Inorganic Nitrates in Intermediate High-risk Pulmonary Embolism

NCT07431229 | Recruiting

• 1 other identifier: NITRATE-PE
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief 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)

Keywords

Pulmonary embolism; Pulmonary vasodilation; Invasive hemodynamics; right heart catheterization

Outcome Measures

Primary Outcomes (1)

• Mean pulmonary artery pressure (mPAP)

  Mean pulmonary artery pressure measured with right heart catheterization three hours after administration of beetroot juice or placebo-juice.

  3 hours from administration of beetroot juice or placebo-juice.

Study Arms (2)

Inorganic nitrate

EXPERIMENTAL

14 cl of nitrate-rich beetroot juice

Dietary Supplement: nitrate-rich beetroot juice/placebo beetroot juice

Placebo

PLACEBO COMPARATOR

14 cl of visually and taste-matched placebo beetroot juice

Dietary Supplement: nitrate-rich beetroot juice/placebo beetroot juice

Interventions

nitrate-rich beetroot juice/placebo beetroot juice DIETARY_SUPPLEMENT

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.

Also known as: right heart catheterization

Inorganic nitrate; Placebo

Eligibility Criteria

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

You may qualify if:

• Acute PE with symptoms \< 14 days confirmed by computer tomography (CT) AND RV dilatation on CT or ECHO AND Troponin T \> 45 pg/ml

You may not qualify if:

• 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

Sponsors & Collaborators

• Karolinska Institutet: lead
• South Hospital Stockholm: collaborator

Study Sites (2)

South hospital Stockholm

Stockholm, Sweden

RECRUITING

Stockholm, Sweden

Stockholm, Sweden

NOT YET RECRUITING

Related Publications (1)

• Helms J, Carrier M, Klok FA. High-risk pulmonary embolism in the intensive care unit. Intensive Care Med. 2023;49(5):579-582. Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing G-J, Harjola V-P, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2019;41(4):543-603. Andersen A, Waziri F, Schultz JG, Holmboe S, Becker SW, Jensen T, et al. Pulmonary vasodilation by sildenafil in acute intermediate-high risk pulmonary embolism: a randomized explorative trial. BMC Pulm Med. 2021;21(1):72. Jones DA, Beirne AM, Kelham M, Wynne L, Andiapen M, Rathod KS, et al. Inorganic nitrate benefits contrast-induced nephropathy after coronary angiography for acute coronary syndromes: the NITRATE-CIN trial. Eur Heart J. 2024;45(18):1647-1658. Henrohn D, Björkstrand K, Lundberg JO, Granstam SO, Baron T, Ingimarsdóttir IJ, et al. Effects of oral supplementation with nitrate-rich beetroot juice in patients with pulmonary arterial hypertension: results from BEET-PAH, an exploratory randomized, double-blind, placebo-controlled, crossover study. J Card Fail. 2018;24(10):640-653. Kapil V, Milsom AB, Okorie M, Maleki-Toyserkani S, Akram F, Rehman F, et al. Inorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived nitric oxide. Hypertension. 2010;56(2):274-281. Hoeper MM, Lee SH, Voswinckel R, Palazzini M, Jais X, Marinelli A, et al. Complications of right heart catheterization procedures in patients with pulmonary hypertension in experienced centers. J Am Coll Cardiol. 2006;48(12):2546-2552.

  BACKGROUND

MeSH Terms

Conditions

Pulmonary Embolism; Disease

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jacob M Hollenberg, Professor

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jacob M Hollenberg, Professor

CONTACT

(+46) 070-4133442; jacob.hollenberg@ki.se

Olle M Andersson, PhD

CONTACT

(+46) 072-9174349; olle.andersson@ki.se

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Profesor

Study Record Dates

• First Submitted: February 18, 2026
• First Posted: February 24, 2026
• Study Start: February 17, 2026
• Primary Completion (Estimated): February 25, 2028
• Study Completion (Estimated): February 25, 2028
• Last Updated: February 24, 2026

Record last verified: 2026-02

Locations

SE (2)