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Background: Non-immunogenic staphylokinase is a modified recombinant staphylokinase with low immunogenicity, high thrombolytic activity, and fibrin selectivity., Objectives: To assess the safety and efficacy of a single intravenous bolus of non-immunogenic staphylokinase compared with those of alteplase in patients with massive pulmonary embolism and hemodynamic instability., Methods: A randomized, open-label, multicenter, parallel-group, non-inferiority trial, the FORPE (FORtelyzin Pulmionary Embolism), was conducted in Russia. A total of 310 patients aged 18 years and older with computed tomography pulmonary angiography confirmed diagnosis of massive pulmonary embolism and right ventricular dysfunction were included. The patients were randomly assigned to receive either non-immunogenic staphylokinase (15 mg) or alteplase (100 mg), both administered intravenously. The primary efficacy endpoint was death from all causes within 7 days of randomization., Results: A total of 155 patients were randomly assigned to receive non-immunogenic staphylokinase, and 155 received alteplase. In the non-immunogenic staphylokinase group, the primary efficacy endpoint was 2% in the intention-to-treat population, while in the alteplase group, it was 3% (odds ratio, 0.75; 95% CI, 0.11-4.49; P = 1.00). The difference in the primary efficacy endpoint was 0.6% (95% CI, -2.8% to 4.0%). Thus, the lower limit of the 95% CI did not cross the margin of non-inferiority. No cases of major bleeding were recorded in the non-immunogenic staphylokinase group, whereas there were 5 cases of major bleeding (3%; P = .09) in the alteplase group., Conclusion: Non-immunogenic staphylokinase was non-inferior to alteplase in patients with massive pulmonary embolism. Future observational studies are needed to assess its safety and efficacy., Competing Interests: Declaration of competing interests S.G.L. has received lectureship fees from Aspen, Bayer, Medak, Pfizer, Sanofi, Servier, SuperGene, and Takeda and declared a patent issued for a method for the treatment of patients with pulmonary embolism. S.N.T. participated in clinical trials by AstraZeneca, Novartis, Pfizer, Sanofi, Servier, and Takeda; has received lectureship fees from Akrikhin, AstraZeneca, Bayer, Boehringer Ingelheim, Berlin-Chemie AG, Gedeon Richter, Novartis, Pfizer, Sanofi, SuperGene, and Takeda; clinical research grants from Amgen, AstraZeneca, Novartis, Pfizer, and Servier. I.S.Y. has received lectureship fees from Abbott, Alfasigma, Aspen, AstraZeneca, Bayer, Boehringer Ingelheim, KRKA, Pfaizer, Sanofi, Servier, and Stada. R.M.S. has received lectureship fees from AstraZeneca, Berlin-Chemie AG, Novartis, Pfizer, Sanofi, and SuperGene. A.D.E. has received lectureship fees from AstraZeneca, Bayer, Boehringer Ingelheim, MSD, Novartis, Pfizer, Phillips, Sanofi-Aventis, Servier, and Zentiva. O.B.T. has received lectureship fees from Amgen, AstraZeneca, Generium, Novartis, Pfizer, and R-Pharm. M.P.S., A.M.S., S.V.I., and S.S.M. are employees of SuperGene. M.P.S., A.M.S., and S.S.M. declare a patent issued for a method for the treatment of patients with pulmonary embolism. E.A.P. participated in clinical trials by Biocad and has received lecture fees from Alfasigma, Bayer, and Servier. V.V.B. participated in clinical trials by AstraZeneca and has received lecture fees from Bayer, SuperGene, Pfizer, Boehringer Ingelheim, AstraZeneca, and Sanofi. S.L.K. participated in clinical trials by SuperGene and has received lecture fees from SuperGene. D.V.D. participated in clinical trials by Actelion Pharmaceuticals, Amgen, Bayer, Boehringer Ingelheim, and Novartis. V.V.K. participated in clinical trials by Boehringer Ingelheim, Generium, and Novartis and has received lecture fees from Bayer, Novartis, Pfizer, Stada, Sanofi, and Servier. V.E.O. participated in clinical trials by Boehringer Ingelheim, Novartis, and Servier and has received lecture fees from Akrikhin, AstraZeneca, and Sanofi. V.V.M. participated in clinical trials by Amgen and Pharmasyntez. All other authors declare no competing interests., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Objectives: This report describes the baseline clinical profiles and management of DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial participants and how these compare with those in other contemporary heart failure with preserved ejection fraction trials., Background: The DELIVER trial was designed to evaluate the effects of the sodium-glucose cotransporter-2 inhibitor dapagliflozin on cardiovascular death, heart failure (HF) hospitalization, or urgent HF visits in patients with HF with mildly reduced and preserved left ventricular ejection fraction (LVEF)., Methods: Adults with symptomatic HF and LVEF >40%, with or without type 2 diabetes mellitus, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and evidence of structural heart disease were randomized to dapagliflozin 10 mg once daily or matching placebo., Results: A total of 6,263 patients were randomized (mean age: 72 ± 10 years; 44% women; 45% type 2 diabetes mellitus; 45% with body mass index ≥30 kg/m 2 ; and 57% with history of atrial fibrillation or flutter). Most participants had New York Heart Association functional class II symptoms (75%). Baseline mean LVEF was 54.2 ± 8.8% and median NT-proBNP of 1,399 pg/mL (IQR: 962 to 2,210 pg/mL) for patients in atrial fibrillation/flutter compared with 716 pg/mL (IQR: 469 to 1,281 pg/mL) in those who were not. Patients in both hospitalized and ambulatory settings were enrolled, including 10% enrolled in-hospital or within 30 days of a hospitalization for HF. Eighteen percent of participants had HF with improved LVEF., Conclusions: DELIVER is the largest and broadest clinical trial of this population to date and enrolled high-risk, well-treated patients with HF with mildly reduced and preserved LVEF. (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [NCT03619213])., Competing Interests: Funding Support and Author Disclosures The DELIVER study was funded by AstraZeneca. Dr Solomon has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Mesoblast, MyoKardia, National Institutes of Health/NHLBI, Neurotronik, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, US2.AI; and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, and Sarepta. Dr Vaduganathan has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Novartis, Pharmacosmos, Relypsa, Roche Diagnostics, and Sanofi, speaker engagements with Novartis and Roche Diagnostics, and participates on clinical endpoint committees for studies sponsored by Galmed and Novartis. Dr Claggett has received consulting fees from Boehringer Ingelheim. Dr De Boer’s institution, the UMCG, has received research grants and fees (outside the submitted work) from AstraZeneca, Abbott, Boehringer Ingelheim, Cardio Pharmaceuticals Gmbh, Ionis Pharmaceuticals, Inc, Novo Nordisk, and Roche. Dr de Boer has received speaker fees from Abbott, AstraZeneca, Bayer, Novartis, and Roche (outside the submitted work). Dr DeMets has received consulting fees from Frontier Science, Actelion, Bristol Myers Squibb, Medtronic, Boston Scientific, GlaxoSmithKline, and Merck; and has received consulting fees and is the owner of DL DeMets Consulting. Dr Hernandez has received research support from American Regent, AstraZeneca, Boehringer Ingelheim, Merck, Novartis, and Verily; and has served as a consultant or on the Advisory Board for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cytokinetics, Myokardia, Merck, Novartis, and Vifor. Dr Inzucchi has served on clinical trial committees or as a consultant to AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Lexicon, Merck, Pfizer, vTv Therapeutics, Abbott, and Esperion; and has given lectures sponsored by AstraZeneca and Boehringer Ingelheim. Dr Kosiborod has received research grant support from AstraZeneca, and Boehringer Ingelheim; has served as a consultant or on an advisory board for Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion Therapeutics, Janssen, Merck (Diabetes and Cardiovascular), Novo Nordisk, Sanofi, and Vifor Pharma; has received other research support from AstraZeneca; and has received honorarium from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from AstraZeneca, Bayer, Boston Scientific, and Roche Diagnostics; has served as a consultant or on the advisory board/steering committee/executive committee for Actelion, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc, Us2.ai, Janssen Research & Development LLC, Medscape, Merck, Novartis, Novo Nordisk, Radcliffe Group Ltd, Roche Diagnostics, Sanofi, and WebMD Global LLC; and serves as the cofounder and non-executive director of Us2.ai. Dr Martinez has received personal fees from AstraZeneca. Drs Shah and Belohjavek have received either personal or institutional research support for DELIVER from AstraZeneca. Dr Chiang has received honoraria and consultation fees from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, and Sanofi. Dr Borleffs has received speaker fees and institutional research support from AstraZeneca; has received speaker fees from Novartis; and has received institutional research support from Boehringer Ingelheim. Dr Comin-Comet has received personal and institutional financial support for the DELIVER study from AstraZeneca; outside this work, he has received fees for speaking and fees for consultancy from Boehringer Ingelheim, Novartis, Orion Pharma, and Vifor Pharma; and he has received research grants from Novartis, Orion Pharma, and Vifor Pharma. Dr Dobreanu has received either personal or institutional research support for DELIVER from AstraZeneca. Dr Drozdz has received personal and institutional research support for DELIVER from AstraZeneca. Dr Fang has received either personal or institutional research support for DELIVER from AstraZeneca. Dr Gamba has received personal fees from Sanfer, Roche, Amgen, Asofarma, Sanofi, AstraZeneca, Eli Lilly, Boehringer, Bristol Myers Squibb, Bayer, Pfizer, Merck, Abbott, Silanes, Servier, Jansen Cilag, Medtronic, and Boston Scientific. Drs Al Habeeb, Han, Cabrera, Janssens, Vardeny, and Nguyen have received either personal or institutional research support for DELIVER from AstraZeneca. Dr Katova has received fees for serving as national coordinator from Novartis and AstraZeneca. Dr Kitakaze has received support for the present manuscript (funding, provision of study materials, medical writing, article processing charges, etc) from AstraZeneca, has received grants or contracts from the Japanese government through the Japan Agency for Medical Research and Development Japan Heart Foundation, and has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, Ono, Novartis, Tanabe-Mitsubishi, Japan Medical Data Center, Takeda, Pfizer, Daiichi-Sankyo, Otsuka, Sanofi, Boehringer Ingelheim, Amgen, Kowa, Toyama-Kagaku, Kureha, Viatris, and Mochida. Dr Merkely has received personal fees from AstraZeneca and Servier. Dr O’Meara has served as a consultant and speaker for AstraZeneca, Bayer, Boehringer Ingelheim, and Novartis; has served as a steering committee member or a national lead investigator with contracts between her institution (Montreal Heart Institute Research Center) and American Regent, AstraZeneca, Cytokinetics, Merck, and Novartis; and has ongoing clinical trial participation with Amgen, Abbott, American Regent, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eidos, Novartis, Merck, Pfizer, and Sanofi. Dr Kerr Saraiva has received research grant support from Pfizer, Daichii Sankyo, Sanofi, Boehringer Ingelheim, Novo Nordisk, AstraZeneca, Janssen, Amgen, and Novartis; and has received honorarium from Boehringer Ingelheim, Novo Nordisk, Astra Zeneca, and Amgen. Dr Tereshchenko has received personal fees from Servier, AstraZeneca, Pfizer, Novartis, and Boehringer Ingelheim. Dr Thierer has received support for lectures and advisory boards from AstraZeneca, Boehringer Ingelheim, and Pfizer. Dr Verma has received research grants and/or speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, EOCI Pharmacomm Ltd, HLS Therapeutics, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, PhaseBio, Sanofi, Sun Pharmaceuticals, and the Toronto Knowledge Translation Working Group; and is the President of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician organization. Drs Wilderäng, Zaozerska, Lindholm, and Petersson are employees and shareholders of AstraZeneca. Dr McMurray has received funding to his institution, Glasgow University, for his work on clinical trials, consulting, and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Cardurion, Cytokinetics, GlaxoSmithKline, Novartis, Pfizer, and Theracos; and has received personal lecture fees from the Corpus, Abbott, Hickma, Sun Pharmaceuticals, and Medsca., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)