Oxygen Therapy for Pulmonary Embolism

(SO-PE Trial)

Overseen By Blair A 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

Trial Summary

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.

What data supports the effectiveness of oxygen therapy for pulmonary embolism?

The research suggests that while oxygen therapy is commonly used, its specific effectiveness for pulmonary embolism, especially in patients without low oxygen levels, is uncertain. However, combining oxygen with other treatments like inhaled nitric oxide may improve heart function and breathing in some patients with pulmonary embolism. ^{1 2 3 4 5}

Is oxygen therapy safe for humans?

The research does not provide specific safety data on oxygen therapy for pulmonary embolism, but oxygen therapy is generally considered safe for humans when used appropriately. ^{2 3 6 7 8}

How is oxygen therapy different from other treatments for pulmonary embolism?

Oxygen therapy for pulmonary embolism is unique because it focuses on providing supplemental oxygen to improve oxygen levels in the blood, unlike other treatments that primarily aim to dissolve or remove the blood clot, such as thrombolysis or surgical procedures. This approach can be particularly beneficial for patients experiencing severe breathing difficulties due to the embolism. ^{2 9 10 11 12}

What is the purpose of this trial?

A study of how supplemental oxygen helps patients with acute pulmonary embolism (PE). Hypothesis: Oxygen affects right ventricular dysfunction (RVD) in patients with acute pulmonary embolism (PE) primarily by relieving hypoxic pulmonary vasoconstriction and reducing pulmonary pressure (PA) pressure, and that this process is metabolically driven.

Research Team

Christopher Kabrhel, MD, MPH

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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 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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Randomized trial of inhaled nitric oxide to treat acute pulmonary embolism: The iNOPE trial. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Interventional therapies in acute pulmonary embolus-current trends and future directions. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Oxygen Therapy in Patients With Intermediate-Risk Acute Pulmonary Embolism: A Randomized Trial. [2023]

4. Italy pubmed.ncbi.nlm.nih.gov

Pulmonary embolism: treatment of the acute episode. [2005]

5. Switzerland pubmed.ncbi.nlm.nih.gov

An Update on the Management of Acute High-Risk Pulmonary Embolism. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Comparison of interventions for intermediate to high-risk pulmonary embolism: A network meta-analysis. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Low-dose urokinase thrombolytic therapy for patients with acute intermediate-high-risk pulmonary embolism: A retrospective cohort study. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

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

9. United States pubmed.ncbi.nlm.nih.gov

Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. [2022]

10. Korea (South) pubmed.ncbi.nlm.nih.gov

Use of extracorporeal membrane oxygenation in patients with acute high-risk pulmonary embolism: a case series with literature review. [2022]

11. Korea (South) pubmed.ncbi.nlm.nih.gov

Pulmonary thromboembolectomy for acute pulmonary thromboembolism. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Massive Pulmonary Embolism Treated with Catheter Therapy and Extracorporeal Membrane Oxygenation. [2018]