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Clinical Trial
. 2023 Oct 24;23(1):718.
doi: 10.1186/s12879-023-08297-7.

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

B Cosmi  1   2 , M Giannella  3 , G Fornaro  4 , F Cristini  5 , A Patacca  5 , A Castagna  6 , F Mazzaferri  7 , S Testa  8 , A Pan  9 , M Lupi  9 , P Brambilla  9 , A Montineri  10 , S Frattima  11 , E G Bignami  12 , M Salvetti  13 , G De Stefano  14 , E Grandone  15   16 , G Di Perri  17 , R Rozzini  18 , A Stella  19 , A Romagnoli  20 , F Drago  21 , P Viale  3
Affiliations
Clinical Trial

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

B Cosmi et al. BMC Infect Dis. .

Abstract

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.

Keywords: COVID-19; Enoxaparin; Major bleeding; Thromboprofilaxis; Venous thromboembolism.

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Conflict of interest statement

B. Cosmi received speakers honoraria by Sanofi, Werfen IL, fees for advisory board from Viatris and Techdow Pharma Italy; E. Grandone received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Sanofi, ItalFarmaco, Rovi, Stago Werfen; A. Castagna received consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events and participated to Data Safety Monitoring Board or Advisory Board from MSD, Gilead Sciences, Jannsen Cilag and Viiv Healthcare and Theratechnologies; A. Stella received consulting fees from Techdow Pharma Italy; A. Romagnoli is employed by Ricerche Nuove Pisa, Italy and received Contract from Techdow Italy Srl for the INHIXACOVID19 Study Management. Other authors declare no known competing financial interest or personal relationship that could have appeared influence the study.

Figures

Fig. 1
Fig. 1
Consort flow diagram illustrating progress of patients throw the study
Fig. 2
Fig. 2
Length of hospital days in patients in the interventional and observation cohort after propensity-score matching
See this image and copyright information in PMC

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