Clinical trial NCT04790370: Ultrasound-facilitated, Catheter-directed, Thrombolysis in Intermediate-high Risk Pulmonary Embolism
Official title: A Randomized Trial of Ultrasound-facilitated, Catheter-directed, Thrombolysis Versus Anticoagulation for Acute Intermediate-high Risk Pulmonary Embolism: The Higher-risk Pulmonary Embolism Thrombolysis Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Pulmonary Embolism
Keywords: Acute intermediate-high risk pulmonary embolism
Ultrasound-facilitated, catheter-directed thrombolysis
Thrombolysis
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
Collaborators: name: National PERT Consortium, Inc.
name: University Medical Center Mainz
First posted: 2021-03-10
Enrollment: 544
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1 randomization
Primary purpose: TREATMENT

Brief summary: There are many available treatments for pulmonary embolism (PE), but the best treatment for this condition is not known. The HI-PEITHO study will compare two treatment options that are both available on the market for the treatment of PE.

Patients will be randomized 1:1 to receive either blood thinners (anticoagulation) or blood thinners (anticoagulation) in combination with a device called the EkoSonicTM Endovascular device to dissolve blood clots. Patients will be followed for 12 months after randomization and have assessments while in the hospital as well as at 7 days, 30 days, 6 months and 12 months after randomization. The study will try to find out if one of these treatments is better than the other at reducing the risk of death and other serious problems.

Detailed description: This study will assess whether ultrasound-facilitated, catheter-directed thrombolysis and standard anticoagulation are associated with a significant reduction in the composite outcome of pulmonary embolism (PE)-related mortality, cardiorespiratory decompensation or collapse, or nonfatal symptomatic and objectively confirmed recurrence of PE compared to anticoagulation alone within seven days of randomization

The HI-PEITHO study has been designed to address the important gaps in clinical evidence by comparing the clinical benefit of the ultrasound-facilitated local delivery of a low dose thrombolytic agent and anticoagulation with those of anticoagulation alone in patients with intermediate-high risk PE at a higher estimated risk of early decompensation based on clinical parameters at presentation.

This study has a focus on improving the safety of thrombolysis and advancing the concept of intermediate-high risk and the PE severity criteria, to better identify patients who may clinically benefit from thrombolysis.

The results of this study will contribute further evidence to the existing data on the treatment and outcomes of acute, intermediate-high risk PE and provide controlled data related to catheter-based interventions.

Data will be entered by the site into an electronic database. The database will include data checks to compare data entered into the database against predefined rules for ranges and consistency with other data fields in the database.

Site monitoring will take place with source data verification to assess the accuracy and completeness of registry data by comparing the data to medical records and study assessments.

Eligibility criteria: Inclusion Criteria:

* Age 18-80 years, inclusive
* Objectively confirmed acute PE, based on computed tomography pulmonary angiography (CTPA) showing a filling defect in at least one main or proximal lobar pulmonary artery
* Elevated risk of early death/hemodynamic collapse, indicated by at least two of the following new-onset clinical criteria:

  1. ECG-documented tachycardia with heart rate ≥100 beats per minute, not due to hypovolemia, arrhythmia, or sepsis;
  2. SBP ≤ 110 mm Hg for at least 15 minutes;
  3. respiratory rate \> 20 x min-1 or oxygen saturation on pulse oximetry (SpO2) \< 90% (or partial arterial oxygen pressure \< 60 mmHg) at rest while breathing room air;
* Right-to-left ventricular (RV/LV) diameter ratio ≥ 1.0 on CTPA
* Serum troponin I or T levels above the upper limit of normal
* Signed informed consent

Exclusion Criteria:

* Hemodynamic instability\*, i.e. at least one of the following present:

  1. cardiac arrest or need for cardiopulmonary resuscitation;
  2. need for ECMO, or ECMO initiated before randomization
  3. PE-related shock, defined as: (i) SBP \< 90 mmHg, or vasopressors required to achieve SBP ≥ 90 mmHg, despite an adequate volume status; and (ii) end-organ hypoperfusion (altered mental status; oliguria/anuria; increased serum lactate);
  4. isolated persistent hypotension (SBP \< 90 mmHg, or a systolic pressure drop by at least 40 mmHg for at least 15 minutes), not caused by new-onset arrhythmia, hypovolemia, or sepsis \* Patients who presented with temporary need for fluid resuscitation and/or low-dose catecholamines may be included, provided that they could be stabilized within 2 hours of admission and maintain SBP of ≥ 90 mmHg and adequate organ perfusion without catecholamine infusion.
* Need for admission to an intensive care unit for a reason other than the index PE episode. NB: Patients who test positive for SARS-CoV-2 can be enrolled where the investigator believes that the pulmonary embolism is the dominant pathology in the patient's clinical presentation and qualifying cardiorespiratory parameters.
* Temperature above 39 degrees C / 102.2 degrees F
* Logistical reasons limiting the rapid availability of interventional procedures to treat acute PE (e.g., during the outbreak of an epidemic)
* Index PE symptom duration \> 14 days
* Active bleeding
* History of intracranial or intraocular bleeding at any time
* Stroke or transient ischemic attack within the past 6 months, or previous stroke at any time if associated with permanent disability
* Central nervous system neoplasm, or metastatic cancer
* Major neurologic, ophthalmologic, abdominal, cardiac, thoracic, vascular or orthopedic surgery or trauma (including syncope-associated with head strike or skeletal fracture) within the past 3 weeks
* Platelet count \< 100 x 109 x L-1
* Patients who have received a once-daily therapeutic dose of LMWH or a therapeutic dose of fondaparinux within 24 hours prior to randomization
* Patients who have received one of the direct oral anticoagulants apixaban or rivaroxaban within 12 hours prior to randomization
* Patients who have received one of the direct oral anticoagulants dabigatran or edoxaban for the index PE episode, as these drugs are not approved for patients who have not received heparin for at least 5 days
* Administration of a thrombolytic agent or a glycoprotein IIb/IIIa receptor antagonist during the current hospital stay and/or within 30 days, for any reason
* Chronic treatment with antiplatelet agents other than low-dose acetylsalicylic acid or clopidogrel 75 mg once daily (but not both). Dual antiplatelet therapy is excluded.
* Chronic treatment with a direct oral anticoagulant (apixaban, dabigatran, edoxaban or rivaroxaban)
* Chronic treatment with a vitamin K antagonist, or known coagulopathy including severe hepatic dysfunction, with an International Normalized Ratio (INR) \> 1.5
* Pregnancy or lactation
* Previous inclusion in the study
* Known hypersensitivity to alteplase, LMWH or UFH, or to any of the excipients
* Life expectancy less than 6 months

Primary outcomes:
measure: PE-related mortality
timeFrame: Within seven days of randomization
measure: PE recurrence
timeFrame: Within seven days of randomization
measure: Cardiorespiratory decompensation or collapse
timeFrame: Within seven days of randomization
Secondary outcomes:
Other outcomes:
measure: Change in the RV-to-LV diameter ratio as measured by echocardiography
timeFrame: Between baseline and 48±6 hours
measure: PE-related death
timeFrame: Within 7 days
measure: Cardiorespiratory decompensation
timeFrame: Within 7 days
measure: Placement on ECMO or mechanical ventilation
timeFrame: Within 7 days
measure: GUSTO major (moderate and severe) bleeding
timeFrame: Within 7 days
measure: International Society on Thrombosis and Hemostasis (ISTH) major bleeding
timeFrame: Within 7 days, 30 days, and 6 months
measure: Ischemic or hemorrhagic stroke
timeFrame: Within 7 days and 30 days
measure: All-cause mortality
timeFrame: Within 7 days, 30 days, 6 months, and 12 months
measure: Serious adverse events
timeFrame: Within 30 days
measure: All-cause mortality, cardiorespiratory collapse or recurrence of PE
timeFrame: Within 30 days
measure: Symptomatic PE recurrence
timeFrame: Within 30 days and 6 months
measure: Change from baseline in RV dysfunction on echocardiography
timeFrame: 6 months
measure: Duration of hospitalization for the index PE event
timeFrame: Within 30 days
measure: Duration of stay at the intensive, intermediate or coronary care unit during hospitalization for the index PE event
timeFrame: Within 30 days
measure: Functional status as measured by World Health Organization (WHO) functional class
timeFrame: Up to 7 days, 30 days, 6 and 12 months
measure: Functional status as measured by 6-Minute Walk Test (6MWT)
timeFrame: 30 days, 6 and 12 months
measure: Functional status as measured by Post-Venous Thromboembolism Functional Status (PVFS) scale
timeFrame: 30 days, 6 and 12 months
measure: Quality of life using PEmb-QOL
timeFrame: 6 and 12 months
measure: Quality of life using SF-36
timeFrame: 6 and 12 months
measure: Quality of life using EQ-5D scale
timeFrame: 6 and 12 months
measure: Diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH)
timeFrame: Within 12 months
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Cedars - Sinai Medical Center
state: California
city: Newark
country: United States
facility: Christiana Hospital
state: Delaware
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Downers Grove
country: United States
facility: Advocate Good Samaritan Hospital
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Heart Center of Indiana
state: Indiana
city: Merrillville
country: United States
facility: Methodist Hospitals
state: Indiana
city: Louisville
country: United States
facility: Jewish Hospital
state: Kentucky
city: Lousville
country: United States
facility: Baptist Health East Louisville
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Hospitals
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Detroit
country: United States
facility: St. John Hospital & Medical Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Foundation
state: Minnesota
city: Tupelo
country: United States
facility: North Mississippi Medical Center
state: Mississippi
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Camden
country: United States
facility: Cooper Hospital - University Medical Center
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital
state: New York
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Kettering
country: United States
facility: Kettering Health
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Science Center
state: Oklahoma
city: Kingsport
country: United States
facility: Wellmont Holston Valley Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Seton Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Sugarland Hospital
state: Texas
city: Plano
country: United States
facility: The Heart Hospital Baylor Plano
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin Hospitals
state: Wisconsin
city: Innsbruck
country: Austria
facility: A.o. LKH Univ.-Kliniken Innsbruck
city: St. Pölten
country: Austria
facility: Universitätsklinikum St. Pölten
city: Vienna
country: Austria
facility: Austria Klinik Ottakring Vienna
city: Wien
country: Austria
facility: Allgemeines Krankenhaus AKH
city: Besançon
country: France
facility: CHU de Besancon
city: Marseille
country: France
facility: Hopital Nord de Marseille
city: Nîmes
country: France
facility: CHU (Nimes Cedex)
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou (HEGP)
city: Aachen
country: Germany
facility: Uniklinik Aachen
city: Bielefeld
country: Germany
facility: Klinikum Bielefeld
city: Bonn
country: Germany
facility: GFO Kliniken Bonn
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz
city: Coburg
country: Germany
facility: Klinikum Coburg GmbH
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
city: Immenstädt
country: Germany
facility: Klinik Immenstadt
city: Lübeck
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein
city: Mainz
country: Germany
facility: Johannes Gutenberg Universitaet Mainz
city: Munich
country: Germany
facility: Klinikum Rechts der Isar
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Würzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Galway
country: Ireland
facility: University Hospital Galway
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum
city: Kraków
country: Poland
facility: John Paul II Hospital
city: Poznań
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Poznaniu
city: Warsaw
country: Poland
facility: Medical University of Warsaw
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Zürich
country: Switzerland
facility: University Hospital Zurich
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: London
country: United Kingdom
facility: Guys and St. Thomas NHS Foundation Trust
city: London
country: United Kingdom
facility: The Royal Free Hospital
city: Middlesex
country: United Kingdom
facility: Northwick Park Hospital
Study officials:
affiliation: University Medical Center Mainz, Mainz, Germany
name: Stavros Konstantinides, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital, Boston, Massachusetts, USA
name: Kenneth Rosenfield, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Barco S, Vicaut E, Klok FA, Lankeit M, Meyer G, Konstantinides SV; PEITHO Investigators. Improved identification of thrombolysis candidates amongst intermediate-risk pulmonary embolism patients: implications for future trials. Eur Respir J. 2018 Jan 18;51(1):1701775. doi: 10.1183/13993003.01775-2017. Print 2018 Jan. No abstract available.
citation: Marti C, John G, Konstantinides S, Combescure C, Sanchez O, Lankeit M, Meyer G, Perrier A. Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis. Eur Heart J. 2015 Mar 7;36(10):605-14. doi: 10.1093/eurheartj/ehu218. Epub 2014 Jun 10.
citation: Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, Huisman M, King CS, Morris TA, Sood N, Stevens SM, Vintch JRE, Wells P, Woller SC, Moores L. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016 Feb;149(2):315-352. doi: 10.1016/j.chest.2015.11.026. Epub 2016 Jan 7.
citation: Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, Jenkins JS, Kline JA, Michaels AD, Thistlethwaite P, Vedantham S, White RJ, Zierler BK; American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; American Heart Association Council on Peripheral Vascular Disease; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011 Apr 26;123(16):1788-830. doi: 10.1161/CIR.0b013e318214914f. Epub 2011 Mar 21.
citation: Becattini C, Agnelli G, Lankeit M, Masotti L, Pruszczyk P, Casazza F, Vanni S, Nitti C, Kamphuisen P, Vedovati MC, De Natale MG, Konstantinides S. Acute pulmonary embolism: mortality prediction by the 2014 European Society of Cardiology risk stratification model. Eur Respir J. 2016 Sep;48(3):780-6. doi: 10.1183/13993003.00024-2016. Epub 2016 May 12.
citation: Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, Bluhmki E, Bouvaist H, Brenner B, Couturaud F, Dellas C, Empen K, Franca A, Galie N, Geibel A, Goldhaber SZ, Jimenez D, Kozak M, Kupatt C, Kucher N, Lang IM, Lankeit M, Meneveau N, Pacouret G, Palazzini M, Petris A, Pruszczyk P, Rugolotto M, Salvi A, Schellong S, Sebbane M, Sobkowicz B, Stefanovic BS, Thiele H, Torbicki A, Verschuren F, Konstantinides SV; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014 Apr 10;370(15):1402-11. doi: 10.1056/NEJMoa1302097.
citation: Bajaj NS, Kalra R, Arora P, Ather S, Guichard JL, Lancaster WJ, Patel N, Raman F, Arora G, Al Solaiman F, Clark DT 3rd, Dell'Italia LJ, Leesar MA, Davies JE, McGiffin DC, Ahmed MI. Catheter-directed treatment for acute pulmonary embolism: Systematic review and single-arm meta-analyses. Int J Cardiol. 2016 Dec 15;225:128-139. doi: 10.1016/j.ijcard.2016.09.036. Epub 2016 Sep 20.
citation: 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.
citation: Piazza G, Hohlfelder B, Jaff MR, Ouriel K, Engelhardt TC, Sterling KM, Jones NJ, Gurley JC, Bhatheja R, Kennedy RJ, Goswami N, Natarajan K, Rundback J, Sadiq IR, Liu SK, Bhalla N, Raja ML, Weinstock BS, Cynamon J, Elmasri FF, Garcia MJ, Kumar M, Ayerdi J, Soukas P, Kuo W, Liu PY, Goldhaber SZ; SEATTLE II Investigators. A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study. JACC Cardiovasc Interv. 2015 Aug 24;8(10):1382-1392. doi: 10.1016/j.jcin.2015.04.020.
citation: Kuo WT, Banerjee A, Kim PS, DeMarco FJ Jr, Levy JR, Facchini FR, Unver K, Bertini MJ, Sista AK, Hall MJ, Rosenberg JK, De Gregorio MA. Pulmonary Embolism Response to Fragmentation, Embolectomy, and Catheter Thrombolysis (PERFECT): Initial Results From a Prospective Multicenter Registry. Chest. 2015 Sep;148(3):667-673. doi: 10.1378/chest.15-0119.
citation: Tapson VF, Sterling K, Jones N, Elder M, Tripathy U, Brower J, Maholic RL, Ross CB, Natarajan K, Fong P, Greenspon L, Tamaddon H, Piracha AR, Engelhardt T, Katopodis J, Marques V, Sharp ASP, Piazza G, Goldhaber SZ. A Randomized Trial of the Optimum Duration of Acoustic Pulse Thrombolysis Procedure in Acute Intermediate-Risk Pulmonary Embolism: The OPTALYSE PE Trial. JACC Cardiovasc Interv. 2018 Jul 23;11(14):1401-1410. doi: 10.1016/j.jcin.2018.04.008.
citation: Steering Committee. Single-bolus tenecteplase plus heparin compared with heparin alone for normotensive patients with acute pulmonary embolism who have evidence of right ventricular dysfunction and myocardial injury: rationale and design of the Pulmonary Embolism Thrombolysis (PEITHO) trial. Am Heart J. 2012 Jan;163(1):33-38.e1. doi: 10.1016/j.ahj.2011.10.003.
citation: Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011 Jun 14;123(23):2736-47. doi: 10.1161/CIRCULATIONAHA.110.009449. No abstract available.
citation: GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med. 1993 Sep 2;329(10):673-82. doi: 10.1056/NEJM199309023291001.
citation: Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.
citation: Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, Solomon SD, Louie EK, Schiller NB. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010 Jul;23(7):685-713; quiz 786-8. doi: 10.1016/j.echo.2010.05.010. No abstract available.
citation: Liu VX, Lu Y, Carey KA, Gilbert ER, Afshar M, Akel M, Shah NS, Dolan J, Winslow C, Kipnis P, Edelson DP, Escobar GJ, Churpek MM. Comparison of Early Warning Scoring Systems for Hospitalized Patients With and Without Infection at Risk for In-Hospital Mortality and Transfer to the Intensive Care Unit. JAMA Netw Open. 2020 May 1;3(5):e205191. doi: 10.1001/jamanetworkopen.2020.5191.
citation: Smith GB, Prytherch DR, Meredith P, Schmidt PE, Featherstone PI. The ability of the National Early Warning Score (NEWS) to discriminate patients at risk of early cardiac arrest, unanticipated intensive care unit admission, and death. Resuscitation. 2013 Apr;84(4):465-70. doi: 10.1016/j.resuscitation.2012.12.016. Epub 2013 Jan 4.
citation: Quiroz R, Kucher N, Schoepf UJ, Kipfmueller F, Solomon SD, Costello P, Goldhaber SZ. Right ventricular enlargement on chest computed tomography: prognostic role in acute pulmonary embolism. Circulation. 2004 May 25;109(20):2401-4. doi: 10.1161/01.CIR.0000129302.90476.BC. Epub 2004 May 17.
citation: Stein PD, Matta F, Yaekoub AY, Goodman LR, Sostman HD, Weg JG, Hales CA, Hull RD, Leeper KV Jr, Beemath A, Saeed IM, Woodard PK. Reconstructed 4-chamber views compared with axial imaging for assessment of right ventricular enlargement on CT pulmonary angiograms. J Thromb Thrombolysis. 2009 Oct;28(3):342-7. doi: 10.1007/s11239-009-0331-5. Epub 2009 Mar 27.
citation: ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002 Jul 1;166(1):111-7. doi: 10.1164/ajrccm.166.1.at1102. No abstract available.
citation: Klok FA, Cohn DM, Middeldorp S, Scharloo M, Buller HR, van Kralingen KW, Kaptein AA, Huisman MV. Quality of life after pulmonary embolism: validation of the PEmb-QoL Questionnaire. J Thromb Haemost. 2010 Mar;8(3):523-32. doi: 10.1111/j.1538-7836.2009.03726.x. Epub 2009 Dec 15.
citation: Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992 Jun;30(6):473-83.
citation: Burnett AE, Mahan CE, Vazquez SR, Oertel LB, Garcia DA, Ansell J. Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment. J Thromb Thrombolysis. 2016 Jan;41(1):206-32. doi: 10.1007/s11239-015-1310-7.
citation: Cech DJ, Martin ST. Evaluation of function, activity, and participation. Functional Movement Development Across the Life Span (Third Edition), 2012.
citation: Saris-Baglama RN, Dewey CJ, Chisholm GB, et al. QualityMetric health outcomes™ scoring software 4.0. Lincoln, RI: QualityMetric Incorporated, 2010, p. 138.
citation: Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, Huisman MV, Humbert M, Jennings CS, Jimenez D, Kucher N, Lang IM, Lankeit M, Lorusso R, Mazzolai L, Meneveau N, Ni Ainle F, Prandoni P, Pruszczyk P, Righini M, Torbicki A, Van Belle E, Zamorano JL; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020 Jan 21;41(4):543-603. doi: 10.1093/eurheartj/ehz405. No abstract available.
citation: Klok FA, Piazza G, Sharp ASP, Ni Ainle F, Jaff MR, Chauhan N, Patel B, Barco S, Goldhaber SZ, Kucher N, Lang IM, Schmidtmann I, Sterling KM, Becker D, Martin N, Rosenfield K, Konstantinides SV. Ultrasound-facilitated, catheter-directed thrombolysis vs anticoagulation alone for acute intermediate-high-risk pulmonary embolism: Rationale and design of the HI-PEITHO study. Am Heart J. 2022 Sep;251:43-53. doi: 10.1016/j.ahj.2022.05.011. Epub 2022 May 16.