Steroids and Unfractionated Heparin in Critically Ill Patients With Pneumonia From COVID-19 Infection

Summary

SARS-CoV-2 infection seems to induce in most critical cases an excessive and aberrant hyper-inflammatory host immune response that is associated with a so-called "cytokine storm", moreover pro-thrombotic derangements of haemostatic system is another common finding in most severe forms of COVID19 infections, which may be explained by the activation of coagulative cascade primed by inflammatory stimuli, in line with what is observed in many other forms of sepsis. Targeting inflammatory responses exploiting steroids' anti-inflammatory activity along with thrombosis prevention may be a promising therapeutic option to improve patients' outcome. Despite the biological plausibility, no good evidence is available on the efficacy and safety of heparin on sepsis patients, and many issues have to be addressed, regarding the proper timing, dosages and administration schedules of anticoagulant drugs. The primary objective is to assess the hypothesis that an adjunctive therapy with steroids and unfractionated heparin (UFH) or with steroids and low molecular weight heparin (LMWH) are more effective in reducing any-cause mortality in critically-ill patients with pneumonia from COVID- 19 infection compared to low molecular weight heparin (LMWH) alone. Mortality will be measured at 28 days. The study is designed as a multicenter, national, interventional, randomized, investigator sponsored, three arms study. Patients, who satisfy all inclusion criteria and no exclusion criteria, will be randomly assigned in a ratio 1:1:1 to one of the three treatment groups: LMWH group, LMWH+steroids or UFH+steroid group. A possible result showing the efficacy of the composite treatment in reducing the mortality rate among critically ill patients with pneumonia from COVID-19 infection will lead to a revision of the current clinical approach to this disease.

Conditions

• Covid19
• SARS-CoV Infection
• Pneumonia, Viral
• Coagulopathy

Interventions

DRUG

Enoxaparin

Enoxaparin will be administered subcutaneously at standard prophylactic dose (i.e., 4000 UI once day, increased to 6000 UI once day for patients weighting more than 90 kg). The treatment will be administered daily up to ICU discharge. After ICU discharge it may be continued or interrupted in the destination ward up to clinical judgement of the attending physician.

DRUG

Methylprednisolone

Methylprednisolone will be administered intravenously with an initial bolus of 0,5 mg/kg followed by administration of 0,5 mg/kg 4 times daily for 7 days, 0,5 mg/kg 3 times daily from day 8 to day 10, 0,5 mg/kg 2 times daily at days 11 and 12 and 0,5 mg/kg once daily at days 13 and 14.

DRUG

unfractionated heparin

Patients in this group will receive unfractionated heparin and methylprednisolone. Unfractionated heparin will be administered intravenously at therapeutic doses. The infusion will be started at an infusion rate of 18 IU/kg/hour and then modified to attain APTT Ratio in the range 1.5-2.0. aPTT will be periodically checked at intervals no longer than 12 hours. The treatment with unfractionated heparin will be administered up to ICU discharge. After ICU discharge anticoagulant therapy may be interrupted or switched to prophylaxis with LMWH in the destination ward up to clinical judgement of the attending physician.

Sponsors & Collaborators

• Massimo Girardis

  lead OTHER

Principal Investigators

• Massimo Girardis, PI · University of Modena and Reggio Emilia

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-11-25

Primary Completion

2021-06-30

Completion

2021-07-30

Countries

• Italy

Study Locations