Inorganic Nitrates in Intermediate High-risk Pulmonary Embolism

Summary

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.

Conditions

• Pulmonary Embolism (Diagnosis)

Interventions

DIETARY_SUPPLEMENT

nitrate-rich beetroot juice/placebo beetroot juice

After written informed consent is obtained, all patients will undergo right heart catheterization to obtain invasive hemodynamic measurements at baseline. The experimental arm will drink 14 cl of nitrate-rich beetroot juice. The placebo comparator arm will drink 14 cl of visually and taste-matched placebo beetroot juice.

Sponsors & Collaborators

• South Hospital Stockholm

  collaborator UNKNOWN

• Karolinska Institutet

  lead OTHER

Principal Investigators

• Jacob M Hollenberg, Professor · Karolinska Institutet

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-02-17

Primary Completion

2028-02-25

Completion

2028-02-25

Countries

• Sweden

Study Locations