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

• Status: Recruiting
• Trial end date: 2021-07-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Massimo Girardis
• Treatments: Calcium heparin; Enoxaparin; Heparin; Methylprednisolone; Methylprednisolone Hemisuccinate

Criteria

Inclusion Criteria:

1. Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material)

2. Positive pressure ventilation (either non-invasive or invasive) from > 24 hours

3. Invasive mechanical ventilation from < 96 hours

4. P/F ratio < 150

5. D-dimer level > 6 x upper limit of local reference range

6. PCR > 6 fold upper limit of local reference range

Exclusion Criteria:

1. Age < 18 years

2. On-going treatment with anticoagulant drugs

3. Platelet count <100.000/mmc

4. History of heparin-induced thrombocytopenia

5. Allergy to sodium enoxaparine or other LMWH, unfractionated heparin or metylprednisolone;

6. Active bleeding or on-going clinical condition deemed at high risk of bleeding contraindicating anticoagulant treatment

7. Recent (in the last 1 month prior to randomization) brain, spinal or ophthalmic surgery

8. Chronic assumption or oral corticosteroids

9. Pregnancy or breastfeeding or positive pregnancy test. In childbearing age women, before inclusion, a pregnancy test will be performed if not available;

10. Clinical decision to withhold life-sustaining treatment or "too sick to benefit";

11. Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition);

12. Lack or withdrawal of informed consent.