Early switch to oral anticoagulation in patients with acute intermediate-risk pulmonary embolism (PEITHO-2): a multinational, multicentre, single-arm, phase 4 trial

doi:10.1016/S2352-3026(21)00203-9

Clinical Trial

. 2021 Sep;8(9):e627-e636.

doi: 10.1016/S2352-3026(21)00203-9. Epub 2021 Aug 4.

Early switch to oral anticoagulation in patients with acute intermediate-risk pulmonary embolism (PEITHO-2): a multinational, multicentre, single-arm, phase 4 trial

Frederikus A Klok¹, Gerrit Toenges², Anna C Mavromanoli³, Stefano Barco⁴, Walter Ageno⁵, Hélène Bouvaist⁶, Marianne Brodmann⁷, Claudio Cuccia⁸, Francis Couturaud⁹, Claudia Dellas¹⁰, Konstantinos Dimopoulos¹¹, Daniel Duerschmied¹², Klaus Empen¹³, Pompilio Faggiano¹⁴, Emile Ferrari¹⁵, Nazzareno Galiè¹⁶, Marcello Galvani¹⁷, Alexandre Ghuysen¹⁸, George Giannakoulas¹⁹, Menno V Huisman²⁰, David Jiménez²¹, Matija Kozak²², Irene Marthe Lang²³, Mareike Lankeit²⁴, Nicolas Meneveau²⁵, Thomas Münzel²⁶, Massimiliano Palazzini¹⁶, Antoniu Octavian Petris²⁷, Giancarlo Piovaccari²⁸, Aldo Salvi²⁹, Sebastian Schellong³⁰, Kai-Helge Schmidt³¹, Franck Verschuren³², Irene Schmidtmann², Guy Meyer³³, Stavros V Konstantinides³⁴; PEITHO-2 investigators

Collaborators, Affiliations

Collaborators

PEITHO-2 investigators:
Jaime Antonio, Abelaira Freire, Walter Ageno, Ibrahim Akin, Toni Anusic, Stefano Barco, Dorothea Becker, Laurent Bertoletti, Giuseppe Bettoni, Harald Binder, Marianne Brodmann, Hélène Bouvaist, Regina Carels, Claudio Cuccia, Francis Couturaud, Claudia Dellas, Giuseppe Di Pasquale, Konstantinos Dimopoulos, Daniel Dürschmied, Klaus Empen, Iolanda Enea, Pompilio Faggiano, Emile Ferrari, Joachim Ficker, Nazzareno Galiè, Marcello Galvani, Sabine Genth-Zotz, George Giannakoulas, Philippe Girard, Stanislav Gorbulev, Alexandre Ghuysen, Matthias Held, Lukas Hobohm, Menno V Huisman, David Jiménez, Frederikus A Klok, Stavros V Konstantinides, Matija Kozak, Kai Kronfeld, Irene Marthe Lang, Mareike Lankeit, Walter Lehmacher, Concepcion Patricia Lopez Miguel, Nadine Martin, Anna Mavromanoli, Nicolas Meneveau, Guy Meyer, Thomas Münzel, Massimiliano Palazzini, Roman Pareznik, Antoniu Octavian Petris, Giancarlo Piovaccari, Kurt Quitzau, Irinel Raluca Parepa, Purificacion Ramirez Martin, Marc Righini, Aldo Salvi, Sebastian Schellong, Kai-Helge Schmidt, Irene Schmidtmann, Gerrit Toenges, Silviu Bogdan Todea, Adam Torbicki, Luca Valerio, Thomas Vanassche, Franck Verschuren, Luminita Animarie Vida-Simiti, Anamaria Wolf-Pütz

Affiliations

¹ Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany; Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, Netherlands.
² Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
³ Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
⁴ Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany; Clinic of Angiology, University Hospital Zurich, Zurich, Switzerland.
⁵ Department of Medicine and Surgery, University of Insubria, Varese, Italy.
⁶ Department of Cardiology, Pôle Thorax et Vaisseaux, CHU Grenoble Alpes, La Tronche, France.
⁷ Department of Angiology, Medical University Graz, Graz, Austria.
⁸ Cardiovascular Department, Fondazione Poliambulanza, Istituto Ospedaliero, Brescia, Italy.
⁹ Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, and EA3878, FCRIN INNOVTE, Brest University, Brest, France.
¹⁰ Clinic of Paediatric Cardiology and Intensive Care, GUCH Center, University Medical Center Goettingen, Goettingen, Germany.
¹¹ Royal Brompton Hospital, and National Heart and Lung Institute, Imperial College London, London, UK.
¹² Department of Cardiology and Angiology I, University Heart Center Freiburg - Bad Krozingen, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
¹³ Department of Internal Medicine, Städtisches Klinikum Dessau, Dessau-Roßlau, Germany.
¹⁴ Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Institute of Cardiology, ASST Spedali Civili di Brescia, Brescia, Italy.
¹⁵ Service de Cardiologie, Hôpital Pasteur, Centre Hospitalier Universitaire de Nice, Nice, France.
¹⁶ DIMES, University of Bologna and IRCCS, S Orsola University Hospital, Bologna, Italy.
¹⁷ Division of Cardiology, Department of Cardiovascular Diseases, AUSL Romagna, Ospedale Morgagni-Pierantoni, Forli, Italy; Cardiovascular Research Unit, Fondazione Cardiologica Myriam Zito Sacco, Forli, Italy.
¹⁸ Emergency Care, University Hospital Centre Liège, Liège, Belgium.
¹⁹ Cardiology Department, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
²⁰ Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, Netherlands.
²¹ Department of Respiratory Diseases, Ramon y Cajal Hospital, Universidad de Alcalá, CIBER Enfermedades Respiratorias (CIBERES), Madrid, Spain.
²² Department of Vascular Diseases, University Medical Center, Ljubljana, Slovenia.
²³ Department of Cardiology, Medical University of Vienna, Vienna, Austria.
²⁴ Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany; Clinic of Cardiology and Pneumology, University Medical Center Goettingen, Goettingen, Germany; Department of Internal Medicine and Cardiology, Charité-University Medicine Berlin, Germany.
²⁵ Department of Cardiology, University Hospital Jean Minjoz, Besançon, France; EA3920, University of Burgundy Franche-Comté, Besançon, France.
²⁶ Department of Cardiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
²⁷ Grigore T Popa University of Medicine and Pharmacy Iasi, Cardiology Clinic, St Spiridon County Clinical Emergency Hospital, Iasi, Romania.
²⁸ Department of Cardiovascular Diseases, Infermi Hospital, AUSL Romagna, Rimini, Italy.
²⁹ Internal and Subintensive Medicine Department, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona, Italy.
³⁰ Department of Internal Medicine 2, Municipal Hospital Dresden, Dresden, Germany.
³¹ Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany; Department of Cardiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
³² Emergency Department, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
³³ Pulmonology and Intensive Care Service, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, Paris Descartes University, INSERM UMR S 970, and INNOVTE, Paris, France.
³⁴ Department of Cardiology, Democritus University of Thrace, Alexandroupolis, Greece; Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany. Electronic address: stavros.konstantinides@unimedizin-mainz.de.

PMID: 34363769
DOI: 10.1016/S2352-3026(21)00203-9

Clinical Trial

Early switch to oral anticoagulation in patients with acute intermediate-risk pulmonary embolism (PEITHO-2): a multinational, multicentre, single-arm, phase 4 trial

Frederikus A Klok et al. Lancet Haematol. 2021 Sep.

. 2021 Sep;8(9):e627-e636.

doi: 10.1016/S2352-3026(21)00203-9. Epub 2021 Aug 4.

Authors

Collaborators

PEITHO-2 investigators:
Jaime Antonio, Abelaira Freire, Walter Ageno, Ibrahim Akin, Toni Anusic, Stefano Barco, Dorothea Becker, Laurent Bertoletti, Giuseppe Bettoni, Harald Binder, Marianne Brodmann, Hélène Bouvaist, Regina Carels, Claudio Cuccia, Francis Couturaud, Claudia Dellas, Giuseppe Di Pasquale, Konstantinos Dimopoulos, Daniel Dürschmied, Klaus Empen, Iolanda Enea, Pompilio Faggiano, Emile Ferrari, Joachim Ficker, Nazzareno Galiè, Marcello Galvani, Sabine Genth-Zotz, George Giannakoulas, Philippe Girard, Stanislav Gorbulev, Alexandre Ghuysen, Matthias Held, Lukas Hobohm, Menno V Huisman, David Jiménez, Frederikus A Klok, Stavros V Konstantinides, Matija Kozak, Kai Kronfeld, Irene Marthe Lang, Mareike Lankeit, Walter Lehmacher, Concepcion Patricia Lopez Miguel, Nadine Martin, Anna Mavromanoli, Nicolas Meneveau, Guy Meyer, Thomas Münzel, Massimiliano Palazzini, Roman Pareznik, Antoniu Octavian Petris, Giancarlo Piovaccari, Kurt Quitzau, Irinel Raluca Parepa, Purificacion Ramirez Martin, Marc Righini, Aldo Salvi, Sebastian Schellong, Kai-Helge Schmidt, Irene Schmidtmann, Gerrit Toenges, Silviu Bogdan Todea, Adam Torbicki, Luca Valerio, Thomas Vanassche, Franck Verschuren, Luminita Animarie Vida-Simiti, Anamaria Wolf-Pütz

Affiliations

¹ Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany; Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, Netherlands.
² Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
³ Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
⁴ Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany; Clinic of Angiology, University Hospital Zurich, Zurich, Switzerland.
⁵ Department of Medicine and Surgery, University of Insubria, Varese, Italy.
⁶ Department of Cardiology, Pôle Thorax et Vaisseaux, CHU Grenoble Alpes, La Tronche, France.
⁷ Department of Angiology, Medical University Graz, Graz, Austria.
⁸ Cardiovascular Department, Fondazione Poliambulanza, Istituto Ospedaliero, Brescia, Italy.
⁹ Département de Médecine Interne et Pneumologie, Centre Hospitalo-Universitaire de Brest, and EA3878, FCRIN INNOVTE, Brest University, Brest, France.
¹⁰ Clinic of Paediatric Cardiology and Intensive Care, GUCH Center, University Medical Center Goettingen, Goettingen, Germany.
¹¹ Royal Brompton Hospital, and National Heart and Lung Institute, Imperial College London, London, UK.
¹² Department of Cardiology and Angiology I, University Heart Center Freiburg - Bad Krozingen, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
¹³ Department of Internal Medicine, Städtisches Klinikum Dessau, Dessau-Roßlau, Germany.
¹⁴ Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Institute of Cardiology, ASST Spedali Civili di Brescia, Brescia, Italy.
¹⁵ Service de Cardiologie, Hôpital Pasteur, Centre Hospitalier Universitaire de Nice, Nice, France.
¹⁶ DIMES, University of Bologna and IRCCS, S Orsola University Hospital, Bologna, Italy.
¹⁷ Division of Cardiology, Department of Cardiovascular Diseases, AUSL Romagna, Ospedale Morgagni-Pierantoni, Forli, Italy; Cardiovascular Research Unit, Fondazione Cardiologica Myriam Zito Sacco, Forli, Italy.
¹⁸ Emergency Care, University Hospital Centre Liège, Liège, Belgium.
¹⁹ Cardiology Department, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
²⁰ Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, Netherlands.
²¹ Department of Respiratory Diseases, Ramon y Cajal Hospital, Universidad de Alcalá, CIBER Enfermedades Respiratorias (CIBERES), Madrid, Spain.
²² Department of Vascular Diseases, University Medical Center, Ljubljana, Slovenia.
²³ Department of Cardiology, Medical University of Vienna, Vienna, Austria.
²⁴ Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany; Clinic of Cardiology and Pneumology, University Medical Center Goettingen, Goettingen, Germany; Department of Internal Medicine and Cardiology, Charité-University Medicine Berlin, Germany.
²⁵ Department of Cardiology, University Hospital Jean Minjoz, Besançon, France; EA3920, University of Burgundy Franche-Comté, Besançon, France.
²⁶ Department of Cardiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
²⁷ Grigore T Popa University of Medicine and Pharmacy Iasi, Cardiology Clinic, St Spiridon County Clinical Emergency Hospital, Iasi, Romania.
²⁸ Department of Cardiovascular Diseases, Infermi Hospital, AUSL Romagna, Rimini, Italy.
²⁹ Internal and Subintensive Medicine Department, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona, Italy.
³⁰ Department of Internal Medicine 2, Municipal Hospital Dresden, Dresden, Germany.
³¹ Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany; Department of Cardiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
³² Emergency Department, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
³³ Pulmonology and Intensive Care Service, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, Paris Descartes University, INSERM UMR S 970, and INNOVTE, Paris, France.
³⁴ Department of Cardiology, Democritus University of Thrace, Alexandroupolis, Greece; Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany. Electronic address: stavros.konstantinides@unimedizin-mainz.de.

PMID: 34363769
DOI: 10.1016/S2352-3026(21)00203-9

Abstract

Background: Current guidelines recommend a risk-adjusted treatment strategy for the management of acute pulmonary embolism. This is a particular patient category for whom optimal treatment (anticoagulant treatment, reperfusion strategies, and duration of hospitalisation) is currently unknown. We investigated whether treatment of acute intermediate-risk pulmonary embolism with parenteral anticoagulation for a short period of 72 h, followed by a switch to a direct oral anticoagulant (dabigatran), is effective and safe.

Methods: We did a multinational, multicentre, single-arm, phase 4 trial at 42 hospitals in Austria, Belgium, France, Germany, Italy, Netherlands, Romania, Slovenia, and Spain. Adult patients (aged ≥18 years) with symptomatic intermediate-risk pulmonary embolism, with or without deep-vein thrombosis, were enrolled. Patients received parenteral low-molecular-weight or unfractionated heparin for 72 h after diagnosis of pulmonary embolism before switching to oral dabigatran 150 mg twice per day following a standard clinical assessment. The primary outcome was recurrent symptomatic venous thromboembolism or pulmonary embolism-related death within 6 months. The primary and safety outcomes were assessed in the intention-to-treat population. The study was terminated early, as advised by the data safety and monitoring board, following sample size adaptation after the predefined interim analysis on Dec 18, 2018. This trial is registered with the EU Clinical Trials Register (EudraCT 2015-001830-12) and ClinicalTrials.gov (NCT02596555).

Findings: Between Jan 1, 2016, and July 31, 2019, 1418 patients with pulmonary embolism were screened, of whom 402 were enrolled and were included in the intention-to-treat analysis (median age was 69·5 years [IQR 60·0-78·0); 192 [48%] were women and 210 [52%] were men). Median follow-up was 217 days (IQR 210-224) and 370 (92%) patients adhered to the protocol. The primary outcome occurred in seven (2% [upper bound of right-sided 95% CI 3]; p<0·0001 for rejecting the null hypothesis) patients, with all events occurring in those with intermediate-high-risk pulmonary embolism (seven [3%; upper bound of right-sided 95% CI 5] of 283). At 6 months, 11 (3% [95% CI 1-5]) of 402 patients had at least one major bleeding event and 16 (4% [2-6]) had at least one clinically relevant non-major bleeding event; the only fatal haemorrhage occurred in one (<1%) patient before the switch to dabigatran.

Interpretation: A strategy of early switch from heparin to dabigatran following standard clinical assessment was effective and safe in patients with intermediate-risk pulmonary embolism. Our results can help to refine guideline recommendations for the initial treatment of acute intermediate-risk pulmonary embolism, optimising the use of resources and avoiding extended hospitalisation.

Funding: German Federal Ministry of Education and Research, University Medical Center Mainz, and Boehringer Ingelheim.

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Conflict of interest statement

Declaration of interests FAK reports research grants from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Merck Sharpe & Dohme, the Netherlands Organisation for Health Research and Development, Actelion, the Dutch Heart foundation, and the Dutch Thrombosis Association, all outside the submitted work. SB reports congress and travel payments from Daiichi Sankyo and Bayer; honoraria from BTG Pharmaceuticals, Boston Scientific, Bayer HealthCare, and LeoPharma; and institutional grants from Sanofi, all outside the submitted work. WA reports research support from Bayer, and participating in advisory boards for Bayer, Boehringer Ingelheim, Daiichi Sankyo, Portola, Janssen, Aspen, and Sanofi all outside the submitted work. MB reports consulting and speaker fees from Bayer Healthcare, Daiichi Sankyo, and Sanofi Aventis outside the submitted work. FC reports research grant support from Bristol-Myers Squibb-Pfizer Alliance; fees for board memberships or symposia from Bayer, Bristol-Myers Squibb-Pfizer Alliance, and Astra Zeneca; and travel support from Bayer, Bristol-Myers Squibb-Pfizer Alliance, Leo Pharma, and Actelion all outside the submitted work. KD reports unrestricted research support and speaker or consultant fees from Janssen outside the submitted work. DD reports speaker's honoraria from Bayer Vital, Daiichi Sankyo, and Bristol-Myers Squibb-Pfizer Alliance; and consulting fees from Bayer Vital and Daiichi Sankyo all outside the submitted work. KE reports lecture fees from AstraZeneca, Bayer Vital, Berlin Chemie, Boehringer Ingelheim, and Novartis; and consulting fees from Bayer Vital, Boehringer Ingelheim, Novartis, and Novo Nordisk all outside the submitted work. GG reports personal fees or research grants, or both, from Bayer, Boehringer Ingelheim, Leo, Merck Sharpe & Dohme, and Pfizer outside the submitted work. MVH reports grants from the ZonMW Dutch Healthcare Fund; and grants and personal fees to the Leiden University Medical Center from Boehringer Ingelheim, Bristol-Myers Squibb-Pfizer Alliance, Bayer Health Care, Aspen, and Daiichi Sankyo, all outside the submitted work. DJ reports serving as an advisor or consultant for Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Leo Pharma, Pfizer, ROVI, and Sanofi; serving as a speaker or a member of a speakers' bureau for Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Leo Pharma, ROVI, and Sanofi; and receiving grants for clinical research from Daiichi Sankyo, Sanofi, and ROVI all outside the submitted work. MK reports speaker fees from Pfizer, Boehringer Ingelheim, and Bayer outside the submitted work. IML reports receiving consulting fees and research grants from, and being a member of scientific advisory boards for AOPOrphan Pharmaceuticals, Actelion-Janssen, Merck Sharpe & Dohme, United Therapeutics, Medtronic, Neutrolis, and Ferrer, in addition to being an investigator in trials involving these companies. ML reports consultant and speaker fees from Actelion, Bayer, Thermo Fisher Scientific, Daiichi Sankyo, Merck Sharpe & Dohme, and Bristol-Myers Squibb-Pfizer Alliance; and project funding from Thermo Fisher Scientific all outside the submitted work. NM reports consulting fees, speaker fees, and project funding from Bayer and Bristol-Myers Squibb-Pfizer Alliance; speaker fees from AstraZeneca and Boehringer Ingelheim; and consulting fees from Abbott and Terumo all outside the submitted work. AOP reports speaker fees from SC Pfizer Romania, Servier Pharma, Novartis Pharma Services Romania, Bayer, and SC Sanience outside the submitted work. AS reports consulting fees from Pfizer outside the submitted work. SS reports consulting fees and speaker fees from Aspen and Boehringer Ingelheim; speaker fees from Bayer and Daiichi Sankyo; and project funding and speaker fees from Bristol-Myers Squibb-Pfizer Alliance all outside the submitted work. K-HS reports speaker and consulting fees from Merck Sharpe & Dohme, Janssen-Cilag, and Abbott outside the submitted work. FV reports research grants from Daiichi Sanyo, Boehringer-Ingelheim, Radiometer, and Biomerieux, outside the submitted work. SVK reports institutional research grants and personal consultancy or speaker fees from Actelion/Janssen, Bayer, Daiichi Sankyo, and Boston Scientific; institutional research grants from Boehringer Ingelheim and Servier; and personal consultancy or speaker fees from Bristol-Myers Squibb-Pfizer Alliance and Novartis all outside the submitted work. All other authors declare no competing interests.

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Mavromanoli AC, Barco S, Ageno W, Bouvaist H, Brodmann M, Cuccia C, Couturaud F, Dellas C, Dimopoulos K, Duerschmied D, Empen K, Faggiano P, Ferrari E, Galiè N, Galvani M, Ghuysen A, Giannakoulas G, Huisman MV, Jiménez D, Kozak M, Lang IM, Meneveau N, Münzel T, Palazzini M, Petris AO, Piovaccari G, Salvi A, Schellong S, Schmidt KH, Verschuren F, Schmidtmann I, Toenges G, Klok FA, Konstantinides SV; PEITHO-2 Investigators. Mavromanoli AC, et al. Clin Res Cardiol. 2023 Oct;112(10):1372-1381. doi: 10.1007/s00392-022-02138-4. Epub 2022 Dec 21. Clin Res Cardiol. 2023. PMID: 36539534 Free PMC article. Clinical Trial.
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Pruszczyk P, Klok FA, Kucher N, Roik M, Meneveau N, Sharp ASP, Nielsen-Kudsk JE, Obradović S, Barco S, Giannini F, Stefanini G, Tarantini G, Konstantinides S, Dudek D. Pruszczyk P, et al. EuroIntervention. 2022 Oct 7;18(8):e623-e638. doi: 10.4244/EIJ-D-22-00246. EuroIntervention. 2022. PMID: 36112184 Free PMC article.

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Early switch to oral anticoagulation in patients with acute intermediate-risk pulmonary embolism (PEITHO-2): a multinational, multicentre, single-arm, phase 4 trial

Collaborators

Affiliations

Early switch to oral anticoagulation in patients with acute intermediate-risk pulmonary embolism (PEITHO-2): a multinational, multicentre, single-arm, phase 4 trial

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Conflict of interest statement

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