Inorganic Nitrates in Pulmonary Embolism With Hemodynamic Instability
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Mean pulmonary artery pressure (mPAP)
研究概览
简要总结
Pulmonary embolism (PE) is a serious condition caused by blood clots blocking the blood vessels in the lungs. In some patients, PE leads to increased pressure in the lung circulation and strain on the right side of the heart. Patients with intermediate high-risk PE have signs of right heart stress and heart muscle injury and are at risk of clinical deterioration despite standard treatment with anticoagulation.
In addition to the mechanical obstruction caused by blood clots, pulmonary embolism also causes narrowing of the lung blood vessels due to vasoconstriction. This increases pulmonary vascular resistance and contributes to elevated pressure in the pulmonary arteries, which can worsen right heart function. Treatments that reduce pulmonary artery pressure and vascular resistance could therefore potentially improve heart function and stabilize patients in the acute phase of PE. However, there is limited clinical evidence regarding the safety and effectiveness of pulmonary vasodilator therapy in this patient group.
Inorganic nitrates, found naturally in foods such as beetroot, are converted in the body to nitric oxide, a substance that relaxes blood vessels. Inorganic nitrates have been shown to lower blood pressure and improve pulmonary hemodynamics in other cardiovascular conditions, and are generally considered safe. Their effects in patients with intermediate high-risk pulmonary embolism have not previously been studied in a randomized controlled trial.
The aim of this study is twofold: first, to describe invasive hemodynamic measurements in patients with intermediate high-risk pulmonary embolism using right heart catheterization; and second, to investigate the safety, feasibility, and physiological effects of treatment with oral inorganic nitrate compared with placebo.
This is a multicenter, double-blind, randomized controlled trial conducted at two hospitals in Sweden. Adult patients with confirmed acute pulmonary embolism, right ventricular dilation, and elevated cardiac troponin levels will be included after providing informed consent. All patients will receive standard care, including anticoagulation therapy. In addition, all participants will undergo right heart catheterization to measure pressures and blood flow in the heart and lungs.
Participants will be randomly assigned to receive either nitrate-rich beetroot juice or a placebo beetroot juice for five days. Neither the patients nor the treating clinicians or investigators will know which treatment is given. The primary outcome is mean pulmonary artery pressure measured three hours after administration of the study treatment. Secondary outcomes include additional hemodynamic measurements, blood biomarkers, and safety outcomes such as low blood pressure or need for vasopressor treatment.
The results of this study will improve understanding of pulmonary hemodynamics in intermediate high-risk pulmonary embolism and help determine whether inorganic nitrate therapy is safe and has beneficial physiological effects in this patient population.
详细描述
Pulmonary embolism (PE) is a common and potentially life-threatening cardiovascular condition caused by obstruction of the pulmonary arteries by thromboembolic material. Acute PE may result in a sudden increase in pulmonary vascular resistance, leading to elevated pulmonary artery pressure, right ventricular (RV) dilatation, impaired RV function, and reduced cardiac output. Right ventricular failure is a major cause of morbidity and mortality in patients with acute PE.
Patients with intermediate high-risk pulmonary embolism are characterized by hemodynamic stability combined with evidence of RV dysfunction and myocardial injury, typically demonstrated by right ventricular dilatation on imaging and elevated cardiac biomarkers such as troponin. Although these patients are initially hemodynamically stable, they are at risk of clinical deterioration despite standard anticoagulation therapy.
The pathophysiology of hemodynamic compromise in acute PE is multifactorial and involves both mechanical obstruction of pulmonary blood flow and pulmonary vasoconstriction mediated by hypoxia, endothelial dysfunction, and release of vasoactive substances. This leads to increased pulmonary vascular resistance and elevated pulmonary artery pressures, resulting in increased RV afterload and impaired RV performance.
The present study aims to provide a detailed invasive hemodynamic characterization of patients with intermediate high-risk PE. Through right heart catheterization, the study will describe invasive hemodynamics and enable assessment of right ventricular afterload and right ventricular contractile performance using invasive pressure and flow-derived parameters. These measurements will improve understanding of the interaction between pulmonary vascular resistance, RV afterload, and RV function in the acute phase of PE.
Inorganic nitrates are dietary compounds that are converted in vivo to nitrite and nitric oxide, leading to nitric oxide-mediated vasodilation. Inorganic nitrate supplementation has been shown to lower systemic blood pressure and improve pulmonary hemodynamics in other cardiovascular conditions, and is generally considered safe. However, the physiological effects and safety of inorganic nitrate treatment in patients with intermediate high-risk pulmonary embolism have not previously been evaluated in a randomized controlled trial.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Acute PE with symptoms < 14 days confirmed by computer tomography (CT) AND RV dilatation on CT or ECHO AND Troponin T > 45 pg/ml
排除标准
- •Cardiac arrest with cardiopulmonary resuscitation, Thrombolysis or endovascular thrombectomy, < 18 years of age, Pregnancy, INR > 2,5 or platelet count < 100, DAPT or OAK, Inability to give informed consent to the study, Contraindications for right heart catheterization: mechanical devices, endocarditis, GUCH-patients, Short expected lifespan < 120 days / withdrawal of care, Imdur or other medications with nitrates, Daily usage of mouth wash prescribed by dentist or doctor
研究组 & 干预措施
Inorganic nitrate
14 cl of nitrate-rich beetroot juice
干预措施: nitrate-rich beetroot juice/placebo beetroot juice (Dietary Supplement)
Placebo
14 cl of visually and taste-matched placebo beetroot juice
干预措施: nitrate-rich beetroot juice/placebo beetroot juice (Dietary Supplement)
结局指标
主要结局
Mean pulmonary artery pressure (mPAP)
时间窗: 3 hours from administration of beetroot juice or placebo-juice.
Mean pulmonary artery pressure measured with right heart catheterization three hours after administration of beetroot juice or placebo-juice.
次要结局
未报告次要终点
研究者
Jacob Hollenberg
Profesor
Karolinska Institutet