Empagliflozin in Pulmonary Arterial Hypertension

NCT05493371 | Completed Phase 2 DMC

• 3 other identifiers: 818662022-002400-202022-501512-33-00
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Idiopathic Pulmonary Arterial Hypertension

Keywords

Empagliflozin

Outcome Measures

Primary Outcomes (3)

• Tolerability: the number of patients who have to prematurely discontinue treatment due to intolerability or adverse events.

  12 weeks

• Feasibility: time needed to include all patients and number of patients needed to screen.

  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).

  12 weeks

Secondary Outcomes (14)

• Right ventricle ejection fraction (RVEF) measured using MRI

  12 weeks

• Right ventricle mass measured using MRI

  12 weeks

• Left ventricle ejection fraction (LVEF) measured using MRI

  12 weeks

• Stroke volume (SV) measured using MRI

  12 weeks

• Tricuspid annular plane systolic excursion (TAPSE) measured using transthoracic ultrasound

  12 weeks

Study Arms (1)

Empagliflozin

EXPERIMENTAL

Drug: Empagliflozin 10 MG

Interventions

Empagliflozin 10 MG DRUG

10 mg once daily empagliflozin oral tablets for 12 weeks

Empagliflozin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

Amsterdam UMC, location Vumc

Amsterdam, North Holland, 1081 HV, Netherlands

Location

MeSH Terms

Conditions

Familial Primary Pulmonary Hypertension

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Harm Jan Bogaard, Prof. dr.

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Model Details: prospective single-center, phase IIa, single arm, open label, interventional proof-of-concept study

Study Record Dates

• First Submitted: July 28, 2022
• First Posted: August 9, 2022
• Study Start: March 1, 2023
• Primary Completion: November 1, 2024
• Study Completion: November 1, 2024
• Last Updated: November 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Six months after study completion
• Access Criteria: data can be obtained on request by email

Locations

NL (1)