Intermediate dose enoxaparin in hospitalized patients with moderate-severe COVID-19: a pilot phase II single-arm study, INHIXACOVID19.

Autor: Cosmi B; Angiology and Blood Coagulation Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni, 15, Bologna, Italy. benilde.cosmi@unibo.it.; Angiology and Blood Coagulation Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. benilde.cosmi@unibo.it., Giannella M; Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola IRCSS, University of Bologna, Via Massarenti 11, Bologna, 40138, Italy., Fornaro G; Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola IRCSS, University of Bologna, Via Massarenti 11, Bologna, 40138, Italy. giacomofornaro1990@gmail.com., Cristini F; Infectious Disease Unit, Forlì and Cesena Hospiitals, Forlì-Cesena, Italy., Patacca A; Infectious Disease Unit, Forlì and Cesena Hospiitals, Forlì-Cesena, Italy., Castagna A; Clinica di Malattie Infettive, Università Vita-Salute, IRCCS San Raffaele Hospital, Milan, Italy., Mazzaferri F; Division of Infectious Diseases, Department of Medicine, Verona University Hospital, Verona, Italy., Testa S; Haemostasis and Thrombosis Center, ASST Cremona, Cremona, Italy., Pan A; Infectious Disease Unit, ASST Cremona, Cremona, Italy., Lupi M; Infectious Disease Unit, ASST Cremona, Cremona, Italy., Brambilla P; Infectious Disease Unit, ASST Cremona, Cremona, Italy., Montineri A; San Marco Hospital, Catania, Italy., Frattima S; Carlo Poma Hospital, Mantua, Italy., Bignami EG; Anesthesiology, Critical Care and Pain Medicine Division, Department of Medicine and Surgery, University of Parma, Parma, Italy., Salvetti M; ASST Spedali Civili di Brescia and University of Brescia, Brescia, Italy., De Stefano G; San Carlo Hospital Potenza, Potenza, Italy., Grandone E; Fondazione 'Casa Sollievo della Sofferenza' San Giovanni Rotondo, Department Medical and Surgical Sciences, University of Foggia, Foggia, Italy.; Ob/Gyn First Sechenov University, Moscow, Russia., Di Perri G; Amedeo di Savoia Hospital, Turin, Italy., Rozzini R; Dipartimento di Geraitria, Unità di cura subintensiva- Unità di Geriatria per Acuti, Unità di attività subacute,Poliambulanza Hospital, Brescia, Italy., Stella A; Department of Speciality Diagnostics and Experimental Medicine (DIMES), Sant'Orsola Hospital University of Bologna, Bologna, Italy., Romagnoli A; Ricerche Nuove, Pisa, Italy., Drago F; University of Catania (UNICT), Catania, Italy., Viale P; Infectious Diseases Unit, Department of Medical and Surgical Sciences, Policlinico Sant'Orsola IRCSS, University of Bologna, Via Massarenti 11, Bologna, 40138, Italy.
Jazyk: angličtina
Zdroj: BMC infectious diseases [BMC Infect Dis] 2023 Oct 24; Vol. 23 (1), pp. 718. Date of Electronic Publication: 2023 Oct 24.
DOI: 10.1186/s12879-023-08297-7
Abstrakt: Background: Randomized clinical trials in non-critically ill COVID-19 patients showed that therapeutic-dose heparin increased survival with reduced organ support as compared with usual-care thromboprophylaxis, albeit with increased bleeding risk. The purpose of the study is to assess the safety of intermediate dose enoxaparin in hospitalized patients with moderate to severe COVID-19.
Methods: A phase II single-arm interventional prospective study including patients receiving intermediate dose enoxaparin once daily according to body weight: 60 mg for 45-60 kg, 80 mg for 61-100 kg or 100 mg for > 100 kg for 14 days, with dose adjustment according to anti-factor Xa activity (target range: 0.4-0.6 UI/ml); an observational cohort (OC) included patients receiving enoxaparin 40 mg day for comparison. Follow-up was 90 days. Primary outcome was major bleeding within 30 and 90 days after treatment onset. Secondary outcome was the composite of all-cause 30 and 90-day mortality rates, disease severity at the end of treatment, intensive care unit (ICU) admission and length of ICU stay, length of hospitalization. All outcomes were adjudicated by an independent committee and analyzed before and after propensity score matching (PSm).
Results: Major bleeding was similar in IC (1/98 1.02%) and in the OC (none), with only one event observed in a patient receiving concomitantly anti-platelet therapy. The composite outcome was observed in 53/98 patients (54%) in the IC and 132/203 (65%) patients in the OC (p = 0.07) before PSm, while it was observed in 50/90 patients (55.6%) in the IC and in 56/90 patients (62.2%) in the OC after PSm (p = 0.45). Length of hospitalization was lower in the IC than in OC [median 13 (IQR 8-16) vs 14 (11-21) days, p = 0.001], however it lost statistical significance after PSm (p = 0.08). At 30 days, two patients had venous thrombosis and two pulmonary embolism in the OC. Time to first negative RT-PCR were similar in the two groups.
Conclusions: Weight adjusted intermediate dose heparin with anti-FXa monitoring is safe with potential positive impact on clinical course in COVID-19 non-critically ill patients.
Trial Registration: The study INHIXACOVID19 was registred on ClinicalTrials.gov with the trial registration number (TRN) NCT04427098 on 11/06/2020.
(© 2023. BioMed Central Ltd., part of Springer Nature.)
Databáze: MEDLINE
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