Catheter-directed Thrombolysis for Pulmonary Embolism (HI-PEITHO Trial)
Recruiting in Palo Alto (17 mi)
+67 other locations
Overseen ByStavros Konstantinides, MD
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Boston Scientific Corporation
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial compares two treatments for blood clots in the lungs in patients at higher risk of complications. One treatment uses only blood thinners, while the other combines blood thinners with a device that uses sound waves to break up clots. The goal is to see which treatment is better at reducing serious problems and death.
Will I have to stop taking my current medications?
The trial requires that you stop taking certain blood thinners and antiplatelet medications before participating. If you are on medications like apixaban, rivaroxaban, dabigatran, edoxaban, or certain antiplatelet agents, you may need to stop them before joining the study.
What data supports the effectiveness of the treatment for pulmonary embolism?
Research shows that low molecular weight heparins (a type of blood thinner) are effective and safe for treating pulmonary embolism, with fewer bleeding complications compared to traditional unfractionated heparin. They are also easier to administer and do not require frequent dose adjustments, making them a promising option for treating this condition.
12345Is catheter-directed thrombolysis for pulmonary embolism generally safe in humans?
Low-molecular-weight heparins, which are used in treating conditions like pulmonary embolism, have been shown to be safe and effective in several studies. They are often preferred over unfractionated heparin due to fewer side effects, such as bleeding, and can be administered without the need for regular monitoring.
13678How is the treatment with the EkoSonic Endovascular System and heparin different from other treatments for pulmonary embolism?
The EkoSonic Endovascular System combined with heparin is unique because it uses a catheter-directed approach to deliver medication directly to the clot in the lungs, potentially enhancing the effectiveness of the treatment compared to standard anticoagulation therapies that are administered systemically.
29101112Eligibility Criteria
Adults aged 18-80 with a recent diagnosis of acute pulmonary embolism, at elevated risk of early death or hemodynamic collapse, but not in shock or needing intensive care for other reasons. They must have certain clinical signs like increased heart rate and specific blood test results. Excluded are those who've had major bleeding issues, strokes, certain surgeries recently, severe infections like COVID-19 if it's not the main issue, pregnant women, and people on some chronic medications.Inclusion Criteria
I am between 18 and 80 years old.
I have a confirmed pulmonary embolism shown by a CT scan.
Exclusion Criteria
I have had bleeding in my brain or eyes at some point.
I only take low-dose aspirin or clopidogrel for my chronic condition, not both.
I am currently experiencing active bleeding.
I have not had a cardiac arrest or needed CPR recently.
I have had a stroke or mini-stroke in the last 6 months, or any time before that which left me permanently disabled.
I have a brain tumor or cancer that has spread to my brain.
I am on a long-term blood thinner like apixaban or rivaroxaban.
I have taken apixaban or rivaroxaban within the last 12 hours.
I am on chronic vitamin K treatment or have a blood clotting disorder with an INR > 1.5.
I have experienced shock due to a pulmonary embolism, with low blood pressure and signs of poor organ function.
Participant Groups
The HI-PEITHO study is testing two treatments for pulmonary embolism: standard anticoagulation therapy alone versus anticoagulation plus the EkoSonicTM Endovascular System to break up clots. Participants will be randomly assigned to one of these treatments and monitored over a year through several follow-ups to see which treatment reduces death and complications more effectively.
2Treatment groups
Active Control
Group I: Anticoagulation and EkoSonicTM Endovascular SystemActive Control2 Interventions
Low-molecular weight heparin (LMWH) or unfractionated heparin (UFH) and EkoSonicTM Endovascular System \[ultrasound-facilitated catheter-directed delivery of thrombolytic: 2 mg bolus/catheter + 1 mg/hour/catheter for 7 hours (total of 9 or 18 mg\]
Group II: AnticoagulationActive Control1 Intervention
Low-molecular weight heparin (LMWH) or unfractionated heparin (UFH)
Anticoagulation with heparin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:
🇪🇺 Approved in European Union as Heparin for:
- Venous thromboembolism
- Pulmonary embolism
- Deep vein thrombosis
- Acute coronary syndrome
🇺🇸 Approved in United States as Heparin for:
- Venous thromboembolism
- Pulmonary embolism
- Deep vein thrombosis
- Acute coronary syndrome
🇨🇦 Approved in Canada as Heparin for:
- Venous thromboembolism
- Pulmonary embolism
- Deep vein thrombosis
- Acute coronary syndrome
🇯🇵 Approved in Japan as Heparin for:
- Venous thromboembolism
- Pulmonary embolism
- Deep vein thrombosis
- Acute coronary syndrome
🇨🇳 Approved in China as Heparin for:
- Venous thromboembolism
- Pulmonary embolism
- Deep vein thrombosis
- Acute coronary syndrome
🇨🇭 Approved in Switzerland as Heparin for:
- Venous thromboembolism
- Pulmonary embolism
- Deep vein thrombosis
- Acute coronary syndrome
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Newark Beth Israel Medical CenterNewark, NJ
Augusta UniversityAugusta, GA
Baptist Health East LouisvilleLousville, KY
Kettering HealthKettering, OH
More Trial Locations
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Who is running the clinical trial?
Boston Scientific CorporationLead Sponsor
University Medical Center MainzCollaborator
National PERT Consortium, Inc.Collaborator
References
Low molecular weight heparin versus unfractionated heparin in the initial treatment of venous thromboembolism. [2019]In this review, we analyze data from randomized trials in which low molecular weight heparin was compared with unfractionated heparin, both to estimate the treatment effect of low molecular weight heparin in the initial treatment of venous thromboembolism and to evaluate the effect of the varied proportion of included cancer patients (6% to 22.7%) on the incidence of outcome events (recurrence of venous thromboembolism, bleeding, and mortality) and on the estimated treatment effect. Low molecular weight heparin has been extensively investigated in patients with deep vein thrombosis, but few trials have included patients with pulmonary embolism. The risk of recurrence of venous thromboembolism (odds ratio, 0.77; 95% CI, 0.56-1.04), major bleeding (odds ratio, 0.60; 95% CI, 0.38-0.95), and mortality (odds ratio, 0.72; 95% CI, 0.55-0.96) was less with low molecular weight heparins compared with unfractionated heparin. The proportion of cancer patients in these studies had a statistically significant effect on the incidence of recurrent venous thromboembolism (P = 0.03) and mortality (P = 0.002), but no influence on the estimated treatment effects of low molecular weight heparins. Low molecular weight heparin is effective and safe in the initial treatment of venous thromboembolism.
Anticoagulant agents in the management of pulmonary embolism. [2019]The anticoagulant agents most commonly used in the prevention and treatment of pulmonary embolism (PE) are unfractionated heparin, oral anticoagulants, and low molecular weight heparins (LMWHs). Unfractionated heparin at low fixed dose is the prophylactic regimen of choice for PE in patients undergoing general surgery or with serious medical diseases (low to moderate risk patients). In high risk patients perioperative prophylaxis with LMWHs or oral anticoagulants should be adopted. Therapy of pulmonary embolism should start with an intravenous bolus dose of 5000 U heparin followed by an infusion of 1250 U/h. Then the dose should be adjusted to maintain the aPTTX2-2.5 pre-treatment value. Heparin is continued for 7-10 days and is followed by oral anticoagulants for at least 3 months. Unfractionated heparin has some pharmacological limitations, mainly due to the aspecific binding to plasma proteins that limits its anticoagulant effect and causes the heparin resistance observed in some patients with PE and the inter-subject variability of the anticoagulant effect. Other antithrombotic agents such as LMWHs and selective thrombin inhibitors (hirudin and its analogues) do not aspecifically bind to plasma proteins. They have recently been used with promising results in the prevention and treatment of PE. Their definitive value in this clinical setting will be defined by the ongoing clinical trials.
Low-molecular-weight heparin in the treatment of pulmonary embolism. [2007]Unfractionated heparin is the traditional treatment of choice for patients presenting with submassive pulmonary embolism. However, newer low-molecular-weight heparins have been developed and tested in several clinical trials in the last 2 decades because of the many limitations of unfractionated heparin. The pharmacologic properties of the low-molecular-weight heparins allow them to be administered subcutaneously in fixed, weight-adjusted doses without need for laboratory monitoring. Different studies have recently proved their efficacy in the treatment of patients with deep vein thrombosis. Because there is good evidence that deep vein thrombosis and pulmonary embolism are 2 expressions of a single disease, the use of low-molecular-weight heparins has been extended to patients presenting with clinically stable pulmonary embolism. In particular, the results of 2 important clinical trials, the Columbus and the Thésée, have conclusively proved that the low-molecular-weight heparins are as safe and effective as unfractionated heparin. In some centers, approximately 80% of patients with deep vein thrombosis are treated at home. This suggests that carefully selected patients with clinically stable pulmonary embolism can receive home treatment with low-molecular-weight heparins.
[Role of low molecular weight heparins for treating non-massive pulmonary embolism]. [2016]Pulmonary revascularization after submassive pulmonary embolism can be achieved within 14 days in 50% of the patients treated with intravenous heparin then oral anticoagulants. Recurrence is estimated at 5% and risk of severe haemorrhage at 5 to 6%. For deep vein thrombosis, low-molecular weight heparins are at least as effective as unfractionated heparin and have a comparable or lower rate of complications. For submassive pulmonary embolism, two low-molecular weight heparins (calcium nadroparin and sodium dalteparin) have been compared with unfractionated heparin. Pulmonary revascularization on day 8 was about 68% for all treatment regimens. No cases of recurrent embolism were recorded and no severe haemorrhage occurred in patients given low-molecular weight heparin but did occur in 6% of those given unfractionated heparin. These early results, together with easy subcutaneous administration and the absence of daily dose adaptation requirement, suggest that low-molecular weight heparins could play a major role in treating submassive pulmonary embolism and thromboembolism in general.
Therapeutic application of subcutaneous low-molecular-weight heparin in acute venous thrombosis. [2018]Fifty patients presenting with acute deep-vein thrombosis were randomized in a prospective, controlled study to determine the safety and efficacy of a treatment with low-molecular-weight (LMW) heparin compared with unfractionated heparin. LMW heparin (n = 24) was administered twice daily subcutaneously at a dose of 2 X 150 anti-Xa units/kg body weight, and unfractionated heparin (n = 26) was given intravenously by continuous infusion at a dose of 450 anti-Xa units/kg body weight daily for 10 days. Doses were adjusted to maintain peak anti-Xa levels between 0.5 and 1.0 anti-Xa units per milliliter. One patient in the unfractionated heparin group and 2 patients in the LMW heparin group suffered from bleeding complications. Two patients on LMW heparin and on unfractionated heparin had high evidence of pulmonary embolism based on defects on ventilation-perfusion scintigraphy. Control phlebography and duplex sonography demonstrated a significant improvement during both treatment regimens. Reperfusion of the deep-vein system was 70% with LMW heparin and 75% with unfractionated heparin. The anti-Xa levels were significantly higher in the LMW heparin group, and activated partial thromboplastin and thrombin clotting times were significantly higher in the group receiving unfractionated heparin. Thrombin-antithrombin III complexes and D-dimer concentration decreased during the treatment, but did not differ between the two regimens. At the end of the treatment period with LMW heparin, protein C and antithrombin III were significantly higher.
The role of low-molecular-weight heparins in non-ST-segment elevation acute coronary syndromes. [2007]Acute coronary syndromes are believed to be mediated by plaque rupture, initiation of the coagulation cascade, and platelet activation and aggregation. Compared to unfractionated heparin, the low molecular weight heparins possess several important theoretical advantages for the treatment of patients with acute coronary syndromes, including less non-specific binding, resistance to inactivation by platelet factor-4, more reliable anticoagulation effects, and greater factor anti-Xa activity. Four large studies have compared low-molecular-weight heparin therapy with unfractionated heparin therapy in patients with acute coronary syndromes. Two studies involving enoxaparin (Lovenox) have demonstrated that this therapy results in a lower incidence of adverse events compared to treatment with unfractionated heparin. One study of dalteparin (Fragmin) and one of nadroparin (Fraxiparin) have demonstrated comparable results between these low-molecular-weight heparins and unfractionated heparin. Several studies of modest size have demonstrated that low-molecular-weight heparins can be safely combined with platelet glycoprotein IIb/IIIa inhibitors. Ongoing and upcoming studies should add to current knowledge of the utilization of low-molecular-weight heparins.
Low-molecular-weight heparins in the treatment of acute coronary syndromes. [2019]Platelet aggregation and activation of coagulation are key events in the development of acute coronary syndromes. Patients with an acute coronary syndrome are at high risk of death or myocardial infarction, and hence there is a strong rationale for the use of antithrombotic agents. Heparin has been shown to reduce the risk of death or myocardial infarction in aspirin-treated patients with acute coronary syndromes, but it has a number of limitations, including the need for regular monitoring and the risk of hemorrhage and thrombocytopenia. Low-molecular-weight heparins offer a number of practical and clinical advantages over unfractionated heparin, such as higher bioavailability and administration by subcutaneous injection. Several low-molecular-weight heparins are available that differ in their biochemical and pharmacologic properties, and it is not possible to predict their clinical efficacy from their pharmacologic profile. The decision regarding the use of a specific low-molecular-weight heparin should be based on the efficacy and safety data available for each product. In clinical trials comparing low-molecular-weight heparin with heparin, only enoxaparin sodium has been shown to reduce the risk of coronary events in patients with non-ST segment elevation acute coronary ischemia.
Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease. [2022]Low-molecular-weight heparins administered subcutaneously once or twice daily have been reported to be as safe and efficacious as intravenous unfractionated heparin in the treatment of acute venous thromboembolic disease.
Tinzaparin: new indication. Easier treatment of less severe pulmonary embolism. [2007](1) The standard first-line antithrombotic treatment for pulmonary embolism in patients without cardiovascular shock or marked hypotension is intravenous infusion of unfractionated heparin for a few days, followed by several months of oral anticoagulation. (2) In France, tinzaparin is the first low-molecular-weight heparin (LMWH) to be licensed specifically for treating pulmonary embolism (one subcutaneous injection daily). (3) The clinical file mainly comprises data from a comparative unblinded trial versus unfractionated heparin in 612 patients, which shows tinzaparin to have no advantage in terms of overall mortality or the incidence of bleeding. A trial comparing unfractionated heparin with another LMWH, reviparin, gave similar results. (4) In practice, tinzaparin offers the advantage over unfractionated heparin of not requiring intravenous administration. For the least severely ill patients, tinzaparin is an advance. Close laboratory monitoring of clotting factors is warranted for elderly and obese patients, and those with renal impairment. For other patients, intravenous infusion of unfractionated heparin remains the standard treatment for pulmonary embolism.
Heparin and low-molecular-weight heparin in the treatment of venous thromboembolism. [2019]Venous thromboembolism (deep vein thrombosis and pulmonary embolism) continues to constitute a major clinical challenge. Effective and safe prophylactic measures against venous thromboembolism are now available for most high risk patients. In spite of this, pulmonary embolism is responsible for approximately 150,000 to 200,000 deaths per year in the United States alone. Over the past 20 years, based on a number of high quality (Level I) clinical trials, patterns of practice with respect to the treatment of venous thromboembolism have changed dramatically. The standard treatment of venous thromboembolism has been the use of unfractionated heparin by continuous intravenous infusion, with laboratory monitoring using the activated partial thromboplastin time (APTT), with warfarin starting on day 1 or 2 and continued for 3 months. Unfractionated heparin has withstood the test of time and has been shown to be safe and effective in preventing recurrent venous thromboembolism and death in numerous clinical trials. The response of individual patients to heparin is highly variable, requiring frequent laboratory monitoring. Heparin has a number of other troublesome side effects including bleeding, heparin-induced thrombocytopenia and osteoporosis. The low-molecular-weight heparins have a number of advantages over unfractionated heparin. In particular, their increased bio-availability and prolonged half-life permit once daily subcutaneous injections and their predictable antithrombotic response based on body weight permits treatment without laboratory monitoring. Low-molecular-weight heparin in therapeutic doses causes less bleeding than unfractionated heparin and evidence is accumulating that the incidence of heparin-induced thrombocytopenia and osteoporosis are decreased as well. In individual clinical trials and meta-analyses, low-molecular-weight heparin treatment results in decreased recurrent thromboembolism, major bleeding and death when compared with unfractionated heparin in the treatment of deep vein thrombosis and pulmonary embolism. These agents have also been shown to be both effective and safe for the out-of-hospital treatment of venous thrombosis. Therefore, in many countries, low-molecular-weight heparin has replaced unfractionated heparin for the treatment of venous thromboembolism.
Treatment of acute pulmonary embolism by a low molecular weight heparin fraction. A preliminary study. [2019]We evaluated the antithrombotic efficacy of the low molecular weight heparin (LMWH) fraction PK 10169 in nine consecutive patients with acute pulmonary embolism documented by pulmonary angioscan and angiography. Therapy with PK 10169 was initiated by an i.v. bolus of 0.5 mg/kg, followed by a continuous intravenous infusion during the first 10 days; the drug was then given subcutaneously twice daily during the following 15 days. The dosage of PK 10169 was adjusted by daily measurements of anti-Xa and anti-IIa activities using amidolytic methods. For a dosage ranging from 1.4 to 4.1 mg/kg per day during the i.v. period and from 0.7 to 3.5 mg/kg per day during the s.c. period, the anti-Xa activity ranged from 4 to 8.7 PK U/ml and from 4.5 to 7.2 PK U/ml respectively. Clinical improvement was observed in all the patients and was consistent with progressive reperfusion evaluated by successive angioscans. No recurrence of pulmonary embolism occurred. No deleterious hemorrhagic side-effects were observed, even in two patients at high risk of bleeding. In this pilot study, the LMWH fraction PK 10169 proved to be an effective anticoagulant therapy during the first three weeks after pulmonary embolism in man.
Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. [2022]The standard initial treatment of hemodynamically stable patients with pulmonary embolism is intravenous unfractionated heparin, requiring laboratory monitoring and hospitalization.