Patients with COVID-19 associated ARDS and mechanical ventilation have a high mortality. Part of the disease is an activation of the coagulation system which seems to contribute to clotformation in the pulmonary bloodstream. Recently we implemented an algorithm applying higher doses of heparins (LMWH). However, this approach could not inhibit clotformation enough. Bivalirudin could prevent clotformation better and support dissolving existing clots. Therefore, we want to compare 50 patients with the standard treatment with 50 patients under bivalirudin treatment which we normally apply in patients with a HIT-syndrome. Our primary outcome measure is oxygenation reflected as P/F ratio.
The pandemic of COVID-19, a newly upcoming viral disease caused by SARS-CoV-2, puts the whole
worlds health system under pressure.
Patients suffering from this disease mainly develop respiratory symptoms, which can lead to
severe acute respiratory distress syndrome (ARDS) necessitating ICU admission in 10-20% of
the cases admitted to hospital. In addition to these symptoms, patients show lymphopenia,
cardiac symptoms and altered coagulation profiles. Although those patients are treated in the
ICU the mortality there is more than 20% due to multiorgan failure.
One of the recent insights in this disease is its effect on the coagulation system. Meanwhile
we know that the coagulation system gets activated. Furthermore, it seems that clot formation
takes place in the pulmonary micro-vasculature which could contribute to the widely observed
gas-exchange impairment. Therefore, many centers apply empiric anticoagulation for their
COVID-patients. At the moment, we at HMC, also apply an empirical anticoagulation protocol as
our standard approach. However, this is a symptomatic treatment without good proof.
Bivalirudin is a well-known agent which is used in HMC for cases in which anticoagulation is
needed, but a contraindication for heparin exists (i.e. HIT syndrome). This drug has an
interesting pharmacologic profile. It acts independent of antithrombin (AT), the
physiological compound which enhances heparin effects under normal circumstances. This lack
of dependence on AT, makes Bivalirudin an attractive choice in light of the contradictory
reports on the levels of AT during COVID infection. If AT levels are decreased during the
infection, heparin (as well as LMWH) cannot work efficiently, which would render our
treatment less effective. Luckily, bivalirudin acts without the support of AT, so we could
bypass this problem. In addition, bivalirudin has some fibrinolytic activities. It inhibits
clot-bound thrombin which as a result destabilizes the clot rendering it more susceptible to
thrombolysis. This property partially supports the dissolving of clots and could support
re-opening the pulmonary microcirculation.
Objectives:
To prove the positive effect of anticoagulation with bivalirudin intravenously on
gas-exchange in patients with COVID-19 and respiratory failure on invasive mechanical
ventilation.
Drug: Bivalirudin Injection
The patients will receive iv Bivalirudin according to the institutional HIT protocol.
Other Name: anticoagulation
Drug: Standard treatment
This group will receive standard anticoagulation with LMWH/UFH
Inclusion Criteria:
- Adult patient (≥ 18 years of age)
- Positive COVID-test
- Under mechanical ventilation
- D-Dimers>1.2 mg/L
Exclusion Criteria:
- Pregnancy
- Allergy to the drug (bivalirudin)
- Inherited coagulation abnormalities
- No informed consent
Hamad Medical Corporation
Doha, Qatar
Investigator: Nadir Kharma, MD
Contact: 00974
nkharma@hamad.qa
Marcus Lance, MD, PhD
00974 - 33530292
mlance@hamad.qa
Stefan Roehrig, MD, MBA
00974 - 66030924
srohrig@hamad.qa
Marcus Lance, MD, PhD, Principal Investigator
HMC