Glycocalyx Restoration in Chronic Heart Failure: a Proof of Concept, Randomized, Double-blind, Placebo-controlled Study
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 64
- 试验地点
- 3
- 主要终点
- Percent change of NT-proBNP from baseline to week 8 in Endocalyx treated patients when compared with subject receiving Placebo
研究概览
简要总结
The goal of this randomized, double-blind, placebo-controlled study is to assess whether the food supplement Endocalyx Pro reduces sodium and water excess in patients with chronic heart failure.
The main questions it aims to answer are:
- To assess whether the food supplement Endocalyx reduces sodium and water excess in patients with chronic heart failure.
- To determine the contribution of different potential working mechanisms of Endocalyx in heart failure patients.
- To evaluate whether the food supplement Endocalyx will improve patient-reported outcomes such as fluid overload symptoms and quality of life.
- To confirm the previously demonstrated safety of Endocalyx in subjects with chronic heart failure.
Participants will be randomized to Endocalyx Pro or Placebo daily for 8 weeks, and will be followed 12 weeks.
详细描述
Primary Objective:
1. To assess whether the food supplement Endocalyx Pro™ (further termed Endocalyx) reduces sodium and water excess in patients with chronic heart failure.
Secondary Objectives:
-
To evaluate whether Endocalyx will improve physical limitations and patient-reported outcomes such as fluid overload symptoms and quality of life.
-
To determine the working mechanisms of Endocalyx in heart failure patients.
-
To determine whether Endocalyx will alter tissue sodium content.
-
To analyze whether Endocalyx reduces total body water and body weight.
-
To assess whether Endocalyx affects office blood pressure, 24-hour blood pressure, peripheral resistance and cardiac output.
-
To assess whether Endocalyx improves microcirculation characteristics.
-
To evaluate whether Endocalyx reduces systemic inflammation and monocyte activation.
-
To confirm safety of Endocalyx in the heart failure population a. To compare the incidence of (serious) adverse events between Endocalyx and placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double blind
入排标准
- 年龄范围
- 18 Years 至 110 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented or suspected heart failure with reduced ejection fraction (HFrEF and HFmrEF according to ESC guidelines).
- •Signs of congestion, defined as:
- •a. Elevated NT-proBNP levels: i. >450 pg/ml in subjects aged <55 years. ii. >900 pg/ml in subjects aged 55-75 years. iii. >1800 pg/ml in subjects aged >75 years. AND b. Use of diuretics, OR c. Presence of peripheral edema, OR d. Complaints of orthopnea or paroxysmal nocturnal dyspnea, OR e. A chest X-rays with sings of volume overload, OR f. Hypertension, as defined by an office blood pressure >140/90 mmHg.
- •Stable diuretic and antihypertensive treatment for the previous 3 weeks.
- •Subject, or legal representative, has voluntarily signed and dated an Informed Consent Form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study has been explained and the subject has had the opportunity to ask questions. The informed consent must be signed before any study-specific procedures are performed.
- •Rationale for the inclusion criteria:
- •(1-3) To select the adequate subject population with appropriate disease severity for the evaluation. NT-proBNP levels are known to increase with age.(21, 22) The cutoffs of NT-proBNP levels were selected according the 2021 European Society of Cardiology Guidelines for the diagnosis and treatment of acute and chronic heart failure. (23) (4) In accordance with GCP.
- •Should inclusion prove difficult, we will lower required NT-proBNP levels by 25% to respectively 338, 675 and 1350 pg/ml. We will notify the METC of this decision.
排除标准
- •Age <18 years.
- •Estimated glomerular filtration rate (eGFR) <15 ml/min/1.73m2 measured by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
- •Severe symptoms of (orthostatic) hypotension.
- •An acute coronary syndrome, stroke, transient ischemic attack or cardiovascular surgery in the last 3 months.
- •Hospitalization for heart failure in the past 3 weeks.
- •Dialysis treatment or expected initiation of dialysis within 3 months of screening.
- •Women of child bearing potential.
- •Planned surgery in the next 8 weeks.
- •Major surgery in the previous 4 weeks.
- •Use of any other investigational drug.
- •Presence of significant comorbidities (e.g., advanced malignancy, advanced liver disease) with a life expectancy of less than 1 year.
- •A psychiatric, addictive or any disorder that compromises ability to give truly informed consent for participation in this study.
- •Known hypersensitivity to seaweed, corn, artichoke, grape, melon or to any of the excipients of Endocalyx.
- •Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption.
结局指标
主要结局
Percent change of NT-proBNP from baseline to week 8 in Endocalyx treated patients when compared with subject receiving Placebo
时间窗: 8 weeks
Our primary outcome will be the degree of volume overload as measured by the change in NT-proBNP from baseline to the study end at 8 weeks. We will compare the proportional change in NT-proBNP from baseline (as defined by the geometric mean of the screening and week 0 visit) to week 8 in a logarithmic scale using an analysis of covariance (ANCOVA). Treatment will be included in the model as fixed factor, and gender (male versus female) and baseline NT-proBNP as covariates. Our primary analysis will be an intention-to-treat analysis. To check the robustness of our results, we will perform a per protocol analysis. Subjects that withdraw their consent and stop the study medication will be asked to consent for a NT-proBNP measurement at the scheduled end of the study. NT-proBNP will be measured at screening visit, week 0 (randomization), week 4 and 8
Change in NT-proBNP in patients with chronic heart failure with (mildly) reduced ejection fraction.
时间窗: 8 weeks
Our primary outcome will be the degree of volume overload as measured by the change in NT-proBNP from baseline to the study end at 8 weeks. The primary analysis will be performed using a mixed model for repeated measures (MMRM) on log-transformed NT-proBNP values. We will first fit models to analyze the overall treatment effect, and thereafter fit different models to assess the treatment effect over time (visit-specific). Our primary analysis will be an intention-to-treat analysis. To check the robustness of our results, we will perform a per protocol analysis. Subjects that withdraw their consent and stop the study medication will be asked to consent for a NT-proBNP measurement at the scheduled end of the study. NT-proBNP will be measured at screening visit, week 0 (randomization), week 4 and 8
次要结局
- Lipopolysaccharide-mediated cytokine secretion of monocytes in vitro in Endocalyx treated patients when compared with subjects receiving Placebo(8 weeks)
- Change/difference in blood pressure in Endocalyx treated patients when compared with subjects receiving Placebo(12 weeks)
- Plasma aldosterone and renin change/difference in Endocalyx treated patients when compared with subjects receiving Placebo(8 weeks)
- Change in 24 hour blood pressure, daytime blood pressure, nighttime blood pressure in Endocalyx treated patients when compared with subject receiving Placebo(8 weeks)
- Change in body weight (in kilograms) in Endocalyx treated patients when compared with subject receiving Placebo(8 weeks)
- Difference in chemokine. scavenger receptors, and surface proteins associated with monocyte adhesion, migration and activation concentrations, in Endocalyx treated patients when compared with subject receiving Placebo(8 weeks)
- Distance covered during the 6 minute walking tests in Endocalyx treated patients when compared with subjects receiving Placebo(8 weeks)
- Pharmacokinetics of Endocalyx(0-8 weeks)
- monocyte and macrophage expression and density in skin biopsies(0-8 weeks)
- Difference/Change in 24-hour urine sodium and potassium excretion in Endocalyx treated patients when compared with subjects receiving Placebo(8 weeks)
- Percent change in antihypertensive drug dosage or number prescribed(8 weeks)
- Concentration change of Adrenomedullin in Endocalyx treated patients when compared with subject receiving Placebo(0-8 weeks)
- Change/difference in ratio of classical (CD14++/CD16-), non-classical (CD14+/CD16++) and intermediate (CD14++/CD16+) monocyte subsets in Endocalyx treated patients when compared with subject receiving Placebo(0-8 weeks)
- Difference in hospitalization rates due to heart failure in Endocalyx treated patients when compared with subjects receiving Placebo(12 weeks)
- Differential treatment effects of Endocalyx in male and female patients(12 weeks)
- Change in total body water in Endocalyx treated patients when compared with subject receiving Placebo(8 weeks)
- Change in hemodynamic parameters in Endocalyx treated patients when compared with subject receiving Placebo(8 weeks)
- Change in self-reported Quality of life in Endocalyx treated patients when compared with subjects receiving Placebo(8 weeks)
- Percent change in diuretics (dosage or number prescribed)(8 weeks)
- Difference in incidence of (serious) adverse events in Endocalyx treated patients when compared with subjects receiving Placebo(12 weeks)
- Skin sodium content in skin biopsies(0-8 weeks)
- Change/difference in ratio of classical, non-classical and intermediate monocyte subsets.(0-8 weeks)
- Change from baseline in total vessel density and perfused vessel density(8 weeks)
- Change from baseline in VEGF-C(8 weeks)
- Change from baseline in proportion of perfused vessels(8 weeks)
- Change from baseline in microvascular flow index(8 weeks)
- Change from baseline in microvascular health score(8 weeks)
- Change from baseline in transepidermal water loss(8 weeks)
- Change from baseline in skin hydration(8 weeks)
- Change from baseline in VEGF-A(8 weeks)
- Change from baseline in Angiopoietin 1(8 weeks)
- Change from baseline in Angiopoietin 2(8 weeks)
- Change from baseline in TIE2(8 weeks)
研究者
Rik Olde Engberink
MD PhD
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)