{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T03:06:48Z","timestamp":1785294408109,"version":"3.55.0"},"reference-count":24,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,24]],"date-time":"2022-09-24T00:00:00Z","timestamp":1663977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Leo-Pharma","award":["IIS-INNOHEP-2208"],"award-info":[{"award-number":["IIS-INNOHEP-2208"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Hospitalized patients with COVID-19 are at increased risk of thrombosis, acute respiratory distress syndrome and death. The optimal dosage of thromboprophylaxis is unknown. The aim was to evaluate the efficacy and safety of tinzaparin in prophylactic, intermediate, and therapeutic doses in non-critical patients admitted for COVID-19 pneumonia. PROTHROMCOVID is a randomized, unblinded, controlled, multicenter trial enrolling non-critical, hospitalized adult patients with COVID-19 pneumonia. Patients were randomized to prophylactic (4500 IU), intermediate (100 IU\/kg), or therapeutic (175 IU\/kg) groups. All tinzaparin doses were administered once daily during hospitalization, followed by 7 days of prophylactic tinzaparin at discharge. The primary efficacy outcome was a composite endpoint of symptomatic systemic thrombotic events, need for invasive or non-invasive mechanical ventilation, or death within 30 days. The main safety outcome was major bleeding at 30 days. Of the 311 subjects randomized, 300 were included in the prespecified interim analysis (mean [SD] age, 56.7 [14.6] years; males, 182 [60.7%]). The composite endpoint at 30 days from randomization occurred in 58 patients (19.3%) of the total population; 19 (17.1 %) in the prophylactic group, 20 (22.1%) in the intermediate group, and 19 (18.5%) in the therapeutic dose group (p = 0.72). No major bleeding event was reported; non-major bleeding was observed in 3.7% of patients, with no intergroup differences. Due to these results and the futility analysis, the trial was stopped. In non-critically ill COVID-19 patients, intermediate or full-dose tinzaparin compared to standard prophylactic doses did not appear to affect the risk of thrombotic event, non-invasive ventilation, or mechanical ventilation or death. Trial RegistrationClinicalTrials.gov Identifier (NCT04730856). Edura-CT registration number: 2020-004279-42.<\/jats:p>","DOI":"10.3390\/jcm11195632","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T01:41:58Z","timestamp":1664156518000},"page":"5632","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Efficacy and Safety of Tinzaparin in Prophylactic, Intermediate and Therapeutic Doses in Non-Critically Ill Patients Hospitalized with COVID-19: The PROTHROMCOVID Randomized Controlled Trial"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9774-963X","authenticated-orcid":false,"given":"Nuria","family":"Mu\u00f1oz-Rivas","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain"},{"name":"Universidad Complutense, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5415-3449","authenticated-orcid":false,"given":"Jes\u00fas","family":"Aibar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Cl\u00ednic, IDIBAPS, 08036 Barcelona, Spain"},{"name":"University of Barcelona, 08007 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Gabara-Xanc\u00f3","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Cl\u00ednic, IDIBAPS, 08036 Barcelona, Spain"},{"name":"University of Barcelona, 08007 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngela","family":"Trueba-Vicente","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital de Emergencias Enfermera Isabel Zendal, 28055 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7468-7077","authenticated-orcid":false,"given":"Ana","family":"Urbelz-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital de Emergencias Enfermera Isabel Zendal, 28055 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"G\u00f3mez-Del Olmo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3096-4711","authenticated-orcid":false,"given":"Pablo","family":"Demelo-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8600-1183","authenticated-orcid":false,"given":"Alberto","family":"Rivera-Gallego","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital \u00c1lvaro Cunqueiro, 36312 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7435-1829","authenticated-orcid":false,"given":"Pau","family":"Bosch-Nicolau","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hospital Universitario Vall d\u2019Hebron, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3683-5478","authenticated-orcid":false,"given":"Montserrat","family":"Perez-Pinar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Virgen de la Luz, 16002 Cuenca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Rios-Prego","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Complexo Hospitalario Universitario de Pontevedra, 36071 Pontevedra, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Madridano-Cobo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario Infanta Sof\u00eda, 28702 San Sebasti\u00e1n de los Reyes, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ramos-Alonso","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario A Coru\u00f1a, 15006 A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4910-1497","authenticated-orcid":false,"given":"Jes\u00fas","family":"Alonso-Carrillo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iria","family":"Francisco-Albelsa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitari de Girona Dr. Josep Trueta, 17007 Girona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edelmira","family":"Mart\u00ed-Saez","sequence":"additional","affiliation":[{"name":"Department of Haematology, Hospital Cl\u00ednico Universitario de Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Maestre-Peir\u00f3","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario de Vinalop\u00f3, 03293 Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"M\u00e9ndez-Bail\u00f3n","sequence":"additional","affiliation":[{"name":"Universidad Complutense, 28040 Madrid, Spain"},{"name":"Department of Internal Medicine, Hospital Clinico San Carlos, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4550-757X","authenticated-orcid":false,"given":"Jos\u00e9 \u00c1ngel","family":"Hern\u00e1ndez-Rivas","sequence":"additional","affiliation":[{"name":"Universidad Complutense, 28040 Madrid, Spain"},{"name":"Department of Hematology, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Torres-Macho","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital Universitario Infanta Leonor, 28031 Madrid, Spain"},{"name":"Universidad Complutense, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/S0140-6736(21)02796-3","article-title":"COVID-19 Excess Mortality Collaborators. 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