NCT05493371已完成2 期
Feasibility Study of Empagliflozin As Treatment for Idiopathic Pulmonary Arterial Hypertension
Amsterdam UMC, location VUmc1 个研究点 分布在 1 个国家目标入组 8 人开始时间: 2023年3月1日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Tolerability: the number of patients who have to prematurely discontinue treatment due to intolerability or adverse events.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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
- •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
研究组 & 干预措施
Empagliflozin
Experimental
干预措施: Empagliflozin 10 MG (Drug)
结局指标
主要结局
Tolerability: the number of patients who have to prematurely discontinue treatment due to intolerability or adverse events.
时间窗: 12 weeks
Feasibility: time needed to include all patients and number of patients needed to screen.
时间窗: 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).
时间窗: 12 weeks
次要结局
- 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)
研究者
Harm Jan Bogaard
Prof. Dr.
VU University of Amsterdam
研究点 (1)
Loading locations...
相似试验
进行中（未招募）
2 期
Feasibility of Study of Empagliflozin in Patients With Autosomal Dominant Polycystic Kidney DiseasePolycystic Kidney, Autosomal DominantNCT05510115University of Colorado, Denver50
已完成
3 期
EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced)Heart FailureNCT03057977Boehringer Ingelheim3,730
已完成
3 期
This Study Tests Empagliflozin in Patients With Chronic Heart Failure With Reduced Ejection Fraction (HFrEF). The Study Looks at How Far Patients Can Walk in 6 Minutes and at Their Heart Failure SymptomsHeart FailureNCT03448419Boehringer Ingelheim312
已完成
3 期
This Study Tests Empagliflozin in Patients With Chronic Heart Failure With Preserved Ejection Fraction (HFpEF). The Study Looks at How Far Patients Can Walk in 6 Minutes and at Their Heart Failure Symptoms.Heart FailureNCT03448406Boehringer Ingelheim315
已完成
3 期
Diabetes Study of Linagliptin and Empagliflozin in Children and Adolescents (DINAMO)TMDiabetes Mellitus, Type 2NCT03429543Boehringer Ingelheim175