RVEF) measured using MRI(12 weeks)
Stroke volume (SV) measured using MRI(12 weeks)
Right ventricle fractional area change (RVFAC) measured using transthoracic ultrasound(12 weeks)
Urine safety biomarkers(12 weeks)
Blood biomarkers(12 weeks)
Functional class(12 weeks)
Six-Minute Walk Distance(12 weeks)
Left ventricle ejection fraction (LVEF) measured using MRI(12 weeks)
Tricuspid annular plane systolic excursion (TAPSE) measured using transthoracic ultrasound(12 weeks)
Quality of life measured with use of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) questionnaire(12 weeks)
Blood safety biomarkers(12 weeks)
Quality of life measured with use of the EMPHASIS-10 questionnaire(12 weeks)