Submassive Pulmonary EmbolismPhase 3ULTIMANCT01166997
ULTrasound Accelerated ThrombolysIs of PulMonAry Embolism
A Phase 3 study testing EkoSonic Endovascular System and Unfractionated heparin in people with Submassive Pulmonary Embolism, run by Boston Scientific Corporation at 10 sites in 2 countries.
Trial summary
The ULTIMA study is intended to prove that in patients with pulmonary embolism and a right ventricular end diastolic diameter to left ventricular end diastolic diameter ratio ≥1 (RV/LV ratio) will benefit from treatment with ultrasound accelerated thrombolysis (rt-PA) as compared to unfractionated heparin… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Submassive Pulmonary Embolism
- What is being tested?
- EkoSonic Endovascular System and Unfractionated heparin
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 10 sitesin 2 countries
- Study dates
- Jul 2010to May 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with acute PE symptoms < 14 days.
- Filling defect by contrast-enhanced chest CT in at least one main or proximal lower lobe pulmonary artery
- Right ventricular dysfunction confirmed by echocardiography where the RV/LV end diastolic diameter ratio is ≥ 1.0.
Who cannot join
- Age less than 18 years or greater than 80 years
- Index PE symptom duration > 14 days
- Insufficient echocardiographic image quality in the apical or subcostal four-chamber view that prohibits the measurement of the right and left ventricular end-diastolic dimensions
- Known significant bleeding risk
- Administration of thrombolytic agents, e.g., tissue plasminogen activator, streptokinase, or urokinase, within the previous 4 days
- Active bleeding
Show all 24Show fewer
- Known bleeding diathesis
- Known coagulation disorder, platelet count < 100 000/mm3, or previous use of vitamin K antagonists with INR > 2.5
- History of any intracranial or intraspinal surgery or trauma or intracranial/intraspinal bleed
- Intracranial neoplasm, arteriovenous malformation, or aneurysm
- Recent (< 3 months) GI bleeding.
- Recent (< 3 months) internal eye surgery or hemorrhagic retinopathy; recent (< 10 days) major surgery, cataract surgery, trauma, CPR, obstetrical delivery, or other invasive procedure.
- Allergy, hypersensitivity, or thrombocytopenia from heparin, rt-PA, or iodinated contrast, except for mild-moderate contrast allergies for which steroid pre-medication can be used.
- Estimated glomerular filtration rate (eGFR) < 50 ml/min as calculated by the Cockroft formula.
- Hemodynamic collapse at presentation defined as: need for cardiopulmonary resuscitation; or systolic blood pressure < 90 mm Hg for at least 15 min, or drop of systolic blood pressure by at least 40 mm Hg for at least 15 min with signs of end organ hypoperfusion (cold extremities or low urinary output < 30 mL/h or mental confusion); or need for catecholamine administration to maintain adequate organ perfusion and a systolic blood pressure of > 90 mm Hg.
- Severe hypertension on repeated readings (systolic > 180 mmHg or diastolic > 105 mmHg).
- Pregnant, lactation or parturition within the previous 30 days (positive pregnancy test, women of childbearing age must be tested).
- Participating in any other investigational drug or device study.
- Life expectancy < 90 days.
- Inability to comply with study assessments (e.g. due to geographic distance).
- Previous enrollment in this study
- Any other condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated.
- Known right-to-left shunt, for example from large patent foramen ovale or atrial septal defect
- Large (>10 mm) right atrial or right ventricular thrombus
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
Germany9 sites
Klinikum Lippe-Detmold
Detmold, 32756
Klinikum Dortmund gGmbH
Dortmund, 44137
Universitätsklinikum Carl Gustav Carus an der TU Dresden
Dresden, 01307
Universitätsklinikum der Ernst-Moritz-Arndt-Universität,
Greifswald, 17475
Universitätsklinikum Heidelberg
Heidelberg, 69120
Klinikum der Ludwig-Maximilians-Universität (LMU)
München, 81377
Christliches Krankenhaus Quakenbrueck
Quakenbrück, 49610
Helios Klinikum Siegburg
Siegburg, 53721
SRH Zentralklinikum Suhl
Suhl, 98527
Switzerland1 site
Inselspital Bern, Kliniken fur Kardiologie and Angiologie
Bern, 3010
About this study
Official title: Randomized, Controlled Study Comparing EKOS EkoSonic Ultrasound Accelerated Thrombolysis to Anticoagulation in the Treatment of Sub-massive Pulmonary Embolism
The ULTIMA study is intended to prove that in patients with pulmonary embolism and a right ventricular end diastolic diameter to left ventricular end diastolic diameter ratio ≥1 (RV/LV ratio) will benefit from treatment with ultrasound accelerated thrombolysis (rt-PA) as compared to unfractionated heparin anticoagulation. Specifically, at 24 hours the RV/LV ratio will be significantly reduced in the treatment arm compared to the control arm.
- Conditions
- Submassive Pulmonary Embolism
- Being tested
- EkoSonic Endovascular System, Unfractionated heparin
- Keywords
- Pulmonary embolism, Pulmonary thromboembolism, anticoagulation, thrombolysis, ultrasound accelerated thrombolysis
- Medical subject headings
- Pulmonary Embolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EkoSonic Endovascular SystemDevice
The EkoSonic Endovascular System will be used to deliver < 20 mg of rt-PA ( Actilyse) directly into the occlusive pulmonary thrombus.
Unfractionated heparinDrug
Intravenous unfractionated heparin used for anticoagulation treatment
| Study group | Role | What they receive |
|---|---|---|
| Ultrasound accelerated thrombolysis | Experimental | Patients in this arm will receive anti-coagulation (intravenous unfractionated heparin) plus the EkoSonic Endovascular System will be used to deliver a low dose <20mg rt-PA (Actilyse) directly into the occlusive pulmonary thrombus. Receives: Device: EkoSonic Endovascular System |
| Intravenous unfractionated heparin | Active comparator | Patients in this arm will receive the standard of care: intravenous unfractionated heparin used as anti-coagulation treatment. Receives: Drug: Unfractionated heparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction of RV/LV Ratio
Change in the end-diastolic RV/LV ratio from baseline to 24 hours by echocardiography.
Measured: 24 hours
Major Bleeding and Intracranial Bleeding at 30 Days.
Bleeding will be classified as major if it is associated with a fall in the hemoglobin level of at least 2.0 g/dl, transfusion of ≥ 2 units of red blood cells, or involvement of a critical site (e.g., intracranial, intraspinal). To aid in evaluating the relationship of bleeding events to rt-PA administration, they will also be categorized by whether they occurred within 3 days after the initiation of thrombolytic therapy.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2010 (estimated)
- Study startJul 2010
- Primary completionApr 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Submassive Pulmonary EmbolismStudies of the same condition, open and under way.
- More trials run by Boston Scientific CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Scientific Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- EKOS Corporation
- Responsible party
- Sponsor
- Investigators
- Nils Kucher, Prof Dr med, Principal investigator, Inselspital Bern, Kliniken für Angiologie und Kardiologie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01166997
- Sponsor's protocol ID
- EKOS Protocol Number 08
- Acronym
- ULTIMA
- Status last verified
- Jul 2021
- First submitted
- 15 Jul 2010
- Last updated
- 19 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Kucher N, Boekstegers P, Muller OJ, Kupatt C, Beyer-Westendorf J, Heitzer T, Tebbe U, Horstkotte J, Muller R, Blessing E, Greif M, Lange P, Hoffmann RT, Werth S, Barmeyer A, Hartel D, Grunwald H, Empen K, Baumgartner I. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2014 Jan 28;129(4):479-86. doi: 10.1161/CIRCULATIONAHA.113.005544. Epub 2013 Nov 13.
PubMed 24226805
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Controlled Study Comparing EKOS EkoSonic Ultrasound Accelerated Thrombolysis to Anticoagulation in the Treatment of Sub-massive Pulmonary Embolism
- ClinicalTrials.gov ID
- NCT01166997
- Acronym / sponsor ID
- ULTIMA / EKOS Protocol Number 08
- Conditions
- Submassive Pulmonary Embolism
- Keywords
- Pulmonary embolism, Pulmonary thromboembolism, anticoagulation, thrombolysis, ultrasound accelerated thrombolysis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Boston Scientific CorporationIndustry (pharma, biotech, devices)
- Collaborators
- EKOS Corporation
- Study start
- Jul 2010
- Primary completion
- Apr 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 21 Jul 2010 (estimated)
- Results
- Posted 18 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The ULTIMA study is intended to prove that in patients with pulmonary embolism and a right ventricular end diastolic diameter to left ventricular end diastolic diameter ratio ≥1 (RV/LV ratio) will benefit from treatment with ultrasound accelerated thrombolysis (rt-PA) as compared to unfractionated heparin anticoagulation. Specifically, at 24 hours the RV/LV ratio will be significantly reduced in the treatment arm compared to the control arm.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ultrasound accelerated thrombolysis | Experimental | Device: EkoSonic Endovascular SystemPatients in this arm will receive anti-coagulation (intravenous unfractionated heparin) plus the EkoSonic Endovascular System will be used to deliver a low dose <20mg rt-PA (Actilyse) directly into the occlusive pulmonary thrombus. |
| Intravenous unfractionated heparin | Active comparator | Drug: Unfractionated heparinPatients in this arm will receive the standard of care: intravenous unfractionated heparin used as anti-coagulation treatment. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients with acute PE symptoms < 14 days.
- Filling defect by contrast-enhanced chest CT in at least one main or proximal lower lobe pulmonary artery
- Right ventricular dysfunction confirmed by echocardiography where the RV/LV end diastolic diameter ratio is ≥ 1.0.
Key exclusion criteria (24 listed)
- Age less than 18 years or greater than 80 years
- Index PE symptom duration > 14 days
- Insufficient echocardiographic image quality in the apical or subcostal four-chamber view that prohibits the measurement of the right and left ventricular end-diastolic dimensions
- Known significant bleeding risk
- Administration of thrombolytic agents, e.g., tissue plasminogen activator, streptokinase, or urokinase, within the previous 4 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EkoSonic Endovascular SystemThe EkoSonic Endovascular System will be used to deliver < 20 mg of rt-PA ( Actilyse) directly into the occlusive pulmonary thrombus. | Device | Ultrasound accelerated thrombolysis |
| Unfractionated heparinIntravenous unfractionated heparin used for anticoagulation treatment | Drug | Intravenous unfractionated heparin |
Primary outcome
Reduction of RV/LV Ratio
Time frame: 24 hours
Change in the end-diastolic RV/LV ratio from baseline to 24 hours by echocardiography.
Major Bleeding and Intracranial Bleeding at 30 Days.
Time frame: 30 days
Bleeding will be classified as major if it is associated with a fall in the hemoglobin level of at least 2.0 g/dl, transfusion of ≥ 2 units of red blood cells, or involvement of a critical site (e.g., intracranial, intraspinal). To aid in evaluating the relationship of bleeding events to rt-PA administration, they will also be categorized by whether they occurred within 3 days after the initiation of thrombolytic therapy.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24226805Kucher N, Boekstegers P, Muller OJ, Kupatt C, Beyer-Westendorf J, Heitzer T, Tebbe U, Horstkotte J, Muller R, Blessing E, Greif M, Lange P, Hoffmann RT, Werth S, Barmeyer A, Hartel D, Grunwald H, Empen K, Baumgartner I. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2014 Jan 28;129(4):479-86. doi: 10.1161/CIRCULATIONAHA.113.005544. Epub 2013 Nov 13.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nils Kucher, Prof Dr med principal investigator
Inselspital Bern, Kliniken für Angiologie und Kardiologie
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing EkoSonic Endovascular System and Unfractionated heparin in people with Submassive Pulmonary Embolism, run by Boston Scientific Corporation at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Germany, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction of RV/LV Ratio (time frame: 24 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01166997, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2021.