Oxygen Therapy for Pulmonary Embolism

(SO-PE Trial)

Overseen By Blair Alden Parry, CCRC, BA

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Massachusetts General Hospital

Must not be taking: Vasodilators

Disqualifiers: Hemodynamic instability, COPD, CHF, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 180 minutes

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how supplemental oxygen (also known as oxygen therapy) can assist individuals with a sudden blood clot in the lungs, known as acute pulmonary embolism (PE). Researchers aim to determine if oxygen can improve heart function by reducing lung pressure. Participants will alternate between breathing oxygen and normal air to compare effects. The trial seeks individuals recently diagnosed with PE, experiencing new or worsening symptoms, and able to comfortably breathe room air. As an Early Phase 1 trial, this research focuses on understanding how oxygen therapy works in people, offering participants a chance to contribute to groundbreaking medical insights.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you've used vasodilator medication in the past 24 hours.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that most people tolerate extra oxygen therapy well. Some studies suggest it can help with severe lung blockages, known as pulmonary embolism, by reducing the blockage and lowering lung pressure.

The effects on individuals with normal oxygen levels remain unclear, but past studies have not identified any major safety concerns. Oxygen therapy is a common treatment for many conditions and is usually safe for most people. However, like any treatment, it may cause minor side effects, which are generally not serious. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pulmonary embolism?

Researchers are excited about this trial because it explores the potential benefits of oxygen therapy for treating pulmonary embolism (PE), a condition typically managed with anticoagulants like heparin or warfarin. Unlike traditional treatments that focus on blood thinning, this approach uses supplemental oxygen delivered by a non-rebreather face mask. The study aims to assess whether alternating between supplemental oxygen and room air can improve patient outcomes by optimizing oxygen levels in the blood. This trial could uncover new insights into non-pharmacological strategies for managing acute PE, potentially offering a complementary or alternative option to current medications.

What evidence suggests that oxygen therapy might be an effective treatment for pulmonary embolism?

Research has shown that extra oxygen can assist people with acute pulmonary embolism (PE) by easing breathing and reducing heart strain. In this trial, participants will receive either supplemental oxygen or room air via facemask. Studies have found that oxygen therapy can alleviate blood vessel constriction caused by low oxygen levels, reducing lung pressure and aiding the heart in pumping blood. Some early studies also suggest that oxygen might help clear lung blockages. Overall, these findings indicate that oxygen therapy could effectively manage PE symptoms. ^{1 2 4 6 7}

Who Is on the Research Team?

Christopher Kabrhel, MD, MPH

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

Adults over 18 with a recent pulmonary embolism confirmed by imaging, who can breathe on their own with oxygen saturation above 90%. Not for those unstable after the event, with new heart rhythm issues, pregnant, or on certain medications. Must be able to wear an oxygen mask.

Inclusion Criteria

Your oxygen level is at least 90% when you breathe normally without any extra oxygen.

I was diagnosed with a lung clot by a CT scan less than 24 hours ago.

My symptoms started less than 3 days ago.

Exclusion Criteria

My symptoms started more than 72 hours ago.

I am scheduled for a clot-dissolving treatment or clot removal surgery.

I have taken medication to widen my blood vessels in the last 24 hours.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive alternating treatments of supplemental oxygen or room air every 30 minutes for 90 minutes, followed by maintenance of the treatment for a total of 180 minutes

180 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Non-rebreather mask
• Oxygen Therapy

Trial Overview

The trial is testing if supplemental oxygen given through a non-rebreather mask can help manage acute pulmonary embolism by reducing stress on the right side of the heart and lowering blood pressure in lung arteries due to low oxygen levels.

How Is the Trial Designed?

Group I: Supplemental oxygen delivered by facemask Experimental Treatment 2 Interventions

Patients with acute PE will be randomized to breathing supplemental oxygen by non-rebreather face mask first. Subjects will alternate treatments (supplemental oxygen or room air) every 30 minutes for 90 minutes (e.g. T=30, T=60, T=90) and then will maintain their treatment (oxygen or room air) for a total of 180 minutes.

Group II: Room air delivered by facemask Active Control 1 Intervention

Patients with acute PE will be randomized to breathing room air by non-rebreather face mask first. Subjects will alternate treatments (supplemental oxygen or room air) every 30 minutes for 90 minutes (e.g. T=30, T=60, T=90) and then will maintain their treatment (oxygen or room air) for a total of 180 minutes.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

University of Aarhus

Collaborator

Trials

1,441

Recruited

14,600,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Aarhus University Hospital

Collaborator

Trials

847

Recruited

6,900,000+

Published Research Related to This Trial

Catheter-directed therapy (CDT) significantly reduced in-hospital mortality compared to systemic thrombolysis (ST), anticoagulation (AC), and surgical embolectomy (SE) in patients with intermediate to high-risk pulmonary embolism, based on a network meta-analysis of 11 RCTs and 42 observational studies involving 157,454 patients.

CDT also showed a lower rate of recurrent pulmonary embolism compared to ST and AC, while presenting a lower risk of major bleeding compared to ST and AC, indicating it may be a safer and more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of interventions for intermediate to high-risk pulmonary embolism: A network meta-analysis. Ishisaka, Y., Watanabe, A., Fujisaki, T., et al.[2023]

Thrombolytic therapy significantly reduces all-cause mortality in patients with pulmonary embolism compared to conventional anticoagulation, with a number needed to treat (NNT) of 59 based on a review of 16 trials involving 2115 patients.

However, this therapy also increases the risk of major bleeding and intracranial hemorrhage, with a number needed to harm (NNH) of 18 for major bleeding, indicating a need for careful consideration of risks versus benefits, especially in hemodynamically stable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. Chatterjee, S., Chakraborty, A., Weinberg, I., et al.[2022]

In a retrospective review of 7 patients who underwent pulmonary thromboembolectomy, surgery was performed successfully under cardiopulmonary bypass for cases of acute pulmonary thromboembolism when medical treatments failed, highlighting its role as a critical intervention.

Despite the surgery, there were significant post-operative complications, including hemothorax and effusions, and two patients died, indicating that while surgery can be lifesaving, it carries risks and should be considered when other treatments are ineffective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary thromboembolectomy for acute pulmonary thromboembolism. Yi, I., Park, JC., Cho, KS., et al.[2022]

Systemic fibrinolysis is the primary treatment for high-risk acute pulmonary embolism, effectively reversing right ventricular overload and improving hemodynamic stability, but it carries a significant risk of bleeding.

Catheter-directed therapies, both pharmacological and mechanical, may offer a safer alternative with quicker recovery of heart function, highlighting the need for further studies to determine the best approach for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Update on the Management of Acute High-Risk Pulmonary Embolism. Chopard, R., Behr, J., Vidoni, C., et al.[2022]

A patient with massive pulmonary embolism was successfully treated using catheter-directed therapy combined with extracorporeal membrane oxygenation (ECMO) for hemodynamic support, highlighting an effective intervention for this serious condition.

The case underscores the potential complications associated with catheter-directed therapy, emphasizing the need for careful consideration in treatment planning for massive PE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Massive Pulmonary Embolism Treated with Catheter Therapy and Extracorporeal Membrane Oxygenation. Teman, NR., Xiao, JT., Tribble, CG.[2018]

The study is investigating the effects of inhaled nitric oxide (NO) combined with oxygen on patients with submassive pulmonary embolism (PE), aiming to improve right ventricular function and reduce strain, with a sample size of 78 patients.

So far, the trial has shown no safety concerns, as no serious adverse events related to NO have occurred, indicating that inhaled NO may be a safe treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of inhaled nitric oxide to treat acute pulmonary embolism: The iNOPE trial. Kline, JA., Hall, CL., Jones, AE., et al.[2023]

In a study of 81 patients with intermediate-high-risk pulmonary embolism, low-dose urokinase (UK) therapy showed a higher rate of CTPA-confirmed absorption compared to standard anticoagulant therapy, indicating better efficacy in resolving the embolism.

The use of low-dose UK also resulted in lower incidences of dyspnea at both discharge and long-term follow-up, while not increasing the risk of major bleeding or affecting mortality rates, suggesting it is a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose urokinase thrombolytic therapy for patients with acute intermediate-high-risk pulmonary embolism: A retrospective cohort study. Weng, C., Wang, X., Huang, L., et al.[2021]

An adolescent boy with a massive pulmonary embolism was successfully treated with intravenous thrombolytic therapy, receiving 1.3 mg/kg of rt-PA over 2 hours, highlighting the potential efficacy of this treatment in children despite the low incidence of pulmonary embolism in this age group.

Thrombolytic therapy is generally considered for hemodynamically unstable patients with pulmonary embolism, and recent studies suggest that even hemodynamically stable patients with right-ventricular dysfunction may also benefit from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thrombolysis in pulmonary embolism: an adolescent with protein S deficiency. Degan, TA.[2016]

Venous thromboembolic disease, particularly acute pulmonary embolus (PE), has a high mortality rate of up to 50%, highlighting the need for effective treatment strategies.

New interventional therapies, such as catheter-directed thrombolysis and extracorporeal membrane oxygenation, are being developed to improve outcomes for high and intermediate-high risk PE patients, emphasizing the importance of a multidisciplinary approach and patient risk stratification in management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interventional therapies in acute pulmonary embolus-current trends and future directions. Patel, S., Thulasidasan, N., Thomson, B., et al.[2023]

In a study of 16 patients with acute high-risk pulmonary embolism (PE) treated with extracorporeal membrane oxygenation (ECMO), the overall 30-day mortality rate was 43.8%, indicating significant risks associated with this severe condition despite aggressive treatment.

ECMO was used as a rescue therapy for patients experiencing refractory shock or cardiac arrest, with varying outcomes based on additional treatments like thrombolysis and embolectomy, highlighting the complexity of managing acute high-risk PE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of extracorporeal membrane oxygenation in patients with acute high-risk pulmonary embolism: a case series with literature review. Oh, YN., Oh, DK., Koh, Y., et al.[2022]

In a pilot trial involving 70 nonhypoxemic patients with intermediate-risk pulmonary embolism, supplemental oxygen therapy did not significantly improve the normalization of right ventricle size compared to ambient air after 48 hours, with 42.4% of the oxygen group achieving normalization versus 21.6% in the control group (P = 0.08).

However, the oxygen group showed a significant reduction in the right ventricle to left ventricle diameter ratio from baseline to 48 hours, indicating some potential benefits in cardiac function, which warrants further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen Therapy in Patients With Intermediate-Risk Acute Pulmonary Embolism: A Randomized Trial. Barrios, D., Durán, D., Rodríguez, C., et al.[2023]

Anticoagulant therapy, using either unfractionated or low-molecular-weight heparins along with a vitamin K antagonist, is effective for the majority of clinically stable pulmonary embolism (PE) patients, helping to prevent thrombus extension and reduce mortality.

For about 15-20% of patients with severe clinical instability, prompt intravenous thrombolysis is a life-saving treatment, while the optimal therapy for normotensive patients with right ventricular dysfunction remains uncertain and requires further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary embolism: treatment of the acute episode. Casazza, F., Roncon, L., Greco, F.[2005]

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